Association between rs10118757(A/G) in methylthioadenosine phosphorylase gene and coronary artery disease in Chinese Hans

Studies focusing on the association of gene methylthioadenosine phosphorylase (MTAP) with the risk of coronary artery disease (CAD) and myocardial infarction (MI) are limited.     

Association between interleukin-6 gene − 174 G/C polymorphism and the risk of coronary heart disease: A meta-analysis of 20 studies including 9619 cases and 10,919 controls

Interleukin-6 (IL-6) gene − 174 G/C polymorphism has been reported to be associated with coronary heart disease (CHD), but the results remain inconclusive. The present meta-analysis was therefore designed to clarify these controversies. This meta-analysis was performed by searching PubMed, Embase and Web of Science databases. A total of 20 studies including 9619 CHD cases and 10,919 controls were combined showing no evidence of association between IL-6 gene − 174 G/C polymorphism and CHD risk (for C/C + C/G vs. G/G: OR = 1.10, 95% CI = 0.99–1.22, p = 0.07; for C/C vs. C/G + G/G: OR = 1.08, 95% CI = 0.93–1.24, p = 0.33; for C/C vs. G/G: OR = 1.16, 95% CI = 0.97–1.39, p = 0.11; for C allele vs. G allele: OR = 1.10, 95% CI = 1.00–1.21, p = 0.06). Moreover, we also did not find significant association between IL-6 gene − 174 G/C polymorphism and myocardial infarction (MI) risk. However, in the subgroup analysis by ethnicity, significant association was found among Asians (for C/C + C/G vs. G/G: OR = 1.35, 95% CI = 1.05–1.63, p = 0.02). In summary, the present meta-analysis suggests that IL-6 gene − 174 G/C polymorphism is associated with increased CHD risk among Asians. However, due to the small subjects included in the subgroup analysis of Asians, the results should be interpreted with caution.     

Association of heat shock protein70-2 (HSP70-2) gene polymorphism with coronary artery disease in an Iranian population

Background

Coronary artery disease (CAD) is an inflammatory process and a major cause of mortality and morbidity. The (heat shock protein70-2) HSP70-2 gene is reported to be associated with coronary artery disease possibly by affecting the regulation of pro-inflammatory cytokines such as TNF-α. The association between CAD and the HSP70-2 gene + 1267A>G polymorphism has been studied in some populations but there are no data about this association in the Iranian population.

Aim

We have investigated the association between the HSP70-2 gene + 1267A>G polymorphism and angiographically defined CAD within an Iranian population.

Methods

We determined the presence of the HSP70-2 gene + 1267A>G polymorphism in 628 patients with CAD and 307 healthy individuals using PCR-RFLP. Of the patients, 433 (68%) had > 50% stenosis (CAD +) and the remaining 195 patients had < 50% stenosis (CAD −), based on coronary angiography. Angiogram positive patients were subdivided into three groups: those with single (n = 113), double (n = 134), and triple vessels (n = 186) disease.

Results

A significant higher frequency of AG + GG genotypes (G allele carriers) was observed in angiogram positive and angiogram negative groups compared to controls in a dominant analysis model of the HSP70-2 gene + 1267A>G position (51.2 vs. 43.2, P = 0.002, OR = 1.37) (51.0 vs. 43.2, P = 0.01, OR = 1.37). The allele frequency of the HSP70-2 G was also significantly higher in angiogram positive and angiogram negative groups compared to the control group (51.2 vs. 43.2, P = 0.002, OR = 1.37) (51.0 vs. 43.2, P = 0.01, OR = 1.37).

Conclusion

These results suggest that HSP70-2 + 1267 polymorphism may influence the risk of CAD in Iranian population, however further studies are needed to clarify the role of other HSP70-2 gene polymorphisms in the pathogenesis of the CAD.     

Association of TLR and TREM-1 gene polymorphisms with risk of coronary artery disease in a Russian population

Atherosclerosis, manifesting itself as acute coronary syndrome, stroke, and peripheral arterial diseases, is a chronic progressive inflammatory disease which is driven by responses of both innate and adaptive immunity. Toll-like receptors (TLRs) and Triggering Receptor Expressed on Myeloid Cells-1 (TREM-1) are important effectors of the innate immune system, and polymorphisms within genes encoding them may increase risk of occurrence of various pathologies including cardiovascular disorders. Thus, we carried out a genetic association study on the sample of 702 consecutive Caucasian (Russian) patients with coronary artery disease (CAD) and 300 age-, sex-, and ethnicity-matched healthy controls. We revealed that the C/C genotype of the TLR1 rs5743551 polymorphism was significantly associated with a reduced risk of CAD according to the recessive model (OR = 0.41, 95% CI = 0.20–0.84, P = 0.017, adjusted by age and gender). Concerning TREM-1 gene polymorphisms, we found that A/A genotype of the rs2234237 polymorphism, the G/G genotype of the rs6910730 polymorphism, the C/C genotype of the rs9471535 polymorphism, and the T/T genotype of the rs4711668 polymorphism were significantly associated with elevated CAD risk according to the recessive model (OR = 5.52, 95% CI = 1.17–25.98, P = 0.011; OR = 4.28, 95% CI = 1.09–16.81, P = 0.021; OR = 5.55, 95% CI = 1.18–26.09, P = 0.011, and OR = 1.66, 95% CI = 1.10–2.52, P = 0.014, respectively, adjusted by age and gender). Conversely, the G allele of the rs1817537 polymorphism, the T allele of the rs2234246 polymorphism, and the T allele of the rs3804277 polymorphism significantly correlated with similarly decreased risk of CAD according to the dominant model (OR = 0.57, 95% CI = 0.40–0.81, P = 0.0013; OR = 0.59, 95% CI = 0.42–0.84, P = 0.003, and OR = 0.58, 95% CI = 0.41–0.81, P = 0.0014, respectively, adjusted by age and gender). We conclude that certain TLR and TREM-1 gene polymorphisms may be associated with CAD in Russian population; however, their significance as predictive and pathogenic markers of CAD should be interpreted with caution in other populations.     

Haplotype study of the CYP4A11 gene and coronary artery disease in Han and Uygur populations in China

Background

CYP4A11 converts arachidonic acid to 20-hydroxyeicosatetraenoic acid (20-HETE), which has a crucial role in the modulation of cardiovascular homeostasis. We assessed the association between the human CYP4A11 gene and coronary artery disease (CAD) in Han and Uygur populations in China.

Methods and Results

In the Han population, 361 CAD patients and 315 controls were genotyped for four single-nucleotide polymorphisms (SNPs) of the human CYP4A11 gene (rs9332978, rs4660980, rs3890011, rs1126742). In the Uygur population, 331 CAD patients and 182 controls were genotyped for the same four SNPs. Data were assessed via haplotype-based case–control studies. For the Han population, the significance of the recessive model of SNP3 (GG vs. CC+GC) between CAD patients and control subjects was retained after adjustment for EH, DM and smoking (for men, 95% CI: 1.173–3.013, P = 0.009). The G-G-T haplotype in CAD was significantly higher than that in the control group (P = 0.037). In the Uygur population, neither the distribution of genotypes and alleles for the four SNPs nor the distribution of haplotypes constructed with the same three SNPs showed a significant difference between CAD and control subjects.

Conclusions

The GG genotype of rs3890011 and the G-G-T haplotype in the CYP4A11 gene could be a useful genetic marker of CAD in Han populations in China.     

Uncoupling protein 2 − 866G/A and uncoupling protein 3 − 55C/T polymorphisms in young South African Indian coronary artery disease patients

Background

Uncoupling proteins (UCPs) 2 and 3 play an important role in the regulation of oxidative stress which contributes to chronic inflammation. Promoter polymorphisms of these genes have been linked to chronic diseases including heart disease and type II diabetes mellitus in several populations. This is the first investigation of the UCP2 − 866G/A rs659366 and UCP3 − 55C/T rs1800849 polymorphisms in young South African (SA) Indians with coronary artery disease (CAD).

Methods

A total of 300 subjects were recruited into this study of which 100 were SA Indian males with CAD, 100 age- (range 24–45 years), gender- and race-matched controls and 100 age-matched black SA males. The frequency of the UCP2 − 866G/A and UPC3 − 55C/T genotypes was assessed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP).

Results

The heterozygous UCP2 − 866G/A and homozygous UCP3 − 55C/C genotypes occurred at highest frequency in CAD patients (60% and 64%, respectively) compared to SA Indian controls (52% and 63%) and SA Black controls (50% and 58%). The UCP2 − 886G/A (OR = 1.110; 95% CI = 0.7438–1.655; p = 0.6835) and UCP3 − 55C/T (OR = 0.788; 95% CI = 0.482–1.289; p = 0.382) polymorphisms did not influence the risk of CAD.The rare homozygous UCP3 − 55T/T genotype was associated with highest fasting glucose (11.87 ± 3.7 mmol/L vs. C/C:6.11 ± 0.27 mmol/L and C/T:6.48 ± 0.57 mmol/L, p = 0.0025), HbA1c (10.05 ± 2.57% vs. C/C:6.44 ± 0.21% and C/T:6.76 ± 0.35%, p = 0.0006) and triglycerides (6.47 ± 1.7 mmol/L vs. C/C:2.33 ± 0.17 mmol/L and C/T:2.06 ± 0.25 mmol/L, p < 0.0001) in CAD patients.

Conclusion

The frequency of the UCP2 − 866G/A and UCP3 − 55C/T polymorphisms was similar in our SA Indian and SA Black groups. The presence of the UCP2 − 866G/A and UCP3 − 55C/T polymorphisms does not influence the risk of CAD in young South African Indian CAD patients.