Application of the metal ions as potential population biomarkers for wastewater-based epidemiology: estimating tobacco consumption in Southern China.

Wastewater-based epidemiology (WBE) is an objective approach for the estimation of population-level exposure to a wide range of substances, in which the use of a population biomarker (PB) could significantly reduce back-calculation errors. Although some endogenous or exogenous compounds such as cotinine and other hormones have been developed as PBs, more PBs still need to be identified and evaluated. This study aimed to propose a novel method to estimate population parameters from the mass load of metal ion biomarkers in wastewater, and estimate the consumption of tobacco in 24 cities in Southern China using the developed method. Daily wastewater samples were collected from 234 wastewater treatment plants (WWTPs) in 24 cities in Southern China. Atomic absorption spectroscopy (AAS) was applied to determine the concentrations of common health-related metal ions in wastewater, including sodium (Na), potassium (K), magnesium (Mg), calcium (Ca), iron (Fe), and zinc (Zn), and compared them with the daily mass load of cotinine corresponding to catchment populations. The concentrations of cotinine in wastewater samples were measured using liquid chromatography-tandem mass spectrometry. There were clear and strong correlations between the target metal ion equivalent population and census data. The correlation coefficients (R) were RK = 0.78, RNa = 0.66, RCa = 0.81, RMg = 0.77, and RFe = 0.69, at p < 0.01 and R2 > 0.6. Subsequently, the combination of WBE and metal ion PBs was used to estimate tobacco consumption. Daily consumption of nicotine was estimated to be approximately 1.76 ± 1.19 mg/d/capita, equivalent to an average of 13.0 ± 8.75 cigarettes/d being consumed by smokers. The data on tobacco consumption in this study were consistent with those in traditional surveys in Southern China. The metal ion potassium is an appropriate PB for reflecting the real-time population and could be used to evaluate the tobacco consumption in WBE study.

Impurity profiling of alfentanil hydrochloride by liquid chromatography/quadrupole time-of-flight high-resolution mass spectrometric techniques for drug enforcement.

RATIONALE: Fentanyl and its analogues play important roles in the hospital and clinic setting as anesthetics. However, illicitly manufactured fentanyl as well as the new psychoactive substances (NPS) account for 30% of all deaths in the United States. Since fentanyl derivatives and NPS are designed to produce similar effects, their related substances are similar or even have the same active groups. A comprehensive analysis of the related substances of alfentanil hydrochloride can provide a basis for the identification and supervision of fentanyl derivatives and NPS. METHODS: A liquid chromatography/quadrupole time-of-flight tandem mass spectrometry (LC/QTOF-MS/MS) method was developed for the separation and characterization of related substances in alfentanil hydrochloride. Degradation studies were conducted according to the ICH-prescribed stress conditions. The compounds were identified mainly through positive electrospray ionization QTOF high-resolution mass spectrometric measurements of the accurate masses of the precursor and product ions and their calculated elemental compositions. Their formation mechanisms were also discussed. RESULTS: Seventeen related substances were detected in alfentanil hydrochloride and its stressed samples. Among them, nine were process-related substances and the other eight were degradation products. The stress study results demonstrated that alfentanil hydrochloride was unstable under acid, alkaline, and oxidative stress conditions, while relatively stable under dry photolytic and thermal stress conditions. Alfentanil hydrochloride was most susceptible for degradation at the N-phenylpropanamide and piperidine sites. CONCLUSIONS: Process-related alfentanil hydrochloride compounds are useful for determination of synthetic routes and entangling of fentanyl analogues. The stress study results can provide a sound scientific basis for the waste water monitoring of alfentanil. These results are important for routine quality control in the manufacturing and storage of alfentanil hydrochloride, as well as for drug enforcement of fentanyl and its analogues.

Association of the variants in the BUD13-ZNF259 genes and the risk of hyperlipidaemia.

The single nucleotide polymorphisms (SNPs) in the BUD13 homolog (BUD13) and zinc finger protein 259 (ZNF259) genes have been associated with one or more serum lipid traits in the European populations. However, little is known about such association in the Chinese populations. Our objectives were to determine the association of the BUD13/ZNF259 SNPs and their haplotypes with hypercholesterolaemia (HCH)/hypertriglyceridaemia (HTG) and to identify the possible gene-gene interactions among these SNPs. Genotyping of 6 SNPs was performed in 634 hyperlipidaemic and 547 normolipidaemic participants. The ZNF259 rs2075290, ZNF259 rs964184 and BUD13 rs10790162 SNPs were significantly associated with serum lipid levels in both HCH and non-HCH populations (P < 0.008-0.001). On single locus analysis, only BUD13 rs10790162 was associated with HCH (OR: 2.23, 95% CI: 1.05, 4.75, P = 0.015). The G-G-A-A-C-C haplotype, carrying rs964184-G-allele, was associated with increased risk of HCH (OR: 1.35, 95% CI: 1.10, 1.66, P = 0.005) and HTG (OR: 1.75, 95% CI: 1.39, 2.21, P = 0.000). The A-C-G-G-C-C and A-C-A-G-T-C haplotypes, carrying rs964184-C-allele, were associated with reduced risk of HCH (OR: 0.77, 95% CI: 0.61, 0.99, P = 0.039 and OR: 0.66, 95% CI: 0.47, 0.94, P = 0.021 respectively). On multifactor dimensionality reduction analyses, the two- to three-locus models showed a significant association with HCH and HTG (P < 0.01-0.001). The BUD13/ZNF259 SNPs, which were significant in the European populations, are also replicable in the Southern Chinese population. Moreover, inter-locus interactions may exist among these SNPs. However, further functional studies are required to clarify how these SNPs and genes actually affect the serum lipid levels.

Sex-specific association of the zinc finger protein 259 rs2075290 polymorphism and serum lipid levels.

BACKGROUND: Little is known about the association of ZNF259 rs2075290 single nucleotide polymorphism (SNP) and serum lipid levels in the Chinese population. This study aimed to detect the association of ZNF259 rs2075290 SNP and environmental factors with serum lipid levels between males and females in the Mulao and Han populations. METHODS AND RESULTS: Genotyping of ZNF259 rs2075290 SNP was performed in 788 of Mulao and 778 of Han participants using polymerase chain reaction and restriction fragment length polymorphism. The genotype frequencies were significantly different between Mulao and Han populations (AA, 50.1% Vs 58.9%; AG, 42.3% Vs 35.7%; GG, 7.6% Vs 5.4%, P = 0.002) and between Han males and females (AA, 64.5% Vs 55.2%; AG, 28.3% Vs 40.6%; GG, 7.2% Vs 4.2%, P = 0.001). Serum levels of triglyceride (TG) in Mulao males, and total cholesterol (TC), TG and low-density lipoprotein cholesterol (LDL-C) in Mulao females were different between the AA and AG/GG genotypes (P < 0.05-0.001). Serum TC, LDL-C and apolipoprotein (Apo) A1 levels in Han males, and TG and ApoB levels and ApoA1/ApoB ratio in Han females were different between the AA and AG/GG genotypes (P < 0.05-0.001). An interaction between ZNF259 rs2075290 polymorphism and male gender on serum TC, LDL-C, and ApoA1 levels was noted in Han population (P < 0.05-0.01) but not in Mulao's. CONCLUSIONS: The subjects with AG/GG genotype in Mulao males and females and Han females have less favorable lipid profiles than those with AA genotype. In contrast, the subjects with AG/GG genotype in Han males have more favorable lipid profiles than those with AA genotype. These findings suggest that the association between ZNF259 rs2075290 SNP and serum lipid levels might have ethnic- and/or sex-specificity.

Association between single nucleotide polymorphism rs1044925 and the risk of coronary artery disease and ischemic stroke.

The present study was performed to clarify the association between the acyl-CoA:cholesterol acyltransferase-1 (ACAT-1) single nucleotide polymorphism (SNP) rs1044925 and the risk of coronary artery disease (CAD) and ischemic stroke (IS) in the Guangxi Han population. Polymerase chain reaction and restriction fragment length polymorphism was performed to determine the genotypes of the ACAT-1 SNP rs1044925 in 1730 unrelated subjects (CAD, 587; IS, 555; and healthy controls; 588). The genotypic and allelic frequencies of rs1044925 were significantly different between the CAD patients and controls (p = 0.015) and borderline different between the IS patients and controls (p = 0.05). The AC/CC genotypes and C allele were associated with a decreased risk of CAD and IS (CAD: p = 0.014 for AC/CC vs. AA, p = 0.022 for C vs. A; IS: p = 0.014 for AC/CC vs. AA; p = 0.017 for C vs. A). The AC/CC genotypes in the healthy controls, but not in CAD or IS patients, were associated with an increased serum high-density lipoprotein cholesterol (HDL-C) concentration. The present study shows that the C allele carriers of ACAT-1 rs1044925 were associated with an increased serum HDL-C level in the healthy controls and decreased risk in CAD and IS patients.

Homocysteine, hyperhomocysteinemia, and H-type hypertension.

Homocysteine (Hcy) is a sulphur-containing nonessential amino acid derived from the intermediate metabolites of methionine. Methionine is obtained from dietary proteins, such as poultry, meat, eggs, seafood, and dairy products. Abnormalities in Hcy metabolic pathways, deficiencies in dietary methionine, folate, and vitamins B12, B6, and B2 and genetic defects, polymorphisms, or mutations in Hcy metabolism-related enzymes may lead to an increase in plasma Hcy levels. Generally, a plasma Hcy level higher than 10 or 15 µmol/L has been defined as hyperhomocysteinemia (HHcy). An individual with essential hypertension complicated with HHcy is considered to have H-type hypertension (HTH). Currently, HHcy is considered a novel independent risk factor for various cardiovascular diseases. To provide a useful reference for clinicians, the research progress on Hcy, HHcy, and HTH in recent years was systematically reviewed here, with a focus on the source and metabolic pathways of Hcy, plasma Hcy levels and influencing factors, detection methods for plasma Hcy levels, relationship between Hcy concentration and hypertension, pathogenesis of HTH, cardiovascular complications of HTH, and treatment of HTH.

Association of the apolipoprotein M gene polymorphisms and serum lipid levels.

The association of rs707921 and rs707922 SNPs in the apolipoprotein M (APOM) gene and serum lipid levels is still controversial. This study aimed to detect the association of the APOM rs707921 and rs707922 SNPs and several environmental factors with serum lipid profiles. Genotyping of rs707921 and rs707922 was performed in 703 of Mulao's and 707 of Han's participants. The serum levels of TG in Mulao, and TG and HDL-C in Han were different between the A and C allele carriers of rs707921 (P < 0.05-0.01); while the serum levels of TG in both Mulao and Han were different between the T and G allele carriers of rs707922 (P < 0.05-0.01). According to the gender-subgroup analysis, the levels of TC in Mulao females, TG and ApoB in Han males, and HDL-C in Han females were associated with the genotypes of rs707921 (P < 0.05 for each); whereas the levels of TG in Mulao males, and TG and ApoB in Han males were correlated with the genotypes of rs707922 (P < 0.05 for each). Serum lipid parameters were also associated with several environmental factors (P < 0.05-0.001). The APOM gene rs707921 and rs707922 SNPs are associated with some serum lipid parameters in the two ethnic groups, but the trends of association suggest that the two SNPs might have racial/ethnic- and/or gender- specificity.

Proprotein convertase subtilisin/kexin type 9 gene E670G polymorphism interacts with alcohol consumption to modulate serum lipid levels.

BACKGROUND: Both alcohol consumption and the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene polymorphism modulate serum lipid levels, but their interactions on serum lipid profiles are still unknown. The present study was undertaken to detect the interactions of PCSK9 E670G polymorphism and alcohol consumption on serum lipid levels. METHODS: Genotypes of the PCSK9 E670G in 1352 unrelated subjects (785 non-drinkers and 567 drinkers) were determined by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing. The interactions between PCSK9 E670G genotypes and alcohol consumption on serum lipid parameters were detected by using a factorial design covariance analysis after controlling for potential confounders. RESULTS: The levels of serum triglyceride, high-density lipoprotein cholesterol, apolipoprotein (Apo) A1, and the ratio of ApoA1 to ApoB were higher in drinkers than in non-drinkers (P < 0.01 for all), whereas the levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and ApoB were lower in drinkers than in non-drinkers (P < 0.001 for all). The genotypic and allelic frequencies of PCSK9 E670G were not different between non-drinkers and drinkers (P > 0.05 for each). The subjects with AA genotype in non-drinkers had higher serum LDL-C levels than the subjects with AG genotype, whereas the subjects with AG genotype in drinkers had higher serum TC levels than the subjects with AA genotypes (P < 0.05 for each). The effects of alcohol consumption on TC and LDL-C levels depended upon genotypes, the subjects with AA genotype had lower serum TC and LDL-C levels in drinkers than in non-drinkers. CONCLUSIONS: Alcohol consumption can modify the effects of the PCSK9 E670G polymorphism on serum TC and LDL-C levels. The subjects with AA genotype of the PCSK9 E670G benefit more from alcohol consumption than the subjects with AG genotype in decreasing serum TC and LDL-C levels.

Scavenger receptor class B type 1 gene rs5888 single nucleotide polymorphism and the risk of coronary artery disease and ischemic stroke: a case-control study.

BACKGROUND: Our previous studies have showed that the rs5888 single nucleotide polymorphism (SNP) in Scavenger receptor class B type 1 (SCARB1) gene is associated with serum lipid levels in the general Chinese populations. The present study was undertaken to detect the associations between rs5888 SNP and the risk of coronary artery disease (CAD) and ischemic stroke (IS). METHODS: A total of 1,716 unrelated subjects (CAD, 601; IS, 533; and healthy controls, 582) were included in this study. Genotyping of the rs5888 SNP were determined by polymerase chain reaction and restriction fragment length polymorphism. RESULTS: The genotypic frequencies of SCARB1 rs5888 SNP were different between CAD patients and controls, the subjects with TT genotype had high risk of CAD (OR = 1.76, P = 0.038 for TT vs. CC; and OR = 1.75, P = 0.036 for TT vs. CC/CT). There was no significant association between genotypes and the risk of IS. Further analysis showed that the subjects with TT genotype in the total population had lower levels of high-density lipoprotein cholesterol than the subjects with CC/CT genotypes (P < 0.05), the subjects with TT genotype in controls but not in CAD or IS patients had higher levels of serum LDL-C and ApoB than those with CC genotype (P < 0.05 for each). CONCLUSIONS: The present study suggests that the SCARB1 rs5888 SNP influences serum lipid levels, and is associated with the risk of CAD.

Several genetic polymorphisms interact with overweight/obesity to influence serum lipid levels.

BACKGROUND: Information about the interactions of single nucleotide polymorphisms (SNPs) and overweight/obesity on serum lipid profiles is still scarce. The present study was undertaken to detect ten SNPs and their interactions with overweight/obesity on serum lipid levels. METHODS: A total of 978 normal weight and 751 overweight/obese subjects of Bai Ku Yao were randomly selected from our previous stratified randomized cluster samples. Normal weight, overweight and obesity were defined as a body mass index (BMI) < 24, 24-28, and > 28 kg/m(2); respectively. Serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein (Apo) A1 and ApoB levels were measured. Genotyping of ATP-binding cassette transporter A1 (ABCA-1) V825I, acyl-CoA:cholesterol acyltransferase-1 (ACAT-1) rs1044925, low density lipoprotein receptor (LDL-R) AvaII, hepatic lipase gene (LIPC) -250G>A, endothelial lipase gene (LIPG) 584C>T, methylenetetrahydrofolate reductase (MTHFR) 677C>T, the E3 ubiquitin ligase myosin regulatory light chain-interacting protein (MYLIP) rs3757354, proprotein convertase subtilisin-like kexin type 9 (PCSK9) E670G, peroxisome proliferator-activated receptor delta (PPARD) +294T>C, and Scavenger receptor class B type 1 (SCARB1) rs5888 was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing. The interactions were detected by factorial design covariance analysis. RESULTS: The genotypic and allelic frequencies of LIPC and PCSK9 were different between normal weight and overweight/obese subjects, the genotypic frequency of LIPG and allelic frequency of MYLIP were also different between normal weight and overweight/obese subjects (P < 0.05-0.001). The levels of TC, ApoA1 (ABCA-1); TC, LDL-C, ApoA1, ApoB and ApoA1/ApoB (LIPC); TG, HDL-C, and ApoA1 (LIPG); TC, HDL-C, LDL-C, ApoA1 and ApoB (MTHFR); HDL-C and ApoA1 (MYLIP) in normal weight subjects were different among the genotypes (P < 0.01-0.001). The levels of LDL-C, ApoB and ApoA1/ApoB (ABCA-1); HDL-C, ApoA1, ApoB and ApoA1/ApoB (LIPC); TC, HDL-C, ApoA1 and ApoB (LIPG); TC, TG, HDL-C, LDL-C, ApoA1 and ApoB (MTHFR); TC, TG and ApoB (MYLIP); TG (PCSK9); TG, ApoA1 and ApoB (PPARD); and TC, HDL-C, LDL-C, ApoA1 and ApoB (SCARB1) in overweight/obese subjects were different among the genotypes (P < 0.01-0.001). The SNPs of ABCA-1 (LDL-C and ApoA1/ApoB); LIPC (TC, LDL-C, ApoA1 and ApoB); LIPG (ApoB); MTHFR (TC, TG and LDL-C); MYLIP (TC and TG); PCSK9 (TG, HDL-C, ApoB and ApoA1/ApoB); PPARD (TG and ApoA1/ApoB); and SCARB1 (TG, ApoA1 and ApoB) interacted with overweight/obesity to influence serum lipid levels (P < 0.05-0.001). CONCLUSIONS: The differences in serum lipid levels between normal weight and overweight/obese subjects might partly result from different genetic polymorphisms and the interactions between several SNPs and overweight/obesity.

The SCARB1 rs5888 SNP and serum lipid levels in the Guangxi Mulao and Han populations.

BACKGROUND: The associations of scavenger receptor class B type 1 (SCARB1) rs5888 single nucleotide polymorphism (SNP) and serum lipid levels are inconsistant among diverse ethnic populations. The present study was undertaken to detect the association of rs5888 SNP and serum lipid levels in the Guangxi Mulao and Han populations. METHODS: Genotypes of the SCARB1 rs5888 SNP in 801 subjects of Mulao and 807 subjects of Han Chinese were determined by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing. RESULTS: Serum apolipoprotein (Apo) B levels and the T allelic frequency were higher in Mulao than in Han. Serum high-density lipoprotein cholesterol (HDL-C) levels in Mulao were different among the genotypes, the subjects with TT genotype had lower HDL-C levels than the subjects with CC or CT genotype in female (P < 0.05). For the Han population, serum triglyceride (TG), HDL-C, ApoAI, ApoB levels and the ratio of ApoAI to ApoB in males were different among the genotypes, the T allele carriers had lower serum HDL-C, ApoAI levels and ApoAI/ApoB ratio and higher serum ApoB levels than the T allele noncarriers (P < 0.05 for all), the subjects with TT genotype had higher serum TG levels than the subjects with CC or CT genotype. Serum HDL-C levels in Mulao females and serum HDL-C, ApoAI, ApoB levels and the ApoAI/ApoB ratio in Han males were correlated with genotypes by the multiple linear regression analysis. Serum lipid parameters were also influenced by genotype-environmental interactions in Han but not in Mulao populations. CONCLUSIONS: These results suggest that the rs5888 SNP is associated with serum HDL-C levels in Mulao females, and TG, HDL-C, ApoAI, ApoB levels and the ApoAI/ApoB ratio in Han males. The differences in serum ApoB levels between the two ethnic groups might partially attribute to different SCARB1 genotype-environmental interactions.

Association of MYLIP rs3757354 SNP and several environmental factors with serum lipid levels in the Guangxi Bai Ku Yao and Han populations.

BACKGROUND: The association of rs3757354 single nucleotide polymorphism (SNP) in the E3 ubiquitin ligase myosin regulatory light chain-interacting protein (MYLIP, also known as IDOL) gene and serum lipid levels is not well known in the general population. The present study aimed to detect the association of rs3757354 SNP and several environmental factors with serum lipid levels in the Guangxi Bai Ku Yao and Han populations. METHOD: A total of 627 subjects of Bai Ku Yao minority and 614 participants of Han nationality were randomly selected from our stratified randomized cluster samples. Genotyping of the rs3757354 SNP was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing. RESULTS: The levels of serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein (Apo) AI and ApoB were lower in Bai Ku Yao than in Han (P<0.05-0.001). The frequency of G allele was 49.92% in Bai Ku Yao and 56.27% in Han (P<0.05). The frequencies of AA, GA and GG genotypes were 25.52%, 49.12% and 25.36% in Bai Ku Yao, and 19.87%, 47.72% and 32.41% in Han (P<0.05); respectively. There were no significant differences in the genotypic and allelic frequencies between males and females in both ethnic groups. The levels of HDL-C in Bai Ku Yao were different among the genotypes (P<0.05), the G allele carriers had higher serum HDL-C levels than the G allele noncarriers. The levels TC, HDL-C and ApoAI in Han were different among the genotypes (P<0.05 for all), the participants with GA genotype had lower serum TC, HDL-C and ApoAI levels than the participants with AA genotype. These findings were found only in females but not in males. The levels of TG and HDL-C in Bai Ku Yao were correlated with the genotypes, whereas the levels of TC in Han, and TC, LDL-C in Han females were associated with the genotypes (P<0.05 for all). Serum lipid parameters were also correlated with age, sex, alcohol consumption, cigarette smoking, blood pressure, and body mass index in both ethnic groups (P<0.05-0.001). CONCLUSIONS: The present study suggests that the MYLIP rs3757354 SNP is associated with serum TC, HDL-C and ApoAI levels in the Bai Ku Yao and Han populations. But the association is different between the two ethnic groups.

Sex-specific association of ACAT-1 rs1044925 SNP and serum lipid levels in the hypercholesterolemic subjects.

BACKGROUND: Acyl-CoA:cholesterol acyltransferase (ACAT) is a key enzyme in cellular cholesterol homeostasis and in atherosclerosis. The cellular cholesterol efflux correlated with serum high-density lipoprotein cholesterol (HDL-C) concentrations has shown to be impaired in hyperlipidemic mice. The present study was carried out to clarify the association of ACAT-1 rs1044925 single nucleotide polymorphism (SNP) and serum lipid levels in the hyperlipidemic subjects. METHODS: A total of 821 unrelated subjects (hyperlipidemia, 476; normolipidemia, 345) aged 15-80 were included in the study. Genotyping of the ACAT-1 rs1044925 SNP was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing. RESULTS: There was no significant difference in the genotypic and allelic frequencies of ACAT-1 rs1044925 SNP between the normolipidemic and hyperlipidemic subjects. The levels of total cholesterol (TC), HDL-C and apolipoprotein (Apo) AI in hyperlipidemic subjects were different between the AA and AC/CC genotypes in male but not in female (P < 0.05-0.01), the C allele carriers had higher serum TC, HDL-C and ApoAI levels than the C allele noncarriers. The association of genotypes and serum HDL-C and ApoAI levels in hyperlipidemia was found mainly in the male subjects with hypercholesterolemia but not in those with hypertriglyceridemia. There were no significant differences in serum lipid levels between the AA and AC/CC genotypes in the normolipidemic subjects. CONCLUSIONS: The present study shows that the C allele carriers of ACAT-1 rs1044925 SNP in male hyperlipidemic subjects had higher serum TC, HDL-C and ApoAI levels than the C allele noncarriers. There is a sex (male)-specific association of ACAT-1 rs1044925 SNP and serum HDL-C and ApoAI levels in the hypercholesterolemic subjects.

Association of rs2072183 SNP and serum lipid levels in the Mulao and Han populations.

BACKGROUND: Niemann-pick C1-like 1 (NPC1L1) is a key protein for intestinal cholesterol transportation. Common single nucleotide polymorphisms (SNPs) in the NPC1L1 gene have been associated with cholesterol absorption and serum lipid levels. The present study was undertaken to explore the possible association of NPC1L1 rs2072183 1735 C > G SNP and several environmental factors with serum lipid levels in the Mulao and Han populations. METHODS: Genotyping of the rs2072183 SNP was performed in 688 subjects of Mulao and 738 participants of Han Chinese. The interactions between NPC1L1 1735 C > G polymorphism and several environmental factors on serum lipid phenotypes were tested using the factorial design covariance analysis after controlling for potential confounders. RESULTS: The frequency of G allele was lower in Mulao than in Han (29.72% vs. 37.26%, P < 0.001). The frequency of CC, CG and GG genotypes was 49.85%, 40.84% and 9.31% in Mulao, and 39.30%, 46.88% and 13.82% in Han (P < 0.001); respectively. The levels of low-density lipoprotein cholesterol (LDL-C), apolipoprotein (Apo) B and the ratio of ApoAI/ApoB in Han but not in Mulao were different among the three genotypes (P < 0.05 for all), the subjects with GG and CG genotypes had higher LDL-C, ApoB levels and lower ApoAI/ApoB ratio than the subjects with CC genotype. Subgroup analysis showed that the G allele carriers in Han had higher total cholesterol (TC), LDL-C and ApoB levels in males (P < 0.05) and lower ApoAI/ApoB ratio in both sexes (P < 0.05) than the G allele noncarriers. The G allele carriers in Mulao had higher TC and LDL-C levels in males (P < 0.05) and lower high-density lipoprotein cholesterol (HDL-C) levels in both sexes (P < 0.05) than the G allele noncarriers. Serum TC, LDL-C, ApoB levels and ApoAI/ApoB ratio were correlated with genotypes in Han males (P < 0.05) but not in females. Serum lipid parameters were also correlated with several environmental factors. The genotypes of rs2072183 SNP were interacted with gender or cigarette smoking to influence serum TC and HDL-C levels in Mulao, whereas the genotypes of rs2072183 SNP were interacted with several environmental factors to influence all seven lipid traits in Han (P < 0.05-0.01). CONCLUSIONS: The present study suggests that the rs2072183 SNP in NPC1L1 gene and its association with serum lipid profiles are different between the Mulao and Han populations. The difference in serum lipid profiles between the two ethnic groups might partly result from different rs2072183 SNP or NPC1L1 gene-environmental interactions.

Association of rs5888 SNP in the scavenger receptor class B type 1 gene and serum lipid levels.

BACKGROUND: Bai Ku Yao is a special subgroup of the Yao minority in China. The present study was undertaken to detect the association of rs5888 single nucleotide polymorphism (SNP) in the scavenger receptor class B type 1 (SCARB1) gene and several environmental factors with serum lipid levels in the Guangxi Bai Ku Yao and Han populations. METHODS: A total of 598 subjects of Bai Ku Yao and 585 subjects of Han Chinese were randomly selected from our stratified randomized cluster samples. Genotypes of the SCARB1 rs5888 SNP were determined by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing. RESULTS: The levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein (Apo) AI were lower but ApoB was higher in Bai Ku Yao than in Han (P < 0.05-0.001). The frequencies of C and T alleles were 78.3% and 21.7% in Bai Ku Yao, and 73.7% and 26.3% in Han (P < 0.01); respectively. The frequencies of CC, CT and TT genotypes were 60.0%, 36.6% and 3.4% in Bai Ku Yao, and 54.2%, 39.0% and 6.8% in Han (P < 0.01); respectively. The subjects with TT genotype in both ethnic groups had lower HDL-C and ApoAI levels than the subjects with CC or CT genotype (P < 0.05 for all). Subgroup analyses showed that the subjects with TT genotype in Bai Ku Yao had lower HDL-C and ApoAI levels in males than the subjects with CC or CT genotype (P < 0.05 for all), and the T allele carriers had higher TC, LDL-C and ApoB levels in females than the T allele noncarriers (P < 0.05 for all). The participants with TT genotype in Han also had a lower tendency of HDL-C and ApoAI levels in males than the participants with CC or CT genotype, but the difference did not reach statistically significant (P = 0.063 and P = 0.086; respectively). The association of serum HDL-C and ApoAI levels and genotypes was confirmed by the multiple linear regression analysis in both ethnic groups. Serum lipid parameters were also correlated with several environmental factors. CONCLUSIONS: The differences in serum lipid levels between the two ethnic groups might partially attribute to the differences in the SCARB1 rs5888 SNP and several environmental factors.

Several lipid-related gene polymorphisms interact with overweight/obesity to modulate blood pressure levels.

Little is known about the interactions of single nucleotide polymorphisms (SNPs) and overweight/obesity on blood pressure levels. The present study was undertaken to detect 10 lipid-related gene SNPs and their interactions with overweight/obesity on blood pressure levels. Genotyping of ATP-binding cassette transporter A1 (ABCA-1) V825I, acyl-CoA:cholesterol acyltransferase-1 (ACAT-1) rs1044925, low density lipoprotein receptor (LDL-R) AvaII hepatic lipase gene (LIPC) -250G > A, endothelial lipase gene (LIPG) 584C > T, methylenetetrahydrofolate reductase (MTHFR) 677C > T, the E3 ubiquitin ligase myosin regulatory light chain-interacting protein (MYLIP) rs3757354, proprotein convertase subtilisin-like kexin type 9 (PCSK9) E670G, peroxisome proliferator-activated receptor delta (PPARD) +294T > C, and Scavenger receptor class B type 1 (SCARB1) rs5888 was performed in 978 normal weight and 751 overweight/obese subjects. The interactions were detected by factorial regression analysis. The genotypes of ACAT-1 AC, LIPC GA and AA, and SCARB1 TT; LDL-R A-A- and LIPC GA; and SCARB1 TT were interacted with overweight/obesity to increase systolic, diastolic blood pressure (SBP, DBP) and pulse pressure (PP) levels; respectively. The genotypes of ACAT-1 CC; ACAT-1 AA and CC were interacted with overweight/obesity to decrease SBP, PP levels (p < 0.01-0.001); respectively. The differences in blood pressure levels between normal weight and overweight/obese subjects might partly result from different interactions of several SNPs and overweight/obesity.

Differential effects of hyperhomocysteinemia on the lipid profiles and lipid ratios between patients with and without coronary artery disease: A retrospective observational study.

This study aimed to investigate the differential effects of hyperhomocysteinemia (HHcy) on lipid profiles and lipid ratios between patients with coronary artery disease (CAD) and without CAD. The data of 872 CAD patients and 774 non-CAD controls were extracted from the information system of hospitalized patients. Serum homocysteine (Hcy), total cholesterol (TC), triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein (Apo) AI, and ApoB concentrations were detected. HHcy was defined as a serum level of Hcy ≥ 15 µmol/L. The CAD patients had lower levels of HDL-C and ApoAI and higher levels of Hcy than the controls (P < .05). Serum TGs and HDL-C were negatively correlated with Hcy in controls. Serum HDL-C and ApoAI were negatively correlated with Hcy, and the ratios of TC/HDL-C, TG/HDL-C, LDL/HDL-C, and ApoB/ApoAI were positively correlated with Hcy in the CAD patients (P < .05). Although the trends for HHcy to decrease the lipid profiles were not different between the CAD and controls (Pinteraction > 0.05), CAD with HHcy had lower HDL-C and ApoAI levels than those of subjects with normal Hcy; controls with HHcy had lower TC, LDL-C, and ApoB levels than those of subjects with normal Hcy (P < .05). There were different HHcy trends affecting the ratios of TC/HDL-C and LDL/HDL-C between the CAD patients and controls (Pinteraction for TC/HDL-C = 0.025; Pinteraction for LDL/HDL-C = 0.033). CAD patients with HHcy had a higher ratio of TC/HDL-C (P = .022) and LDL/HDL-C (P = .045) than those of patients with normal Hcy, but in the controls, the subjects with HHcy exhibited a trend toward a decreased ratio of TC/HDL-C (P = .481) and LDL/HDL-C (P = .303). There were differential effects of HHcy on the lipid ratios between CAD and non-CAD patients. HHcy was related to higher ratios of TC/HDL-C and LDL/HDL-C in patients with CAD.

The peroxisome proliferator-activated receptor delta +294T > C polymorphism and alcohol consumption on serum lipid levels.

BACKGROUND: The single nucleotide polymorphism (SNP) of peroxisome proliferator-activated receptor delta (PPARD) gene affects serum lipid profiles, but to what extent alcohol consumption interferes with this association remains unknown. The present study was undertaken to compare the association of PPARD +294T > C (rs2016520) polymorphism and serum lipid levels in the nondrinkers and drinkers. METHODS: A total of 685 unrelated nondrinkers and 497 drinkers aged 15-82 were randomly selected from our previous stratified randomized cluster samples. Genotyping of the PPARD +294T > C was performed by polymerase chain reaction and restriction fragment length polymorphism. Interactions of the PPARD +294T > C genotypes and alcohol consumption on serum lipid levels were detected by using a factorial regression analysis after controlling for potential confounders. RESULTS: The levels of triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), apolipoprotein (Apo) A1, and the ratio of ApoA1 to ApoB were higher in drinkers than in nondrinkers (P < 0.05-0.001). There were no significant differences in the levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and ApoB between the two groups (P > 0.05 for all). The frequencies of TT, TC and CC genotypes were 56.0%, 36.4% and 7.6% in nondrinkers, and 57.2%, 38.0% and 4.8% in drinkers (P > 0.05); respectively. The frequencies of T and C alleles were 74.2% and 25.8% in nondrinkers, and 76.2% and 23.8% in drinkers (P > 0.05); respectively. There was also no significant difference in the genotypic and allelic frequencies between males and females in both groups (P > 0.05 for all). The levels of TC in nondrinkers were different among the three genotypes (P = 0.01), the C allele carriers had higher serum TC levels than the C allele noncarriers. The levels of all seven lipid traits in drinkers were not different among the three genotypes (P > 0.05 for all). The interactions of PPARD +294T > C genotypes and alcohol consumption on serum lipid levels were not detected in the drinkers (P >0.05 for all). Multiple linear regression analysis showed that serum TC, HDL-C, LDL-C, ApoA1, and ApoB levels were correlated with genotypes in drinkers but not in nondrinkers (P < 0.05-0.01). CONCLUSIONS: These results suggest that the great majority of our study populations are beneficial from alcohol consumption. But there is no interaction between the PPARD +294T > C genotypes and alcohol consumption on serum lipid levels in the drinkers.

Genetic variant of V825I in the ATP-binding cassette transporter A1 gene and serum lipid levels in the Guangxi Bai Ku Yao and Han populations.

BACKGROUND: Several genetic variants in the ATP-binding cassette transporter A1 (ABCA1) gene have associated with modifications of serum high-density lipoprotein cholesterol (HDL-C) levels and the susceptibility for coronary heart disease, but the findings are still controversial in diverse racial/ethnic groups. Bai Ku Yao is an isolated subgroup of the Yao minority in southern China. The present study was undertaken to detect the possible association of V825I (rs2066715) polymorphism in the ABCA1 gene and several environmental factors with serum lipid levels in the Guangxi Bai Ku Yao and Han populations. METHODS: A total of 677 subjects of Bai Ku Yao and 646 participants of Han Chinese were randomly selected from our previous stratified randomized cluster samples. Polymerase chain reaction and restriction fragment length polymorphism assay combined with gel electrophoresis were performed for the genotyping of V825I variant, and then confirmed by direct sequencing. RESULTS: The levels of serum total cholesterol (TC), HDL-C, apolipoprotein (Apo) AI and ApoB were lower in Bai Ku Yao than in Han (P < 0.01 for all). The frequency of G and A alleles was 57.4% and 42.6% in Bai Ku Yao, and 57.7% and 42.3% in Han (P > 0.05); respectively. The frequency of GG, GA and AA genotypes was 33.7%, 47.4% and 18.9% in Bai Ku Yao, and 33.4%, 48.6% and 18.0% in Han (P > 0.05); respectively. There was no difference in the genotypic and allelic frequencies between males and females in the both ethnic groups. The subjects with AA genotype in Bai Ku Yao had higher serum TC levels than the subjects with GG and GA genotypes (P < 0.05). The participants with AA genotype in Han had lower serum HDL-C and ApoAI levels than the participants with GG and GA genotypes (P < 0.05 for each), but these results were found in males but not in females. Multivariate linear regression analysis showed that the levels of TC in Bai Ku Yao and HDL-C and ApoAI in male Han were correlated with genotypes (P < 0.05 for all). Serum lipid parameters were also correlated with sex, age, body mass index, alcohol consumption, and blood pressure in both ethnic groups (P < 0.05-0.001). CONCLUSION: The present study suggests that the V825I polymorphism in the ABCA1 gene is associated with male serum HDL-C and ApoAI levels in the Han, and serum TC levels in the Bai Ku Yao populations. The difference in the association of V825I polymorphism and serum lipid levels between the two ethnic groups might partly result from different ABCA1 gene-environmental interactions.

Low density lipoprotein receptor gene Ava II polymorphism and serum lipid levels in the Guangxi Bai Ku Yao and Han populations.

BACKGROUND: Several common genetic polymorphisms in the low density lipoprotein receptor (LDL-R) gene have associated with modifications of serum total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) levels, but the results are not consistent in different populations. Bai Ku Yao is a special subgroup of the Yao minority in China. The present study was undertaken to detect the association of LDL-R gene Ava Ⅱ polymorphism and serum lipid levels in the Guangxi Bai Ku Yao and Han populations. METHODS: A total of 1024 subjects of Bai Ku Yao and 792 participants of Han Chinese were randomly selected from our previous stratified randomized cluster samples. Genotyping of the LDL-R gene Ava Ⅱ polymorphism was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing. RESULTS: The levels of serum TC, high density lipoprotein cholesterol (HDL-C), LDL-C, apolipoprotein (Apo) A1 and the ratio of ApoA1 to ApoB were lower in Bai Ku Yao than in Han (P < 0.01 for all). The frequency of A⁻ and A+ alleles was 65.5% and 34.5% in Bai Ku Yao, and 80.7% and 19.3% in Han (P < 0.001); respectively. The frequency of A⁻A⁻, A⁻A+ and A+A+ genotypes was 42.6%, 45.9% and 11.5% in Bai Ku Yao, and 64.9%, 31.6% and 3.5% in Han (P < 0.001); respectively. There was also significant difference in the genotypic frequencies between males and females in Bai Ku Yao (P <0.05), and in the genotypic and allelic frequencies between normal LDL-C (≤ 3.20 mmol/L) and high LDL-C (> 3.20 mmol/L) subgroups in Bai Ku Yao (P < 0.05 for each) and between males and females in Han (P < 0.05 for each). The levels of LDL-C in males and TC and HDL-C in females were different among the three genotypes (P < 0.05 for all) in Bai Ku Yao, whereas the levels of HDL-C in males and HDL-C and ApoA1 in females were different among the three genotypes (P < 0.05-0.001) in Han. The subjects with A+A+ genotype had higher serum LDL-C, TC, HDL-C or ApoA1 levels than the subjects with A-A+ and A⁻A⁻ genotypes. Spearman rank correlation analysis revealed that the levels of LDL-C in Bai Ku Yao and HDL-C in Han were correlated with genotypes (P < 0.05 and P < 0.01; respectively). CONCLUSIONS: The association of LDL-R gene Ava Ⅱ polymorphism and serum lipid levels is different between the Bai Ku Yao and Han populations. The discrepancy might partly result from different LDL-R gene Ava Ⅱ polymorphism or LDL-R gene-environmental interactions.