TIMD4 rs6882076 SNP Is Associated with Decreased Levels of Triglycerides and the Risk of Coronary Heart Disease and Ischemic Stroke.

Background: The T-cell immunoglobulin and mucin domain 4 gene (TIMD4) rs6882076 single nucleotide polymorphism (SNP) has been associated with serum total cholesterol, low-density lipoprotein cholesterol and triglycerides (TG) levels, but the results are inconsistent. Moreover, little is known about such association in Chinese populations. The aim of this study was to detect the association of the TIMD4 rs6882076 SNP and serum lipid levels and the risk of coronary heart disease (CHD) and ischemic stroke (IS) in a Southern Chinese Han population. Methods: Genotypes of the TIMD4 rs6882076 SNP in 1765 unrelated subjects (CHD, 581; IS, 559 and healthy controls, 625) were determined by the Snapshot Technology. Results: The genotypic and allelic frequencies of the TIMD4 rs6882076 SNP were different between the CHD/IS patients and controls (P < 0.05 for all). The subjects with CT/TT genotypes were associated with decreased risk of CHD (P = 0.014 for CT/TT vs. CC genotypes, P = 0.010 for T vs. C alleles) and IS (P = 0.003 for CT/TT vs. CC genotypes; P = 0.016 for T vs. C alleles). The T allele carriers in healthy controls were also associated with decreased levels of serum TG. Conclusions: The results of the present study suggest that the TIMD4 rs6882076 SNP is associated with decreased risk of CHD and IS in our study population. It is likely to decrease the CHD and IS risk by reducing serum TG levels.

DOCK7-ANGPTL3 SNPs and their haplotypes with serum lipid levels and the risk of coronary artery disease and ischemic stroke.

BACKGROUND: Little is known about the association of the dedicator of cytokinesis 7 (DOCK7 rs1748195) and angiopoietin like 3 (ANGPTL3 rs12563308) single nucleotide polymorphisms (SNPs) and their haplotypes with serum lipid levels and the risk of coronary artery disease (CAD) and ischemic stroke (IS) in the Chinese populations. This study aimed to detect such association in a Southern Chinese Han population. METHODS: This study included 1728 subjects (CAD, 568; IS, 539; and controls, 621). Genotypes of the two SNPs were determined by the Snapshot technology. RESULTS: The genotypic and allelic frequencies of the rs1748195 SNP were different between CAD patients and controls (P < 0.05 for each), the rs1748195G allele frequency was higher in CAD patients than in controls (27.6% vs. 23.6%, P = 0.024). The genotypic frequencies of the rs12563308 SNP were also different between CAD patients and controls (P = 0.021). The rs1748195 SNP was associated with an increased risk of CAD after controlling for potential confounders and Bonferroni correction (P < 0.025 considered statistically significant; Recessive: OR = 1.79, 95% CI = 1.04-3.06, P = 0.017; Log-additive: OR = 1.27, 95% CI = 1.02-1.57, P = 0.014), whereas the rs12563308 SNP was associated with a decreased risk of CAD (Dominant: OR = 0.69, 95% CI = 0.45-0.94, P = 0.011; Log-additive: OR = 0.73, 95% CI = 0.49-0.89, P = 0.009). The rs1748195 SNP was also associated with an increased risk of severity to coronary artery atherosclerosis (Dominant: OR = 1.45, 95% CI = 1.07-2.11, P = 0.017; Log-additive: OR = 1.35, 95% CI = 1.09-1.82, P = 0.013). The interactions of SNP-environment on serum lipid levels and the risk of severity to coronary artery atherosclerosis, CAD and IS were noted. The rs1748195G-rs12563308T haplotype was associated with an increased angiographic severity to coronary artery atherosclerosis (OR = 1.46, 95% CI = 1.05-2.03), and the risk of CAD (OR = 1.37, 95% CI = 1.08-1.74). The interactions of haplotype-hypertension on the risk of CAD and haplotype-drinking on the risk of CAD/IS were observed. CONCLUSIONS: These results suggest that the DOCK-ANGPTL3 SNPs and their haplotypes were associated with the angiographic severity to coronary artery atherosclerosis and the risk of CAD and IS in the Southern Chinese Han population.

Association of the HNF1A polymorphisms and serum lipid traits, the risk of coronary artery disease and ischemic stroke.

BACKGROUND: Hepatocyte nuclear factor-1α gene (HNF1A) single nucleotide polymorphisms (SNPs) have been associated with serum lipid traits in several previous genome-wide association studies. However, little is known about such associations in the Chinese populations. The present study aimed to determine the association of the HNF1A rs1169288, rs2259820, rs2464196 and rs2650000 SNPs and serum lipid traits, the risk of coronary artery disease (CAD) and ischemic stroke (IS). METHODS: The genotypes of the four SNPs in 562 CAD and 521 IS patients, as well as 594 healthy controls, were detected using the Snapshot technology. RESULTS: The genotype and allele distribution of the four SNPs was not different between controls and CAD or IS patients (p > 0.05 for all). rs1169288, rs2259820 and rs2464196 SNPs were significantly associated with serum lipid levels in both controls and CAD patients (p < 0.004-0.009). rs2259820 and rs2464196 SNPs were significantly associated with a lower risk of CAD [odds ratio (OR) = 0.64, 95% confidence interval (CI) = 0.44-0.91, p = 0.015 and OR =0.62, 95% CI = 0.43-0.89, p = 0.010, respectively]. Significant linkage disequilibrium was noted among the four SNPs (r2  > 0.5, D' > 0.8). The haplotype of rs1169288A-rs2259820C-rs2464196G-rs2650000A was associated with an increased risk of CAD (OR =1.95, 95% CI: 1.13-3.37, p = 0.015). Interactions of SNP-SNP (rs1169288-rs2464196-rs2650000) and haplotype-environment on the risk of CAD (A-C-G-A-smoking) or IS (A-C-G-A-sex and A-T-A-C-alcohol consumption) were also observed among these SNPs. CONCLUSIONS: These findings suggest that the HNF1A polymorphisms may be the genetic risk factors for CAD and IS.

Reactive oxygen species mediated T lymphocyte abnormalities in an iron-overloaded mouse model and iron-overloaded patients with myelodysplastic syndromes.

The adverse effects of iron overload have raised more concerns as a growing number of studies reported its association with immune disorders. This study aimed to investigate alterations in the immune system by iron overload in patients with myelodysplastic syndrome (MDS) and an iron-overloaded mouse model. The peripheral blood from patients was harvested to test the effect of iron overload on the subsets of T lymphocytes, and the level of reactive oxygen species (ROS) was also evaluated. The data showed that iron-overloaded patients had a lower percentage of CD3+ T cells and disrupted T cell subsets, concomitant with higher ROS level in lymphocytes. In order to explore the mechanism, male C57Bl/6 mice were intraperitoneally injected with iron dextran at a dose of 250 mg/kg every 3 days for 4 weeks to establish an iron-overloaded mouse model and the blood of each mouse was collected for the analysis of the T lymphocyte subsets and T cell apoptosis. The results showed that iron overload could reduce the percentage of CD3+ T cells and the ratio of Th1/Th2 and Tc1/Tc2 but increase the percentage of regulatory T (Treg) cells and the ratio of CD4/CD8. We also found that iron overload induced the apoptosis of T lymphocytes and increased its ROS level. Furthermore, these effects could be partially recovered after treating with antioxidant N-acetyl-L-cysteine (NAC) or iron chelator deferasirox (DFX). Taken together, these observations indicated that iron overload could selectively affect peripheral T lymphocytes and induce an impaired cellular immunity by increasing ROS level.

Association between single nucleotide polymorphism rs9534275 and the risk of coronary artery disease and ischemic stroke.

BACKGROUND: The present study was to detect the association of single nucleotide polymorphism (SNP) in the breast susceptibility gene 2 (BRCA2) and the risk of coronary artery disease (CAD) and ischemic stroke (IS). METHODS: Genotypes of the BRCA2 rs9534275 in 1822 unrelated subjects (CAD, 606; IS, 569; and healthy controls, 647) were determined by the polymerase chain reaction and restriction fragment length polymorphism and then confirmed by direct sequencing. RESULTS: The genotypic and allelic frequencies of rs9534275 were significantly different between the CAD, IS patients and controls (P = 0.033 and P = 0.027; respectively). The GG, GT/GG genotypes and G allele were associated with an increased risk of CAD and IS (CAD: P = 0.005 for GG vs. TT, P = 0.004 for GT/GG vs. TT, P = 0.005 for G vs. T; IS: P = 0.003 for GG vs. TT, P = 0.005 for GT/GG vs. TT; P = 0.002 for G vs. T). The GG, GT and GT/GG genotypes in the CAD, but not in healthy controls and IS patients, were associated with an increased serum total cholesterol (TC) and apolipoprotein B (ApoB) concentration. CONCLUSIONS: The present study shows that the G allele carriers of BRCA2 rs9534275 were associated with increased serum TC and ApoB levels in the CAD patients and increased risk of CAD and IS. TRIAL REGISTRATION: Retrospectively registered.

Clonal dissemination of KPC-2 producing Klebsiella pneumoniae ST11 clone with high prevalence of oqxAB and rmtB in a tertiary hospital in China: results from a 3-year period.

BACKGROUND: Carbapenemase-producing Klebsiella pneumoniae (CPKP) strains have emerged as a major problem for healthcare systems. The aim of this study was to determine the circulating clones and analyze the clinical and molecular characteristics of CPKP in our hospital. METHODS: A total of 74 carbapenemase producers collected from our hospital from 2012 to 2014 were analyzed for the prevalence of extended-spectrum ß-lactamase (ESBLs), plasmid-mediated quinolone resistance genes (PMQRs), exogenously acquired 16S rRNA methyltransferase (16S-RMTase), and plasmid-mediated AmpC enzyme (pAmpCs) by PCR and DNA sequencing. The sequence types (STs) of the carbapenemase producers were analyzed by multi-locus sequence typing (MLST). And Pulsed-field gel electrophoresis (PFGE) was performed to investigate the genetic relationship of KPC-2 producing strains. Clinical data were retrieved from the medical records. RESULTS: KPC-2 (n = 72) was the predominant enzyme followed by NDM-1 (n = 2); The genes blaCTX-M, blaSHV, blaTEM-1, blaDHA-1, rmtB, armA, oqxA, oqxB, and qnrB were present in 29 (39.2 %), 27 (36.5 %), 46 (62.2 %), 2 (2.7 %), 25 (33.8 %), 1 (1.4 %), 60 (81.1 %) and 56 (75.7 %), 6 (8.1 %) isolates, respectively. MLST analysis revealed 10 different STs. The most dominant ST was ST11 (78.4 %, 58/74), followed by ST15 (8.1 %, 6/74). PFGE patterns of the KPC-2 producing K. pneumoniae isolates exhibited clonal dissemination of ST11 and ST15 clones as well as a genetic diversity of the remaining strains. CONCLUSION: The intra- and inter-hospital cross-transmission of KPC-2-producing K. pneumoniae ST11 co-carrying oqxAB and rmtB in our hospital strongly suggested that rapid identification of colonized or infected patients and screening of carriers is quite necessary to prevent a scenario of endemicity.

Chromosome 9p21 and ABCA1 Genetic Variants and Their Interactions on Coronary Heart Disease and Ischemic Stroke in a Chinese Han Population.

The single nucleotide polymorphisms (SNPs) related to both coronary heart disease (CHD) and ischemic stroke (IS) in Chinese individuals have not been identified definitely. This study was developed to evaluate the genetic susceptibility to CHD and IS on the chromosome 9p21 and the adenosine triphosphate (ATP)-binding cassette transporter A1 genes (ABCA1) in a Chinese Han population. Genotypes of the rs1333040, rs1333042, rs4977574, rs2066715 and rs2740483 SNPs were determined in 1134 unrelated patients (CHD, 565 and IS, 569) and 541 controls. The frequencies of the rs4977574 genotypes and alleles between CHD and control groups, and the rs2740483 genotypes and alleles between IS and control groups were different (p = 0.006-0.001). The subjects with rs1333042GG genotype and the carriers of the rs4977574G allele were associated with increased risk of CHD. The carriers of the rs4977574G allele were associated with increased risk of IS. However, the carriers of the rs2740483C allele had lower risk of IS than the non-carriers of the rs2740483C allele after controlling for potential confounders. The rs4977574GG-age (>60 year) interaction increased the risk of CHD (p = 0.022), whereas the rs2740483CG/CC-body mass index (>24 kg/m²) interaction decreased the risk of IS (p = 0.035). The interactions of rs1333040-rs1333042 on the risk of CHD and IS were relatively strong, whereas the interactions of rs1333040-rs1333042-rs2066715 and rs1333040-rs1333042-rs2066715-rs2740483 on the risk of CHD, and rs1333040-rs1333042-rs4977574 and rs1333040-rs1333042-rs4977574-rs2740483 on the risk of IS were relatively weak. These findings suggest that some common variants on the chromosome 9p21 and ABCA1 and their interactions may significantly modify the risk of CHD and IS independent of effects on serum lipid levels.

Association of polymorphisms in the MAFB gene and the risk of coronary artery disease and ischemic stroke: a case-control study.

BACKGROUND: The v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog B gene (MAFB) has been associated with serum lipid levels in the Eurpean population, but little is known about such association in the Chinese population or in atherosclerosis-related patients. Therefore, the purpose of the present study was to assess the association of the single nucleotide polymorphisms (SNPs) in the MAFB and serum lipid levels and the risk of coronary artery disease (CAD) and ischemic stroke (IS) in the Chinese population. METHODS: A total of 1,065 unrelated patients (CAD, 525 and IS, 540) and 539 healthy controls were recruited in this study. Genotypes of the MAFB rs2902940 and rs6102059 SNPs were determined by the Snapshot technology platform. RESULTS: The rs2902940AA genotype was associated with an increased risk of CAD (adjusted OR = 1.63, 95% CI = 1.07-2.48, P = 0.023) and IS (adjusted OR = 1.69, 95% CI = 1.09-2.61, P = 0.017). The rs2902940GA/AA genotypes were also associated with an increased risk of CAD (adjusted OR = 1.56, 95% CI = 1.04-2.32, P = 0.030 for GA/AA vs. GG) and IS (adjusted OR = 1.72, 95% CI = 1.14-2.60, P = 0.010 for GA/AA vs. GG). Significant interactions were observed only in those with higher body mass index (BMI), hypertension and diabetes (P < 0.05). The subjects with rs2902940GA/AA genotypes in controls had lower serum ApoAI levels than the subjects with GG genotype (P = 0.024). CONCLUSIONS: The rs2902940A allele carriers in the MAFB conferred a decreased serum ApoAI level in controls and an increased risk of CAD and IS. The rs2902940GA/AA genotypes interacted with higher BMI, hypertension and diabetes to contribute the risk of CAD and IS.

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.

Molecular Characteristics of Salmonella Spp. Responsible for Bloodstream Infections in a Tertiary Hospital in Nanjing, China, 2019-2021.

Objective: To investigate the clinical and molecular characteristics of Salmonella spp. causing bloodstream infections (BSIs) in our hospital. Methods: We studied 22 clinical Salmonella isolates from BSIs and 16 from non-BSIs, performing antimicrobial susceptibility testing (AST) and whole genome sequencing (WGS). The analysis included serovars, antibiotic resistance genes (ARGs), virulence factors (VFs), sequence types (STs), plasmid replicons, and genetic relationships. We also assessed pathogenicity of the isolates causing BSIs through growth, biofilm formation, and anti-serum killing assays. Results: WGS analysis identified 13 Salmonella serovars, with four responsible for BSIs. S. Enteritidis was the most prevalent serovar, involved in 19 (50.0%) cases. BSIs were caused by 17S. Enteritidis, two S. Typhimurium, two S. Munster and one S. Diguel. Of the 38 isolates, 27 (71.1%) exhibited high resistance to ampicillin, and 24 (63.2%) to ampicillin/sulbactam. Thirty-six types of ARGs were identified, with blaTEM-1B (n = 25, 65.8%) being the most frequent. Ten plasmid replicons were found; the combination of IncFIB(S)-IncFII(S)-IncX1 was the most common in S. Enteritidis (94.7%). Fifteen STs were identified, among which ST11 was the most prevalent and clonally disseminated, primarily responsible for BSIs. A total of 333 different VFs were detected, 177 of which were common across all strains. No significant differences were observed between the BSI and non-BSI isolates in terms of resistance rates, ARGs, plasmid replicons, and VFs, except for seven VFs. No strong pathogenicity was observed in the BSI-causing isolates. Conclusion: BSIs were predominantly caused by clonally disseminated S. Enteritidis ST11, the majority of which carried multiple ARGs, VFs and plasmid replicons. This study provides the first data on clonally disseminated S. Enteritidis ST11 causing BSIs, highlighting the urgent need for enhanced infection control measures.

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 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.

EHBP1, TUBB, and WWOX SNPs, Gene-Gene and Gene-Environment Interactions on Coronary Artery Disease and Ischemic Stroke.

The associations among the EH domain-binding protein 1 (EHBP1), tubulin beta class I (TUBB), and WW domain-containing oxidoreductase (WWOX) single nucleotide polymorphisms (SNPs) and coronary artery disease (CAD) and ischemic stroke (IS) are not yet understood. This study aimed to detect the associations of these SNPs, gene-gene and gene-environment interactions and CAD and IS in the Guangxi Han population. A total of 1853 unrelated subjects were recruited into normal control (n = 638), CAD (n = 622), and IS (n = 593) groups. Related genotypes were determined by high-throughput sequencing. The genotypic and minor allelic frequencies of rs2278075 were different between the CAD and control groups, and those of rs2710642, rs3130685, and rs2278075 were also different between the IS and control groups. The rs2278075T allele, rs3130685-rs2222896-rs2278075, rs3130685-rs2222896-diabetes, rs3130685-rs2222896-drinking, and haplotype rs2710642A-rs10496099C-diabetes interactions were associated with increased risk, while G-T-G-C-G-A and G-T-T-T-G-T-drinking were associated with reduced risk of CAD. The rs2278075T and rs2710642G alleles, rs2710642G-rs10496099C haplotype, rs3130685-rs2278075-rs2222896, and rs2710642-rs2278075-hypertension interactions aggravated the association with IS, whereas the rs3130685T allele, rs2710642A-rs10496099C haplotype and the interactions of H1 (s2710642A-rs10496099C)-H2 (rs2710642G-rs10496099C)-drinking and I1 (A-C-G-C-A-A)-I3 (A-C-G-T-A-A)-I4 (A-C-G-T-G-A)-I5 (G-T-G-C-G-A) diminished the association with IS. Carrying WWOX rs2278075T was strongly associated with CAD or IS, while EHBP1 rs2710642 and TUBB rs3130685 might alter the association of IS by modifying the serum lipid profile. This study demonstrates that the EHBP1, TUBB, and WWOX SNPs, gene-gene and gene-environment interactions are associated with the risk of CAD and IS in the Guangxi Han population.

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.