[Research progress on chemical constituents from Kadsura genus and its pharmacological activities and clinical application].

The 29 plant species in the Kadsura genus of the Schisandraceae family are mainly distributed in eastern and southeas-tern Asia. Ten species of plants in this genus are distributed in China, some of which are folk medicinal plants with activating blood circulation, relieving pain, dispelling wind, and dehumidifying effects. Their main constituents are lignans and triterpenes. The current pharmacology and clinical studies have shown that their extracts and constituents have anti-rheumatoid arthritis, liver protection, antioxidation, anti-inflammatory, and other biological activities. The rheumatologic and liver diseases can also be treated with the plants in the clinic. The new chemical constituents reported in the last decade(2012 to date) from the plants of Kadsura genus in China, as well as their pharmacological effects and clinical applications in recent years were reviewed, so as to provide a theoretical basis for further research on the genus.

DGAT2-MOGAT2 SNPs and Gene-Environment Interactions on Serum Lipid Profiles and the Risk of Ischemic Stroke.

Background: The genetic susceptibility to ischemic stroke (IS) is still not well-understood. Recent genome-wide association studies (GWASes) found that several single nucleotide polymorphisms (SNPs) in the Diacylglycerol acyltransferase 2 gene (DGAT2) and monoacylglycerol O-acyltransferase 2 (MOGAT2) cluster were associated with serum lipid levels. However, the association between the DGAT2-MOGAT2 SNPs and serum lipid phenotypes has not yet been verified in the Chinese people. Therefore, the present study was to determine the DGAT2-MOGAT2 SNPs and gene-environment interactions on serum lipid profiles and the risk of IS. Methods: Genotyping of 5 SNPs (DGAT2 rs11236530, DGAT2 rs3060, MOGAT2 rs600626, MOGAT2 rs609379, and MOGAT2 rs10899104) in 544 IS patients and 561 healthy controls was performed by the next-generation sequencing technologies. The association between genotypes and serum lipid data was determined by analysis of covariance, and a corrected P-value was adopted after Bonferroni correction. Unconditional logistic regression analysis was performed to assess the association between genotypes and the risk of IS after adjustment of potential confounders. Results: The rs11236530A allele was associated with increased risk of IS (CA/AA vs. CC, OR = 1.45, 95%CI = 1.12-1.88, P = 0.0044), whereas the rs600626G-rs609379A-rs10899104G haplotype was associated with decreased risk of IS (adjusted OR = 0.67, 95% CI = 0.48-0.93, P = 0.018). The rs11236530A allele carriers had lower high-density lipoprotein cholesterol (HDL-C) concentrations than the rs11236530A allele non-carriers (P < 0.001). The interactions of rs11236530-smoking, rs3060-smoking and rs10899104-smoking influenced serum apolipoprotein B levels, whereas the interactions of rs11236530- and rs3060-alcohol affected serum HDL-C levels (P I < 0.004-0.001). The interaction of rs600626G-rs609379A-rs10899104G-alcohol (OR = 0.41, 95% CI = 0.22-0.76) and rs600626G-rs609379C-rs10899104T-alcohol (OR = 0.12, 95% CI = 0.04-0.36) decreased the risk of IS (P I < 0.0001). Conclusions: The rs11236530A allele was associated with decreased serum HDL-C levels in controls and increased risk of IS in patient group. The rs600626G-rs609379A-rs10899104G haplotype, the rs600626G-rs 609379A-rs10899104G-alcohol and rs600626G-rs609379C-rs10899104T-alcohol interactions were associated with decreased risk of IS. The rs11236530 SNP may be a genetic marker for IS in our study populations.

Effect of SYTL3-SLC22A3 Variants, Their Haplotypes, and G × E Interactions on Serum Lipid Levels and the Risk of Coronary Artery Disease and Ischaemic Stroke.

Background: The current study aimed to investigate the effects of synaptotagmin-like 3 (SYTL3) and solute carrier family 22 member 3 (SLC22A3) single nucleotide polymorphisms (SNPs) and gene-environment (G × E) interactions on blood lipid levels as well as the risk of coronary artery disease (CAD) and ischaemic stroke (IS) in the Southern Chinese Han population. Methods: The genetic makeup of 6 SYTL3-SLC22A3 SNPs in 2269 unrelated participants (controls, 755; CAD, 758 and IS, 756) of Chinese Han ethnicity was detected by the next-generation sequencing techniques. Results: The allele and genotype frequencies of the SYTL3 rs2129209 and SLC22A3 rs539298 SNPs were significantly different between the case and control groups. The SLC22A3 rs539298 SNP was correlated with total cholesterol (TC) levels in controls, the rs539298G allele carriers maintained lower TC levels than the rs539298G allele non-carriers. At the same time, the SLC22A3 rs539298 SNP interacted with alcohol consumption reduced the risk of CAD and IS. The SYTL3-SLC22A3 A-C-A-A-A-A, G-T-C-G-C-A and A-T-A-A-C-A haplotypes increased and the A-C-A-A-C-G haplotype reduced the risk of CAD, whereas the SYTL3-SLC22A3 A-C-A-A-A-A, G-T-C-G-A-G and A-T-A-A-C-A haplotypes increased and the A-C-A-A-A-G and A-C-A-A-C-G haplotypes reduced the risk of IS. In addition, several SNPs interacted with alcohol consumption, body mass index ≥ 24 kg/m2 and cigarette smoking to affect serum lipid parameters such as triglyceride, high-density lipoprotein cholesterol, TC, and apolipoprotein A1 levels. Conclusions: Several SYTL3-SLC22A3 variants, especially the rs539298 SNP, several haplotypes, and G × E interactions, were related to blood lipid parameters and the risk of CAD and IS in the Southern Chinese Han population.

XKR6 rs7014968 SNP Increases Serum Total Cholesterol Levels and the Risk of Coronary Heart Disease and Ischemic Stroke.

The X Kell blood group complex subunit-related family member 6 (XKR6) gene single-nucleotide polymorphisms (SNPs) have been associated with serum lipid profiles and the risk of coronary heart disease (CHD) and ischemic stroke (IS) in several previous studies, but the association between the XKR6 rs7014968 SNP and serum lipid levels and the risk of CHD and IS has not been detected previously. This study aims to explore the association between the XKR6 rs7014968 SNP and serum lipid traits and the susceptibility to CHD and IS in the Guangxi Han Chinese population. Snapshot technology was used to determine the genotypes of the XKR6 rs7014968 SNP in 624 controls, 588 patients with CHD, and 544 patients with IS. The XKR6 rs7014968C allele carriers in the control group had higher serum total cholesterol (TC) levels than the C allele noncarriers (P = .025). The XKR6 rs7014968C allele carriers also had an increased risk of CHD and IS (P < .05-.01). Stratified analysis showed that the patients with the rs7014968C allele in the female, age >60 years, body mass index (BMI) >24 kg/m2, and hypertension subgroups had a higher risk of CHD than those in the subgroup counterparts. The patients with the rs7014968C allele in the male, BMI > 24 kg/m2, smoker, and hypertension subgroups also had a higher risk of IS than those in the subgroup counterparts. These results suggest that the XKR6 rs7014968 SNP is likely to increase the risk of CHD and IS by increasing serum TC levels in our study populations.

A novel lncRNA-miRNA-mRNA triple network identifies lncRNA TWF1 as an important regulator of miRNA and gene expression in coronary artery disease.

BACKGROUND: Long non-coding RNAs (lncRNAs) are involved in numerous physiological functions. Yet, their mechanisms in coronary artery disease (CAD) are not well understood. METHODS: The expression profile of genes associated to CAD was reannotated into the lncRNA-mRNA biphasic profile. The target microRNA data were used to design a global CAD triple network. Thereafter, we conducted a functional enrichment analysis and clustering using the triple network from the level of topology analyses. The expression of four non-coding RNAs (ncRNAs) was measured by qRT-PCR and the risk of CAD was calculated by nomogram. The prognostic value of three ncRNAs was evaluated using receiver operating characteristic (ROC) curve. RESULTS: A CAD lncRNA-miRNA-mRNA network was constructed which included 15 mRNAs, 3 miRNAs, 19 edges and one lncRNA. Nomogram showed that four ncRNAs were the risk of CAD. After RT-PCR validation in four ncRNAs between CAD and non-CAD samples, only three ncRNAs had significant meaning for further analysis. ROC curve showed that TWF1 presented an area under curve (AUC) of 0.862, the AUC of hsa -miR-142-3p was 0.856 and hsa -miR126-5p was 0.822. After the pairwise comparison, we found that TWF1 had significant statistical significance (P TWF1-142 < 0.05 and P TWF1-126 < 0.01). The results of functional enrichment analysis of interacting gene and microRNA showed that the shared lncRNA TWF1 may be a new factor for CAD. CONCLUSIONS: This investigation on the regulatory networks of lncRNA-miRNA-mRNA in CAD suggests that a novel lncRNA, lncRNA TWF1 is a risk factor for CAD, and expands our understanding into the mechanisms involved in the pathogenesis of CAD.

Integrated analysis of gene expression changes associated with coronary artery disease.

BACKGROUND: This study investigated the pathways and genes involved in coronary artery disease (CAD) and the associated mechanisms. METHODS: Two array data sets of GSE19339 and GSE56885 were downloaded. The limma package was used to analyze the differentially expressed genes (DEGs) in normal and CAD specimens. Examination of DEGs through Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and Gene Ontology annotation was achieved by Database for Annotation, Visualization and Integrated Discovery (DAVID). The Cytoscape software facilitated the establishment of the protein-protein interaction (PPI) network and Molecular Complex Detection (MCODE) was performed for the significant modules. RESULTS: We identified 413 DEGs (291 up-regulated and 122 down-regulated). Approximately 256 biological processes, only 1 cellular component, and 21 molecular functions were identified by GO analysis and 10 pathways were enriched by KEGG. Moreover, 264 protein pairs and 64 nodes were visualized by the PPI network. After the MCODE analysis, the top 4 high degree genes, including interleukin 1 beta (IL1B, degree = 29), intercellular adhesion molecule 1 (ICAM1, degree = 25), Jun proto-oncogene (JUN, degree = 23) and C-C motif chemokine ligand 2 (CCL2, degree = 20) had been identified to validate in RT-PCR and Cox proportional hazards regression between CAD and normals. CONCLUSIONS: The relative expression of IL1B, ICAM1 and CCL2 was higher in CAD than in normal controls (P < 0.05-0.001), but only IL1B and CCL2 genes were confirmed after testing the gene expression in blood and/or analyzing in Cox proportional hazards regression (P < 0.05-0.001), and the proper mechanism may involve in the AGE-RAGE signaling pathway, fluid shear stress, the tumor necrosis factor (TNF) and cytokine-cytokine receptor interaction.

Integrated DNA methylation and gene expression analysis in the pathogenesis of coronary artery disease.

To evaluate DNA methylation sites and gene expression associated with coronary artery disease (CAD) and the possible pathological mechanism involved, we performed (1) genome-wide DNA methylation and mRNA expression profiling in peripheral blood datasets from the Gene Expression Omnibus repository of CAD samples and controls; (2) functional enrichment analysis and differential methylation gene regulatory network construction; (3) validation tests of 11 differential methylation positions of interest and the corresponding gene expression; and (4) correlation analysis for DNA methylation and mRNA expression data. A total of 669 differentially expressed mRNAs were matched to differentially methylated genes. After disease ontology, Kyoto Encyclopedia of Genes and Genomes pathway, gene ontology, protein-protein interaction and network construction and module analyses, 11 differentially methylated positions (DMPs) corresponding to 11 unique genes were observed: BDNF - cg26949694, BTRC - cg24381155, CDH5 - cg02223351, CXCL12 - cg11267527, EGFR - cg27637738, IL-6 - cg13104385, ITGB1 - cg20545410, PDGFRB - cg25613180, PIK3R1- cg00559992, PLCB1 - cg27178677 and PTPRC - cg09247619. After validation tests of 11 DMPs of interest and the corresponding gene expression, we found that CXCL12 was less hypomethylated in the CAD group, whereas the relative expression of ITGB1, PDGFRB and PIK3R1 was lower in CAD samples, and CXCL12 and ITGB1 methylation was negatively correlated with their expression. This study identified the correlation between DNA methylation and gene expression and highlighted the importance of CXCL12 in CAD pathogenesis.

TRIB1 and TRPS1 variants, G × G and G × E interactions on serum lipid levels, the risk of coronary heart disease and ischemic stroke.

This study aimed to assess the association of the tribbles pseudokinase 1 (TRIB1) and transcriptional repressor GATA binding 1 (TRPS1) single nucleotide polymorphisms (SNPs) and the gene-gene (G × G) and gene-environment (G × E) interactions with serum lipid levels, the risk of coronary heart disease (CHD) and ischemic stroke (IS) in the Guangxi Han population. Genotyping of the rs2954029, rs2980880, rs10808546, rs231150, rs2737229 and rs10505248 SNPs was performed in 625 controls and 1146 unrelated patients (CHD, 593 and IS, 553). The genotypic and allelic frequencies of some SNPs were different between controls and patients (CHD, rs2954029 and rs231150; IS, rs2954029 and rs2980880; P < 0.05-0.01). Two SNPs were associated with increased risk of CHD (rs2954029 and rs231150) and IS (rs2954029) in different genetic models. Several SNPs in controls were associated with total cholesterol (rs2954029, rs2980880 and rs2737229), triglyceride (rs2954029 and rs10808546), low-density lipoprotein cholesterol (rs2954029), high-density lipoprotein cholesterol (rs2980880 and rs231150) and apolipoprotein A1 (rs2737229) levels. The rs2954029TA/AA-age (>60 year) interaction increased the risk of CHD, whereas the rs10808546CT/TT-drinking interaction decreased the risk of IS. The rs2954029A-rs2980880C-rs10808546C haplotype was associated with increased risk of CHD and IS. The rs2954029A-rs2980880T-rs10808546C haplotype was associated with increased risk of CHD. The rs2954029-rs231150 interactions had an increased risk of both CHD and IS. These results suggest that several TRIB1 and TRPS1 SNPs were associated with dyslipidemia and increased risk of CHD and IS in our study population. The G × G and G × E interactions on serum lipid levels, and the risk of CHD and IS were also observed.

ANGPTL4 variants and their haplotypes are associated with serum lipid levels, the risk of coronary artery disease and ischemic stroke and atorvastatin cholesterol-lowering responses.

BACKGROUND: This study aimed to assess the association between the angiopoietin-like protein 4 gene (ANGPTL4) single nucleotide polymorphisms (SNPs) and serum lipid levels, the risk of coronary artery disease (CAD) and ischemic stroke (IS), and response to atorvastatin therapy in a Southern Chinese Han population. METHODS: Genotypes of the ANGPTL4 rs4076317, rs7255436, rs1044250 and rs2967605 SNPs in 1,654 unrelated subjects (CAD, 568; IS, 537; and controls, 549) were determined by the Snapshot technology. Another group of 724 hyperlipidemic patients was selected and treated with atorvastatin calcium tablet 20 mg/day for 8 weeks. RESULTS: The rs2967605 CT/TT genotypes were associated with a decreased risk of CAD (adjusted OR = 0.68, 95% CI = 0.47-0.99, P = 0.043 for CT/TT vs. CC) and IS (adjusted OR = 0.55, 95% CI = 0.38-0.80, P = 0.020 for CT/TT vs. CC). There was no significant association between the four SNPs and angiographic severity of CAD. The subjects with the rs4076317 CG/CC genotypes in controls had higher total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels than the subjects with the GG genotype (P < 0.001; a P < 0.0018 was regarded statistically significant by the Bonferroni correction). The subjects with rs4076317CG/GG genotypes had lower TC and LDL-C levels than the subjects with CC genotype after atorvastatin treatment (P < 0.001). CONCLUSIONS: The observed associations suggest that the ANGPTL4 variants have a potential role on serum lipid levels and atherosclerosis-related diseases in the Chinese Han population, especially the ANGPTL4 rs4076317 and rs2967605 SNPs.

Association between the PPP1R3B polymorphisms and serum lipid traits, the risk of coronary artery disease and ischemic stroke in a southern Chinese Han population.

BACKGROUND: Little is known about the association of the protein phosphatase 1 regulatory subunit 3B gene (PPP1R3B) single nucleotide polymorphisms (SNPs) and serum lipid levels, the risk of coronary artery disease (CAD) and ischemic stroke (IS) in the Chinese populations. This study detected such association in a Southern Chinese Han population. METHODS: Genotypes of 4 novel PPP1R3B SNPs (rs12785, rs330910, rs330915 and rs9949) in 1704 Han Chinese (CAD, 556; IS, 531 and control, 617) were determined by the Snapshot technology. RESULTS: The rs12785A and rs9949A allele frequency was higher in both CAD/IS patients than in controls. The rs330910T and rs330915T allele frequency was also higher in CAD patients than in controls. The rs330910T allele carriers in controls had lower serum low-density lipoprotein cholesterol (LDL-C) levels than the rs330910T allele non-carriers (P < 0.0014). The rs12785A, rs9949A and rs330910T allele carriers were associated with an increased risk of CAD (P = 0.008-0.004). There was strong linkage disequilibrium among the 4 SNPs in the controls and CAD/IS patients. The T-A-A-G haplotype was associated with a decreased risk of CAD and IS, whereas the A-A-T-A haplotype was associated with an increased risk for IS. Haplotype-environment interactions on the risk of CAD and IS were also observed. CONCLUSIONS: Several PPP1R3B polymorphisms were associated with serum LDL-C levels, the risk of CAD and IS in the Southern Chinese Han population. But these findings still need to be confirmed in the other populations with larger sample sizes.

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.

Erratum: The association between the DNAH11 rs10248618 SNP and serum lipid traits, the risk of coronary artery disease, and ischemic stroke.

[This corrects the article on p. 4585 in vol. 11, PMID: 31949857.].

TTC39B rs1407977 SNP is associated with the risk of coronary heart disease and ischemic stroke.

Previous genome-wide association studies have showed that several tetratricopeptide repeat domain protein 39B gene (TTC39B) single nucleotide polymorphisms (rs581080 and rs471364) were associated with serum high-density lipoprotein cholesterol levels among populations of European ancestry, but the results are inconsistent. Furthermore, little is known about the association between TTC39B SNPs and the susceptibility to coronary heart disease (CHD) and ischemic stroke (IS). Therefore, this study was undertaken to detect the association between the TTC39B rs1407977 SNP and serum lipid levels and the risk of CHD and IS in a Southern Chinese Han population. Genotyping of the SNP in 1741 unrelated subjects (healthy controls, 624; CHD patients, 578 and IS patients, 539) was performed by the Snapshot Technology. The genotypic and allelic frequencies of the SNP were different between the control subjects and CHD patients, or between the control subjects and IS patients (P ≤ 0.001). The T allele frequency was higher in CHD (16.2%) and IS (15.0%) patients than in controls (9.8%). The T allele carriers had higher risk of CHD (OR = 1.728, 95% CI = 1.290-2.316, P < 0.001) and IS (OR = 1.518, 95% CI = 1.182-2.116, P = 0.002) than the T allele non-carriers after controlling for potential confounders. No significant association was observed between the TTC39B rs1407977 SNP and all seven serum lipid traits. These results suggest that the TTC39B rs1407977 SNP is associated with the risk of CHD and IS in our study population and does not depend on serum lipid levels.

Association between the MGAT1 rs634501 polymorphism and serum lipid traits in the Chinese Han and Maonan ethnic groups.

Little is known about the association of monoacylglycerol acyltransferase 1 gene (MGAT1) rs634501 single nucleotide polymorphism (SNP) and serum lipid profiles in the Chinese populations. The aim of this study was to detect the association of the MGAT1 rs634501 SNP and several environmental factors with serum lipid levels in the Chinese Maonan and Han populations. Genotypes of the SNP in 2014 unrelated participants (Han, 986; Maonan, 1028) were determined by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and confirmed by direct sequencing. The genotypic and allelic frequencies of the MGAT1 rs634501 SNP were significantly different between the Han and Maonan populations as well as between males and females in the Maonan population. The A allele carriers had lower serum apolipoprotein (Apo) A1 levels, the ApoA1/ApoB ratio and higher ApoB levels in Maonans; and lower high-density lipoprotein cholesterol, ApoA1 levels, ApoA1/ApoB ratio, and higher triglyceride levels in Han than the A allele non-carriers. There were also different associations of the MGAT1 rs634501 SNP and serum lipid profiles between males and females in the both ethnic groups. Serum lipid parameters in the two ethnic groups were also associated with several environmental factors. These results suggest that the association of the MGAT1 rs634501 SNP and serum lipid parameters might have ethnic- and/or sex-specificity.

The association between the DNAH11 rs10248618 SNP and serum lipid traits, the risk of coronary artery disease, and ischemic stroke.

Previous genome-wide association studies have shown that the rs10248618 single nucleotide polymorphism (SNP) in the dynein axonemal heavy chain 11 gene (DNAH11) has been associated with serum high-density lipoprotein cholesterol (HDL-C) levels. However, little is known about such association in the Chinese population. The present study was performed to clarify the association between the DNAH11 rs10248618 SNP and serum lipid traits and the risk of coronary artery disease (CAD) and ischemic stroke (IS) in the Guangxi Han population. Genotypes of the DNAH11 rs10248618 SNP in 1,213 unrelated patients (CAD, 600 and IS, 613) and 631 healthy controls were determined by snapshot technology. The genotypic and allelic frequencies of the SNP were significantly different between the CAD/IS patients and the controls (P < 0.01 for all). The CT/TT genotypes and the T allele were associated with an increased risk of CAD and IS (CAD: P < 0.01 for CT/TT vs. CC and T vs. C; IS: P < 0.01 for CT/TT vs. CC and T vs. C). The CT/TT genotypes in the healthy controls, but not in CAD or IS patients, were associated with a decreased serum HDL-C and apolipoprotein (Apo) A1 concentration. These results suggest that the DNAH11 rs10248618 SNP is associated with the risk of CAD and IS in our study population. It is likely to increase the risk of CAD and IS by reducing serum HDL-C and ApoA1 levels.

Association between the TIMD4-HAVCR1 variants and serum lipid levels, coronary heart disease and ischemic stroke risk and atorvastatin lipid-lowering efficacy.

Little is known about the association of the TIMD4 (T-cell immunoglobulin and mucin domain 4 gene)-HAVCR1 (hepatitis A virus cellular receptor 1) variants and lipid metabolism, the risk of coronary heart disease (CHD) and ischemic stroke (IS). The present study aimed to determine the TIMD4-HAVCR1 variants, their haplotypes and gene-environment interactions on serum lipid levels, the risk of CHD and IS, and the lipid-lowering efficacy of atorvastatin in a southern Chinese Han population. Genotypes of three variants in 622 controls, 579 CHD, and 546 IS patients were determined by the Snapshot technology. Atorvastatin calcium tablet (20 mg/day) was given in 724 hyperlipidemic patients for 8 weeks after genotyping. The rs12522248 genotypic and allelic frequencies were different between controls and patients, and were associated with the risk of CHD and IS. The rs1501908G-rs12522248T-rs2036402T haplotype was associated with an increased risk of CHD; the G-C-T haplotype was associated with lower risk of CHD; and the C-C-C haplotype was associated with an increased risk of IS. Variants and their haplotypes in controls were associated with triglyceride (rs1501908), low-density lipoprotein cholesterol (LDL-C, rs1501908, G-T-T), high-density lipoprotein cholesterol (HDL-C, rs12522248, C-C-C) and the ratio of total cholesterol (TC) to HDL-C (C-C-C). Interactions of rs1501908- and rs2036402-alcohol (HDL-C); rs1501908- and rs12522248-high body mass index (hBMI, ≥24 kg/m2; TC); and TIMD4-HAVCR1 variants-atorvastatin on several lipid parameters were detected. Interactions of rs12522248TC/CC-hBMI, G-T-T-, and C-C-C-smoking on the risk of CHD; and C-C-C-smoking, C-C-C-, and G-C-T-hBMI on the risk of IS were also observed. These findings suggest that the TIMD4-HAVCR1 variants may be the genetic risk factors for CHD and IS.

The effect of MVK-MMAB variants, their haplotypes and G×E interactions on serum lipid levels and the risk of coronary heart disease and ischemic stroke.

AIM: This study aimed to detect the association of the mevalonate kinase (MVK) and methylmalonic aciduria (cobalamin deficiency) cblB type (MMAB) gene variants, their haplotypes, and gene-environment (G×E) interactions on serum lipid levels and the risk of coronary heart disease (CHD) and ischemic stroke (IS) in a Chinese Han population. METHODS: Genotyping of the rs3759387, rs7134594, rs877710 and rs9593 SNPs in 846 CHD and 869 IS patients and 847 healthy controls was performed by PCR-RFLP and Sanger sequencing. Logistic regression and factor regression were used to investigate the association of 4 MVK-MMAB SNPs and serum lipid levels and the risk of CHD and IS. RESULTS: The genotypic and allelic frequencies of the rs3759387 and rs7134594 SNPs differed between controls and patients (P < 0.0125-0.001). The rs3759387 SNP was associated with the risk of CHD and IS in different genetic models. The A-T-G-A and C-T-C-T haplotypes were associated with increased risk of CHD. The haplotype of A-T-G-A was associated with an increased risk of IS, whereas the C-T-G-A haplotype was associated with a decreased risk of IS. Interactions of C-T-C-T-smoking or C-T-C-T-age on the risk of CHD, and A-T-G-A-hypertension or A-T-G-A-age on the risk of IS were also observed. The subjects with the rs3759387AA genotype in controls had lower high-density lipoprotein cholesterol (HDL-C) levels than did the subjects with AC/CC genotypes. Several SNPs interacted with alcohol consumption and cigarette smoking to increase serum HDL-C and apolipoprotein A1 levels, but they interacted with body mass index ≥ 24 kg/m2 to decrease serum HDL-C and apolipoprotein A1 levels. CONCLUSION: Several MVK-MMAB variants, especially the rs3759387 SNP, 4 main haplotypes, and G×E interactions were associated with serum lipid levels and the risk of CHD and IS in a Chinese Han population.

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.

DNAH11 rs12670798 variant and G × E interactions on serum lipid levels, coronary heart disease, ischemic stroke and the lipid-lowering efficacy of atorvastatin.

Previous genome-wide association studies have showed that the rs12670798 variant in the dynein axonemal heavy chain 11 gene (DNAH11) is associated with some serum lipid phenotypes. The present study was undertaken to detect the DNAH11 rs12670798 variant and G × E interactions on serum lipid levels, coronary heart disease (CHD), ischemic stroke (IS), and the lipid-lowering efficacy of atorvastatin in the Chinese Han population. This study included 1,108 unrelated patients (CHD, 568 and IS, 540) and 541 healthy controls. Genotypes of the DNAH11 rs12670798 were determined by the Snapshot technology. A total of 724 hyperlipidemic patients were treated with atorvastatin calcium tablet 20 mg per day for 8 weeks after genotyping. Serum total cholesterol (TC) levels in controls were different among the three genotypes of the rs12670798 (P = 0.019), the C allele carriers had higher TC levels than the C allele non-carriers. The C allele carriers were associated with an increased risk of CHD (CT genotype: OR = 1.345, 95% CI = 0.975-1.855, P = 0.071; CC genotype: OR = 1.590, 95% CI = 1.109-2.278, P = 0.012). The C allele carriers were also associated with an increased risk of IS (CT genotype: OR = 1.597, 95% CI = 1.153-2.213, P = 0.005; CC genotype: OR = 1.722, 95% CI = 1.192-2.488, P = 0.004). The C allele carriers had lower TC, low-density lipoprotein cholesterol, apolipoprotein (Apo) A1 and ApoB levels than the C allele non-carriers after atorvastatin treatment. Stratified analysis showed that the DNAH11 rs12670798 may interact with the gender, age, body mass index, cigarette smoking, and alcohol consumption to affect the risk of CHD and IS. The DNAH11 rs12670798 variant was associated with elevated serum TC levels, and increased risk of CHD and IS in the Chinese Han population. The C allele carriers had higher serum TC levels and the risk of CHD and IS than the C allele non-carriers, but they had lower TC, LDL-C, ApoA1 and ApoB levels than the C allele non-carriers after atorvastatin treatment.