SELP genetic polymorphisms may contribute to the pathogenesis of coronary heart disease and myocardial infarction: a meta-analysis

We conducted a meta-analysis of case–control studies to determine whether SELP genetic polymorphisms contribute to the pathogenesis of coronary heart disease (CHD) and myocardial infarction (MI). A range of electronic databases were searched: MEDLINE (1966–2013), the Cochrane Library Database (Issue 12, 2013), EMBASE (1980–2013), CINAHL (1982–2013), Web of Science (1945–2013) and the Chinese biomedical database (1982–2013) without language restrictions. Meta-analysis was performed with the use of the STATA statistical software. Nine case–control studies with a total of 3,154 CHD patients, 1,608 MI patients and 17,304 healthy controls were involved in this meta-analysis. Six common polymorphisms in the SELE gene were assessed, including ?1969G/A (rs1800805 G > A), ?1817T/C (rs1800808 T > C), ?2123C/G (rs1800807 C > G), Thr715Pro (rs6136 A > C), Leu599Val (rs6133 G > T), and Ser290Asn (rs6131 C > T). Our findings illustrated significantly positive associations of SELE genetic polymorphisms with the development of CHD and MI. The results of subgroup analysis by SNP type indicated that ?1969G/A, ?1817T/C, ?2123C/G, Thr715Pro and Ser290Asn in the SELP gene might be strongly correlated with CHD and MI risk, but no similar results were found in SELP Leu599Val polymorphism. In the subgroup analysis by ethnicity, our results indicated significant relationships between SELE genetic polymorphisms and the pathogenesis of CHD and MI among Asians and Caucasians. However, we observed no significant associations between SELP genetic polymorphisms and the risk of CHD and MI among Africans. Our findings provide empirical evidence that SELE genetic polymorphisms may contribute to the pathogenesis of CHD and MI, especially among Asians and Caucasians. Thus, SELP genetic polymorphisms could be potential and practical biomarkers for early diagnosis of CHD and MI.     

Genetic association of lipid metabolism related SNPs with myocardial infarction in the Pakistani population

Myocardial infarction (MI) is the major cardiovascular disease. This can be caused by mutual interaction of environmental and genetic factors. The current study was designed to investigate the role of lipid metabolism related genetic polymorphisms with the onset of MI in Punjabi population of Pakistan. A total of 384 subjects was studied from April 2011 to July 2012. To determine the genetic associations with MI, the single nucleotide polymorphisms (SNPs) were genotyped by sequencing, as well as one label extension method. Out of eight SNPs in four candidate genes, seven genetic variants were significantly (P < 0.05) associated with elevated risk of MI. In current study two SNPs rs662799 risk allele G (P = 0.03) and rs3135506 risk allele C (P = 0.05) of APOA5 were found to be associated with significant higher risk of triglyceride levels, irrespective of age, sex, obesity, diabetes, hypertension and smoking. Gene variants (rs1558861, rs662799 and rs10750097) in APOA5 showed almost complete linkage disequilibrium and their minor allele frequencies (0.34, 0.28, and 0.41 respectively) were more prevalent (P < 0.05) in cases than controls. We further revealed risk haplotypes (C-T-G-A, G-C-A-G; P = 0.001) and protective haplotypes (G-T-A-G, C-C-G-A; P = 0.005) between these four SNPs for the progression of MI. Current study confirms the correlation between lipid metabolism related SNPs with MI and supports the role of APOA5 in raising plasma triglyceride levels in Pakistanis. However further studies are needed for delineating the role of these SNPs.     

Association of genetic polymorphisms in ADH and ALDH2 with risk of coronary artery disease and myocardial infarction: A meta-analysis

Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are the major enzymes responsible for alcohol metabolism in humans. Emerging evidences have shown that functional polymorphisms in ADH and ALDH genes might play a critical role in increasing coronary artery disease (CAD) and myocardial infarction (MI) risks; however, individually published studies showed inconclusive results. The aim of this meta-analysis is to evaluate the associations between the genetic polymorphisms of ADH and ALDH genes with susceptibility to CAD and MI. A literature search was conducted on PubMed, Embase, Web of Science and Chinese BioMedical databases from inception through December 1st, 2012. Crude relative risks (RRs) with 95% confidence intervals (CIs) were calculated. Twelve case–control studies were included with a total of 9616 subjects, including 2053 CAD patients, 1436 MI patients, and 6127 healthy controls. Meta-analysis showed that mutant genotypes (GA + AA) of the rs671 polymorphism in the ALDH2 gene were associated with increased risk of both CAD and MI (CAD: RR = 1.20, 95%CI: 1.03–1.40, P = 0.021; MI: RR = 1.32, 95%CI: 1.11–1.57, P = 0.002). However, there were no significant associations of ADH genetic polymorphisms to CAD and MI risks (CAD: RR = 0.92, 95%CI: 0.73–1.15, P = 0.445; MI: RR = 0.93, 95%CI: 0.84–1.03, P = 0.148). In conclusion, this meta-analysis provides strong evidence that ALDH2 rs671 polymorphism may be associated with increased risks of CAD and MI. However, further studies are still needed to accurately determine whether ADH genetic polymorphisms are associated with susceptibility to CAD and MI.     

ADRB2 polymorphisms predict the risk of myocardial infarction and coronary artery disease

Recently, the rs1042713 G > A and rs1042714 C > G polymorphisms in the beta-2 adrenergic receptor (ADRB2) gene were shown to be related to atherosclerosis diseases. Therefore, we performed a systemic meta-analysis to determine whether the two functional polymorphisms are related to the risk of myocardial infarction (MI) and coronary artery disease (CAD). We identified published studies that are relevant to our topic of interest. Seven case-control studies, with a total of 6,843 subjects, were incorporated into the current meta-analysis. Our analysis showed a higher frequency of rs1042713 G > A variant in patients with MI or CAD compared to healthy controls. A similar result was also obtained with the rs1042714 C > G variant under both the allele and dominant models. Ethnicity-stratified subgroup analysis suggested that the rs1042714 C > G variant correlated with an increased risk of the two diseases in both Asians and Caucasians, while rs1042713 G > A only contributes to the risk of two diseases in Asians. In the disease type-stratified subgroups, the frequencies of both the rs1042713 G > A and rs1042714 C > G variants were higher in the cases than in the controls in both the MI and CAD subgroups. Collectively, our data contribute towards understanding the correlation between the rs1042713 G > A and rs1042714 C > G polymorphisms in ADRB2 and the susceptibility to MI and CAD.     

A novel major histocompatibility complex locus confers the risk of premature coronary artery disease in a Chinese Han population

Several novel loci have been proved to be associated with coronary artery disease and/or myocardial infarction risk by genome-wide association studies, however, the available coronary artery disease risk variants explain only a small proportion of the predicted genetic heritability of the disease. Recently, a novel coronary artery disease locus on chromosome 6p21.3 in the major histocompatibility complex was identified in an European population. We hereby investigated whether this single nucleotide polymorphisms (rs3869109) confers the risk of premature coronary artery disease in a Chinese Han population. A total of 422 patients were studied including 210 cases with coronary stenosis ≥50 % or previous myocardial infarction (male <55 years and female <65 years) and 212 controls without documented coronary artery disease. Ligase detection reaction was performed to detect rs3869109. The 3 genotypes AA, AG, and GG were present in rs3869109. There were significant differences between the control and premature coronary artery disease groups in the frequencies of the rs3869109 variants and alleles (all P < 0.05). The distribution of 3 genotypes and alleles at rs3869109 does not differ between women and men (all P > 0.05). There was a significant association between rs3869109 genotypes and the severity of premature coronary artery disease (P = 0.038). Multivariate logistic regression showed that carriers with AG and GG genotypes at rs3869109 have a higher risk of premature coronary artery disease than carriers of AA genotype (odds ratio [OR] 1.997, 95 % CI: 1.166–3.419, P = 0.012; OR 1.695, 95 % CI: 1.044–2.752, P = 0.033; respectively). Our results indicate that the rs3869109 variants are associated with premature coronary artery disease in a Chinese Han population, suggesting this genetic risk marker is useful in early coronary artery disease risk prediction.     

A TagSNP in SIRT1 Gene Confers Susceptibility to Myocardial Infarction in a Chinese Han Population

SIRT1 exerts protective effects against endothelial cells dysfunction, inflammation and atherosclerosis, indicating an important role on myocardial infarction (MI) pathogenesis. Nonetheless, the effects of SIRT1 variants on MI risk remain poorly understood. Here we aimed to investigate the influence of SIRT1 polymorphisms on individual susceptibility to MI. Genotyping of three tagSNPs (rs7069102, rs3818292 and rs4746720) in SIRT1 gene was performed in a Chinese Han population, consisting of 287 MI cases and 654 control subjects. In a logistic regression analysis, we found that G allele of rs7069102 had increased MI risk with odds ratio (OR) of 1.57 [95% confidence interval (CI) = 1.15–2.16, Bonferroni corrected P (P_c) = 0.015] after adjustment for conventional risk factors compared to C allele. Similarly, the combined CG/GG genotypes was associated with the increased MI risk (OR = 1.64, 95% CI = 1.14–2.35, P_c = 0.021) compared to the CC genotype. Further stratified analysis revealed a more significant association with MI risk among younger subjects (≤ 55 years old). Consistent with these results, the haplotype rs7069102G-rs3818292A-rs4746720T containing the rs7069102 G allele was also associated with the increased MI risk (OR = 1.41, 95% CI = 1.09–1.84, P_c = 0.040). However, we did not detect any association of rs3818292 and rs4746720 with MI risk. Our study provides the first evidence that the tagSNP rs7069102 and haplotype rs7069102G-rs3818292A-rs4746720T in SIRT1 gene confer susceptibility to MI in the Chinese Han population.     

Relationships of LDLR genetic polymorphisms with cerebral infarction: a meta-analysis

This meta-analysis was undertaken to identify the relationships between genetic polymorphisms in the LDLR gene and the risk of cerebral infarction. The Web of Science (1945–2013), the Cochrane Library Database (Issue 12, 2013), PubMed (1966–2013), EMBASE (1980–2013), CINAHL (1982–2013) and the Chinese Biomedical Database (CBM) (1982–2013) were searched for relevant articles without language restrictions. Meta-analysis was conducted using the STATA 12.0 software. Crude odds ratios (OR) with their corresponding 95 % confidence interval (CI) were calculated. Eight case–control studies with a total of 4,655 patients with cerebral infarction and 15,920 healthy control subjects were included in our meta-analysis. Five common polymorphisms in the LDLR gene were evaluated, including rs11669576 A > T, rs1433099 C > T, rs5925 C > T, rs688 C > T, rs1122608 T > G in the LDLR gene. The results of this meta-analysis revealed that cerebral infarction patients had a higher frequency of LDLR genetic polymorphisms than that of healthy controls (allele model: OR 1.17, 95 % CI 1.05–1.30, P = 0.004; dominant model: OR 1.18, 95 % CI 1.05–1.33, P = 0.007; homozygous model: OR 1.50, 95 % CI 1.03–2.16, P = 0.032; respectively), especially for the rs11669576 A > T, rs1433099 C > T and rs5925 C > T polymorphisms. Among different ethnic subgroups, the results demonstrated positive correlations between LDLR genetic polymorphisms and an increased risk of cerebral infarction among both Asians and Caucasians under the allele and dominant models (all P < 0.05). Our findings indicate that LDLR genetic polymorphisms may be strongly involved in the pathogenesis of cerebral infarction, especially the rs11669576 A > T, rs1433099 C > T, rs5925 C > T polymorphisms.     

Association of Genetic Variants of MTHFR,ENPP1, and ADIPOQ with Myocardial Infarction in Egyptian Patients

The study aimed to investigate the association between MTHFR C677T, ENPP1 K121Q, and ADIPOQ 45 T/G gene polymorphisms and incidence of myocardial infarction (MI) in Egyptian patients. The study included 60 unrelated patients suffering from their first MI and 60 unrelated controls. Patients were recruited from Kasr-El Eini hospital, Cairo University. The previously mentioned polymorphisms were determined in all participants by PCR–RFLP. There was no significant difference in the distribution of genotypes and alleles of MTHFR C677T between groups. In contrast, significant difference was found in the distributions of genotypes and alleles of ENPP1 K121Q and ADIPOQ 45 T/G between MI patients and controls (P = 0.01, P = 0.004, P = 0.009, P = 0.001, respectively). Univariate analysis revealed that 121Q ENPP1 and 45 G ADIPOQ alleles were associated with the increased risk of MI (OR = 3; 95 % CI = 1.45–6.2; P = 0.004 and OR = 5.8; 95 % CI = 1.92–17.54; P = 0.001, respectively). The mutant homozygous genotypes of MTHFR, ENPP1, and ADIPOQ were more prevalent in diabetic hypertensive MI patients than it was among non-diabetic normotensive MI patients. Regarding the coagulation profile, INR (P = 0.009) and PC % (P = 0.022) were significantly different among the three genotypes of MTHFR C677T. The 677 T, 121 Q, and 45G variants were associated with MI in Egyptian patients; however, more studies are needed to determine the possible protective effect for these polymorphisms in our population.     

Chromosome 9p21 rs10757278 polymorphism is associated with the risk of metabolic syndrome

Metabolic syndrome (MetS) is a common multifactorial disorder that involves abdominal obesity, dyslipidemia, hypertension, and hyperglycemia. Genome-wide association studies have identified a major risk locus for coronary artery disease and myocardial infarction on chromosome 9p21. Here, we examined the frequency of single nucleotide polymorphisms (SNPs) on chromosome 9p21 in a sample of Turkish patients with MetS and further investigated the correlation between regional SNPs, haplotypes, and MetS. The real-time polymerase chain reaction (RT-PCR) was used to analyze 4 SNPs (rs10757274 A/G, rs2383207 A/G, rs10757278 A/G, rs1333049 C/G) in 291 MetS patients and 247 controls. Analysis of 4 SNPs revealed a significant difference in the genotype distribution for rs2383207, rs10757278, and rs1333049 between MetS patients and controls (p = 0.041, p = 0.005, p = 0.023, respectively) but not for rs10757274 (p = 0.211). MetS and control allelic frequencies for rs2383207, rs10757278, and rs1333049 were statistically different (p < 0.05). The rs2383207 AG variant, was identified as a MetS risk factor (p = 0.012, OR = 33.271; 95 % CI: 2.193–504.805) and the AA haplotype in block 1 and the GC, AG haplotypes in block 2 were associated with MetS (χ ² = 3.875, p = 0.049; χ ² = 9.334, p = 0.0022; χ ² = 9.134, p = 0.0025, respectively). In this study, we found that chromosome 9p21 SNP rs10757278 and related haplotypes correlate with MetS risk. This is the first report showing an association between a 9p21 variant and MetS and suggests that rs10757278 polymorphism may confer increased risk for disease.     

Correlations of SELE and SELP genetic polymorphisms with myocardial infarction risk: a meta-analysis and meta-regression

This meta-analysis was undertaken in an attempt to understand the relationships of functional polymorphisms in the SELE and SELP genes to myocardial infarction (MI) risk. The PubMed, CISCOM, CINAHL, Web of Science, Google Scholar, EBSCO, Cochrane Library, and CBM databases were searched for relevant articles published before March 1st, 2013 without any language restrictions. Meta-analysis was conducted using the STATA 12.0 software. Crude odds ratios with 95 % confidence intervals were calculated. The effect of SELE and SELP genetic polymorphisms on the pathogenesis of MI was investigated in this meta-analysis with a total of ten case–control studies, including 2,696 MI patients and 4,724 healthy subjects. Eight single nucleotide polymorphisms were assessed, including polymorphisms 98G/T, 128S/R and 561A/C in the SELE gene, and polymorphisms 715T/P, 599V/L, 290S/N, 562N/D and 2123G/C in the SELP gene. The results of our meta-analysis suggested that SELE genetic polymorphisms might be correlated with an increased risk of MI, especially for 128S/R and 561A/C polymorphisms. A subgroup analysis by ethnicity was conducted to investigate its effects on susceptibility to MI. The results revealed positive significant correlations between SELE genetic polymorphisms and the risk of MI among Asians, but not among Caucasians (all P > 0.05). Nevertheless, no significantly correlations were found between SELP genetic polymorphisms and MI risk (all P > 0.05). In the subgroup analysis by ethnicity, we also did not observe significant associations between SELP genetic polymorphisms and MI risks among both Asians and Caucasians (all P > 0.05). The current meta-analysis suggests that SELE genetic polymorphisms may contribute to the development of MI, especially for the 128S/R and 561A/C polymorphisms among Asians. However, SELP genetic polymorphisms may not be important risk factors in MI.     

VKORC1 rs2359612C allele is associated with increased risk of coronary artery disease in the presence of coronary calcification

VKORC1 genetic polymorphisms affect warfarin dose response, aortic calcification, and the susceptibility of coronary artery disease as shown in our previous study. Little is known regarding the association of VKORC1 polymorphisms with coronary artery calcification (CAC) and the role of CAC in the association with coronary artery disease (CAD). Due to a natural haplotype block in the VKORC1 gene in Chinese, polymorphism rs2359612 was analyzed in a case–control study and a prospective study. The case–control study included 464 CAD patients with non-calcified plaque (NCP), 562 CAD patients with mixed calcified plaque (MCP), 492 subjects with calcified plaque (CP), and 521 controls. The rs2359612C was only associated with increased risk of MCP, the CAD in the presence of CAC; the odds ratio was 1.397 (95 % CI 1.008–1.937, P < 0.05), which was replicated in the second independent population. On the contrary, a negative correlation was observed between rs2359612 and log-transformed Agatston score, and rs2359612 was negatively associated with the number of calcified vessels. Moreover, in a prospective study including 849 CAD patients undergoing revascularization, rs2359612C predicted a higher incidence of cardiovascular events in MCP subgroup; the relative risk was 1.435 (95 % CI 1.008–2.041, P = 0.045), which was not observed in the NCP subgroup. We conclude that the rs2359612C was associated with a higher risk of CAD in the presence of CAC and a higher incidence of cardiovascular events in CAD patients with CAC, but a lower coronary calcification. VKORC1 polymorphisms may be associated with the endophenotype of CAD, calcification-related atherosclerosis.     

Higher incidence of death in multi-vessel coronary artery disease patients associated with polymorphisms in chromosome 9p21

ABSTRACT: OBJECTIVE: We investigated whether 9p21 polymorphisms are associated with cardiovascular events in a group of 611 patients enrolled in the Medical, Angioplasty or Surgery Study II (MASS II), a randomized trial comparing treatments for patients with coronary artery disease (CAD) and preserved left ventricular function. METHODS: The participants of the MASS II were genotyped for 9p21 polymorphisms (rs10757274, rs2383206, rs10757278 and rs1333049). Survival curves were calculated with the Kaplan-Meier method and compared with the log-rank statistic. We assessed the relationship between baseline variables and the composite end-point of death, death from cardiac causes and myocardial infarction using a Cox proportional hazards survival model. RESULTS: We observed significant differences between patients within each polymorphism genotype group for baseline characteristics. The frequency of diabetes was lower in patients carrying GG genotype for rs10757274, rs2383206 and rs10757278 (29.4%, 32.8%, 32.0%) compared to patients carrying AA or AG genotypes (49.1% and 39.2%, p= 0.01; 52.4% and 40.1%, p= 0.01; 47.8% and 37.9%, p= 0.04; respectively). Significant differences in genotype frequencies between double and triple vessel disease patients were observed for the rs10757274, rs10757278 and rs1333049. Finally, there was a higher incidence of overall mortality in patients with the GG genotype for rs2383206 compared to patients with AA and AG genotypes (19.5%, 11.9%, 11.0%, respectively; p= 0.04). Moreover, the rs2383206 was still significantly associated with a 1.75-fold increased risk of overall mortality (p= 0.02) even after adjustment of a Cox multivariate model for age, previous myocardial infarction, diabetes, smoking and type of coronary anatomy. CONCLUSION: Our data are in accordance to previous evidence that chromosome 9p21 genetic variation may constitute a genetic modulator in the cardiovascular system in different scenarios, including in patients with established CAD, by revealing an association between the rs2383206 and higher incidence of overall mortality and death from cardiac causes in patients with multi-vessel CAD.     

Multi-allelic haplotype association identifies novel information different from single-SNP analysis: A new protective haplotype in the LRP8 gene is against familial and early-onset CAD and MI

Our previous studies identified a functional SNP, R952Q in the LRP8 gene, that was associated with increased platelet activation and familial and early-onset coronary artery disease (CAD) and myocardial infarction (MI) in American and Italian Caucasian populations. In this study, we analyzed four additional SNPs near R952Q (rs7546246, rs2297660, rs3737983, rs5177) to identify a specific LRP8 SNP haplotype that is associated with familial and early-onset CAD and MI. We employed a case–control association design involving 381 premature CAD and MI probands and 560 controls in GeneQuest, 441 individuals from 22 large pedigrees in GeneQuest II, and 248 MI patients with family history and 308 controls in an Italian cohort. Like R952Q, LRP8 SNPs rs7546246, rs2297660, rs3737983, and rs5177 were significantly associated with early-onset CAD/MI in both population-based and family-based association studies in GeneQuest. The results were replicated in the GeneQuest II family-based population and the Italian population. We then carried out a haplotype analysis for all five SNPs including R952Q. One common haplotype (TCCGC) was significantly associated with CAD (P = 4.0 × 10^− 11) and MI (P = 6.5 × 10^− 12) in GeneQuest with odds ratios of 0.53 and 0.42, respectively. The results were replicated in the Italian cohort (P = 0.004, OR = 0.71). The sib-TDT analysis also showed significant association between the TCCGC haplotype and CAD in GeneQuest II (P = 0.001). These results suggest that a common LRP8 haplotype TCCGC confers a significant protective effect on the development of familial, early-onset CAD and/or MI.     

The maternal folate hydrolase gene polymorphism is associated with neural tube defects in a high-risk Chinese population

Folate hydrolase 1 (FOLH1) gene encodes intestinal folate hydrolase, which regulates intestinal absorption of dietary folate. Previous studies on the association between polymorphisms rs202676 and rs61886492 and the risk of neural tube defects (NTDs) were inconclusive. A case–control study of women with NTD-affected pregnancies (n = 160) and controls (n = 320) was conducted in the Chinese population of Lvliang, a high-risk area for NTDs. We genotyped the polymorphic sites rs202676 and rs61886492 and assessed maternal plasma folate and total homocysteine (tHcy). Our results showed that in case group, plasma folate concentrations were 18 % lower compared with those of control group (8.32 vs. 6.79 nmol/L, p = 0.033) and tHcy concentrations were 17 % higher (10.47 vs. 12.65 μmol/L, p = 0.047). Almost all samples had the rs61886492 GG genotype (99.78 %). The result showed that the frequency of GG genotype in rs202676 was significantly higher in group with multiple NTDs than in controls (p = 0.030, OR = 2.157, 95 % CI, 1.06–4.38). The multiple-NTD group showed higher maternal plasma concentrations of tHcy (10.47 vs. 13.96 μmol/L, p = 0.024). The GG genotype of rs202676 had a lower maternal folate and higher tHcy concentrations than other genotypes with no significant differences. The result of structural prediction indicated that this variation might change the spatial structure of the protein. These results suggested that the maternal polymorphism rs202676 was a potential risk factor for multiple NTDs in this Chinese population. The allele G might affect maternal plasma folate and tHcy concentration.     

A polymorphism in the visfatin gene promoter is related to decreased plasma levels of inflammatory markers in patients with coronary artery disease

Visfatin, a newly identified proinflammatory adipokine, has been linked to coronary artery disease (CAD). The ?1535C>T polymorphism (rs61330082) located in the visfatin gene promoter is reportedly associated with proinflammatory status. However, it is unclear whether this polymorphism correlates with plasma levels of inflammatory markers including visfatin, hs-CRP, IL-6 and TNF-?? in CAD patients. The present study was to investigate the potential association of the ?1535C>T polymorphism with plasma levels of visfatin, IL-6, C reactive protein (hs-CRP) and TNF-?? in patients with CAD. We conducted a hospital based study with 171 CAD patients to examine the association between the ?1535C>T polymorphism and plasma levels of visfatin, hs-CRP, IL-6 and TNF-??. Plasma visfatin levels were markedly different between patients with stable angina pectoris (SAP, 11.91 ± 0.70 ng/l) and those with unstable angina pectoris (UAP, 17.49 ± 0.20 ng/l) or acute myocardial infarction (AMI, 16.63 ± 0.22 ng/l; SAP versus UAP or AMI, P < 0.05). Compared with the CC genotype, variant genotypes CT and TT correlated with significantly lower levels of visfatin, hs-CRP, IL-6 and TNF-?? in the SAP group (P < 0.05), with lower levels of hs-CRP and IL-6 in the UAP group (P < 0.05), and with lower levels of visfatin in the AMI group (P < 0.05) after adjustment for age, gender, smoking, hypertension, diabetes, dyslipidemia and medication. Our results suggest that the ?1535C>T polymorphism is associated with decreased plasma levels of inflammatory markers in CAD patients, reflecting that this polymorphism might provide a useful marker for predicting the development of CAD events.     

Association between inflammatory gene polymorphisms and the risk of myocardial infarction

Allele and genotype frequency distributions of polymorphism rs2076059 (3832T>C) within the SELE gene, rs6131 (S290N), within the SELP gene, rs1131498 (F206L), within the SELL gene, rs5498 (K469E) within the ICAM1 gene, rs35569394 (?2549(18)I/D) within the VEGFA gene, and rs1024611 (?2518A>G) within the CCL2 gene were examined in a group of patients after myocardial infarction (MI)(280 individuals) and in a control group (312 individuals). An implementation of the Markov chain and Monte-Carlo method (APSampler) revealed the allele combinations associated with decreased and increased risk of MI. Among these, the most important allele combinations were SELE*C + SELP*S + CCL2*A (FDR = 0.0005; OR = 0.42), SELP*S + CCL2*A (FDR = 0.0009; OR = 0.36), SELL*F + VEGFA*I + CCL2*G/G (FDR = 0.0009; OR = 4.17), VEGFA*I + CCL2*G/G (FDR = 0.0009; OR = 3.76), SELE*C + CCL2*A (FDR = 0.0023; OR = 0.47), and SELL*F + CCL2*G/G (FDR = 0.003; OR = 3.15).     

Association between PIN1 promoter polymorphisms and risk of nasopharyngeal carcinoma

Peptidylprolyl cis/trans isomerase, NIMA-interacting 1 (PIN1) plays an important role in cell transformation and oncogenesis. Association between PIN1 promoter polymorphisms and cancer risk was reported in several cancers. This study aimed to evaluate the association between two single nucleotide polymorphisms (SNPs, ?667T>C, rs2233679 and ?842G>C, rs2233678) on PIN1 promoter and risk of nasopharyngeal carcinoma (NPC). The two SNPs were genotyped using polymerase chain reaction-restriction fragment length polymorphism in a total of 334 native Chinese subjects consisting of 178 cases and 156 controls. The results indicated that the ?667CT heterozygote and ?667CC homozygote exhibited a significantly decreased risk of nasopharyngeal carcinoma when compared with ?667TT homozygote (OR = 0.639, 95 % CI = 0.452–0.903, p = 0.011 for ?667CT; and OR = 0.441, 95 % CI = 0.213–0.915, p = 0.038 for ?667CC, respectively). In the ?842G>C polymorphism, compared with ?842GG homozygote, only ?842CG heterozygote but not ?842CC homozygote had a significantly decreased risk of nasopharyngeal carcinoma (OR = 0.465, 95 % CI = 0.249–0.871, p = 0.010). Genotype in the two SNPs in patients showed no significant associations with the clinicopathologic features examined. Our study showed that the minor genotypes of PIN1 promoter (?667CT, ?667CC and ?842CG) were associated with decreased risk of NPC in a Chinese population, suggested that PIN1 promoter polymorphisms might play an important role in NPC carcinogenesis.