Correlations of SELE genetic polymorphisms with risk of coronary heart disease and myocardial infarction: a meta-analysis

This meta-analysis of case–control studies was conducted to determine whether SELE genetic polymorphisms contribute to the pathogenesis of coronary heart disease (CHD) and myocardial infarction (MI). The PubMed, CISCOM, CINAHL, Web of Science, Google Scholar, EBSCO, Cochrane Library, and CBM databases were searched for relevant articles published before November 1st, 2013 without any language restrictions. Meta-analysis was conducted using the STATA 12.0 software. Twenty case–control studies met the inclusion criteria, with a total of 2,292 CHD patients, 901 MI patients and 3,233 healthy controls. Six common polymorphisms in the SELE gene were evaluated, including 554L/F, 98G/T, 128S/R, 2692G/A, 1901C/T, and 1856A/G. The results of our meta-analysis suggest that SELE genetic polymorphisms might be strongly correlated with an increased risk of CHD (allele model: OR 2.08, 95 % CI 1.67–2.58, P < 0.001; dominant model: OR 2.12, 95 % CI 1.68–2.68, P < 0.001; respectively), especially the SELE 554L/F, 98G/T and 128S/R polymorphisms. Furthermore, our findings indicated that SELE genetic polymorphisms were closely linked to the risk of CHD in Asians but not Caucasians. However, our findings reveal no positive correlations between SELE genetic polymorphisms and MI risk (allele model: OR 1.39, 95 % CI 1.00–1.94, P = 0.054; dominant model: OR 1.40, 95 % CI 0.96–2.04, P = 0.081; respectively). The current meta-analysis suggests that SELE genetic polymorphisms may contribute to an increased risk of CHD, especially the SELE 554L/F, 98G/T and 128S/R polymorphisms in Asians. However, SELE genetic polymorphisms may not be important determinants of susceptibility to MI.     

The effect of PPARG gene polymorphisms on the risk of coronary heart disease: a meta-analysis

The peroxisome proliferator-activated receptor-γ (PPARG) is a member of the nuclear hormone receptor superfamily that has attracted considerable attention as a candidate gene for coronary heart disease (CHD) based on its function as a key factor involved in the regulation of lipid and glucose metabolism. In the past decade, a number of case–control studies have been carried out to investigate the relationship between the PPARG polymorphisms and CHD. However, these studies have yielded contradictory results. To derive a more precise estimation of the relationship, a meta-analysis of 33 studies including a total of 12,340 cases and 17,471 controls on 3 PPARG polymorphisms (Pro12Ala, C161T and C1431T) was performed. In a combined analysis, the summary per-allele odds ratio for CHD was 1.02 (95 % CI: 0.93–1.13), 0.86 (95 % CI: 0.72–1.02), and 0.92 (95 % CI: 0.74–1.16) for PPARG 12Ala, 161T and 1431T alleles, respectively. No significant results were observed under dominant or recessive genetic models for these polymorphisms in almost all comparisons. In the stratified analyses according to ethnicity, sample size, CHD endpoints and HWE status, no evidence of any gene-disease association was obtained. Our results suggest that the Pro12Ala, C161T and C1431T polymorphisms of PPARG gene are not associated with CHD susceptibility.     

Cytomegalovirus infection and coronary heart disease risk: a meta-analysis

The chronic inflammatory process including cytomegalovirus (CMV) infection has been hypothesized to induce the progression of atherosclerosis in coronary heart disease (CHD). Numbers studies were conducted to analyze the association between CMV infection and risk of CHD, but no clear consensus had been reached. To assess this relationship more precisely, a meta-analysis was performed. The electronic databases PubMed, Embase, and CNKI were searched; data were extracted and analyzed independently by two investigators. Ultimately, 55 studies, involving 9,000 cases and 8,608 controls from six prospective studies (all with a nested case–control design) and 49 retrospective case–control studies were included. Overall, people exposed to CMV infection had an odds ratio (OR) of 1.67 (95% CI, 1.56–1.79) for CHD risk, relative to those not exposed. CMV infection was clearly identified as a risk factor for CHD in both prospective studies (OR, 1.31; 95% CI, 1.132–1.517) and retrospective studies (OR, 1.79; 95% CI, 1.659–1.939), and in both Asian group (OR, 2.69; 95% CI, 2.304–3.144) and non-Asian group (OR, 1.48; 95% CI, 1.371–1.600). Interestingly, in the subgroup analyses by detection methods of CMV, the increased risk (OR, 8.121) was greater among studies using polymerase chain reaction than the risk (OR, 1.561) among studies using enzyme-linked immunosorbent assay. In conclusion, this meta-analysis suggested that CMV infection is associated with an increased risk for CHD, especially among Asian populations.     

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.     

Matrix metalloproteinase-1 gene polymorphisms and periodontitis susceptibility: A meta-analysis based on 11 case-control studies

Matrix metalloproteinase-1 has been implicated in periodontal disease, but the association between the most-studied Matrix metalloproteinase-1 1G-to-2G polymorphism and the risk of periodontal disease were reported with inconclusive results. Therefore, the aim of this study was to investigate the association between the Matrix metalloproteinase-1 1G-to-2G polymorphism and periodontal disease. Electronic databases search yielded 11 studies with 1447 patients and 1710 control subjects evaluated the association of the polymorphisms of Matrix metalloproteinase-1 1G-to-2G and periodontitis risk were brought into this study. The association was evaluated by odds ratio (OR) and its 95% confidence interval (CI). The overall results showed that the variant genotypes were associated with a significantly increased risk of periodontitis (OR = 1.45, 95% CI = 1.02–1.26 for 2G/2G vs 1G/1G, and OR = 2.27, 95% CI = 1.22–4.23 for 2G/2G vs 1G/2G + 1G/1G). In the stratified analyses, there was a significantly increased risk for the studies of periodontitis (OR = 1.59, 95% CI = 1.15–2.21 for 2G/2G vs 1G/1G; OR = 3.48, 95% CI = 1.39–8.71 for 2G/2G vs 1G/2G + 1G/1G), which remained for the studies of Asian populations. And there was a significantly increased risk of severe periodontitis (OR = 2.15, 95% CI = 1.35–3.43 for 2G/2G vs 1G/1G; OR = 2.86, 95% CI = 1.31–2.64 for 2G/2G vs 1G/2G + 1G/1G; OR = 1.6, 95% CI = 1.12–2.39 for 1G/2G + 2G/2G vs 1G/1G; OR = 1.61, 95% CI = 1.28–2.03 for 2G allele vs 1G allele). The current study demonstrated that the Matrix metalloproteinase-1-1607 1G-to-2G polymorphism was associated with susceptibility to periodontitis, apparently, severe periodontitis.     

GSTT1 null genotype contributes to coronary heart disease risk: a meta-analysis

Many studies have investigated the association between glutathione S-transferase T1 (GSTT1) null genotype and risk of coronary heart disease (CHD), but the impact of GSTT1 null genotype on CHD is still unclear owing to the obvious inconsistence among those studies. This study aims to quantify the strength of association between GSTT1 null genotype and risk of CHD. We searched the PubMed, Embase and Wangfang databases for studies relating the association between GSTT1 null genotype and risk of CHD. We estimated summary odds ratio (OR) with their 95 % confidence interval (95 % CI) to assess the association. 24 case-control studies with 13, 884 CHD cases and 30, 719 controls were included into this meta-analysis. Meta-analysis of total 24 studies showed GSTT1 null genotype was not associated risk of CHD (random-effects OR = 1.17, 95 % CI 0.97-1.42, P = 0.101). After adjustment for heterogeneity, meta-analysis showed GSTT1 null genotype was associated increased risk of CHD both in total population and Caucasians (for total population, fixed-effects OR = 1.12, 95 % CI 1.05-1.21, P = 0.001; for Caucasians, fixed-effects OR = 1.10, 95 % CI 1.02-1.19, P = 0.010). There was no significant association in the other populations. No evidence of publication bias was observed. Meta-analyses of available data suggest the GSTT1 null genotype contributes to increased risk of CHD in Caucasians.     

C-reactive protein (CRP) gene polymorphisms, CRP levels, and risk of incident coronary heart disease in two nested case-control studies

Background

C-reactive protein (CRP), an acute phase reactant and marker of inflammation, has been shown to predict risk of incident cardiovascular events. However, few studies have comprehensively examined six common single-nucleotide polymorphisms (SNPs) in the CRP gene, haplotypes, and plasma CRP levels with risk of coronary heart disease (CHD).

Methods and Findings

We conducted parallel nested case-control studies within two ongoing, prospective cohort studies of U.S. women (Nurses'' Health Study) and men (Health Professionals Follow-up Study). Blood samples were available in a subset of 32,826 women and 18,225 men for biomarker and DNA analyses. During 8 and 6 years of follow-up, 249 women and 266 men developed incident nonfatal myocardial infarction or fatal CHD, and controls (498 women, 531 men) were matched 2:1 on age, smoking, and date of blood draw from participants free of cardiovascular disease at the time the case was diagnosed. Among both women and men, minor alleles were significantly associated with higher CRP levels for SNPs 1919A>T and 4741G>C, but associated with lower CRP levels for SNPs 2667G>C and 3872C>T. SNP 2667G>C was individually associated with increased risk of CHD in both women [OR 1.57 (95% CI 1.01–2.44); p = 0.047] and men [1.93 (95% CI 1.30–2.88); p = 0.001]. Two of the five common haplotypes were associated with lower CRP levels, and Haplotype 4 which included minor alleles for 2667 and 3872 was associated with significantly lower CRP levels and an elevated risk of CHD. The remaining SNPs or haplotypes were not associated with CHD in both populations.

Conclusions

Common variation in the CRP gene was significantly associated with plasma CRP levels; however, the association between common SNPs and CRP levels did not correspond to a predicted change in CHD risk. The underlying inflammatory processes which predict coronary events cannot be captured solely by variation in the CRP gene.     

Lipoprotein-associated phospholipase A2 gene V279F polymorphisms and coronary heart disease: a meta-analysis

Lipoprotein-associated phospholipase A2 (LP-PLA2) may play an important role in the pathophysiology of coronary heart disease (CHD). The polymorphism of LP-PLA2 gene caused LP-PLA2 enzyme activity depressing or lost. But there is not a definite conclusion for the association of between the LP-PLA2 gene polymorphism and CHD risk. To assess the relationship between LP-PLA2 gene V279F polymorphism and CHD, a comprehensive Meta-analysis was performed. All the case–control studies evaluating the association of between the LP-PLA2 gene V279F polymorphism and CHD risk were identified. Seven case–control studies involving 3,614 patients with CHD and 4,334 controls were included. The crude odds ratios (ORs) of meta-analysis under the different gene model were not significant. But in the stratified analysis by study size, ethnicity, cases definition, and source of controls under the additive model, the association was evident in ethnicity for Japanese group (OR = 1.38, 95%CI = 1.22–1.56), cases definition for MI (OR = 1.22, 95%CI = 1.01–1.49), source of controls for the based-hospital (OR = 1.42, 95%CI = 1.24–1.59). These data suggested that the V279F polymorphism in LP-PLA2 gene may contribute to CHD development. But there is necessary that more well-designed large studies are required for the validation of this association.     

Interleukin-10 gene polymorphisms and chronic/aggressive periodontitis susceptibility: A meta-analysis based on 14 case-control studies

Interleukin-10 (IL-10) has been described as an anti-inflammatory cytokine and IL-10 gene polymorphisms was associated with altered interleukin-10 levels, therefore, we aimed to conduct a meta-analysis assessing the association of IL-10 genetic polymorphisms with the risk of both chronic periodontitis (CP) and aggressive periodontitis (AgP). Electronic databases were acquired from PubMed, Embase, the Sinomed and WANFANG. Fourteen studies with 1438 patients and 1303 control subjects investigated the association of the three single-nucleotide polymorphisms (SNPs) of IL-10 (-1082A>G, -819C>T, -592C>A) and chronic/aggressive periodontitis risk were brought into this study. We found that there was no association between IL-10 -1082 gene polymorphism and periodontitis risk (either CP or AgP), even when we separately investigated sub-group analysis among Caucasians. The -819 polymorphism seemed to be a genetic risk factor to CP among Caucasians (T allele vs. C allele: OR=1.55, 95%CI=1.07-2.24; CT vs. CC: OR=1.64, 95%CI=1.00-2.67). When excluding one study deviated from HWE, the results showed that the T allele carriers had a significantly risk of CP in overall population (T allele vs. C allele: OR=1.23, 95%CI=1.03-1.48). Furthermore, the results of this meta-analysis showed that -592 polymorphism was associated with a significantly increased risk of CP (A allele vs. C allele: OR=1.38, 95%CI=1.04-1.85; AA vs. CA+CC: OR=1.39, 95%CI=1.05-1.85 for overall analysis; A allele vs. C allele: OR=1.97, 95%CI=1.36-3.86; AA vs. CC: OR=3.70, 95%CI=1.32-10.39; CA vs. CC: OR=2.22, 95%CI=1.36-3.64, AA+CA vs. CC: OR=2.35, 95%CI=1.46-3.79 for Caucasian descent analysis). This meta-analysis suggested that IL-10 -819 and -592 gene polymorphisms were associated with CP, especially among Caucasians. Further research is needed to assess possible gene-gene or gene-environment-lifestyle interactions on periodontal disease..     

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.     

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.     

The effect of KCNJ11 polymorphism on the risk of type 2 diabetes: a global meta-analysis based on 49 case-control studies

Potassium inwardly rectifying channel, subfamily-J, member 11 (KCNJ11) gene encodes Kir6.2 subunits of the adenosine triphosphate (ATP)-sensitive potassium channel involved in glucose-mediated metabolic signaling pathway and has attracted considerable attention as a candidate gene for type 2 diabetes (T2D) based on its function in glucose-stimulated insulin secretion. In the past decade, a number of case-control studies have been conducted to investigate the relationship between the KCNJ11 polymorphisms and T2D. However, these studies have yielded contradictory results. To investigate this inconsistency and derive a more precise estimation of the relationship, we conducted a comprehensive meta-analysis of 64,403 cases and 122,945 controls from 49 published studies. Using the random-effects model, we found a significant association between E23K (rs5219) polymorphism and T2D risk with per-allele odds ratio of 1.13 (95% confidence interval: 1.10-1.15; p<10(-5)). Significant results were found in East Asians and Caucasians when stratified by ethnicity; whereas no significant associations were found among South Asians and other ethnic populations. In subgroup analysis by sample size, mean age and body mass index (BMI) of cases, mean BMI of controls and diagnostic criterion, significantly increased risks were found in all genetic models. This meta-analysis suggests that the E23K polymorphism in KCNJ11 is associated with elevated T2D risk, but these associations vary in different ethnic populations.     

Depression as a risk factor for ischaemic heart disease in men: population based case-control study

Objective: To determine the relation between depression, anxiety, and use of antidepressants and the onset of ischaemic heart disease. Design: Population based case-control study. Setting: All 5623 patients registered with one general practice. Subjects: 188 male cases with ischaemic heart disease matched by age to 485 male controls without ischaemic heart disease; 139 female cases with ischaemic heart disease matched by age to 412 female controls. Main outcome measure: Adjusted odds ratios calculated by conditional logistic regression. Results: The risk of ischaemic heart disease was three times higher among men with a recorded diagnosis of depression than among controls of the same age (odds ratio 3.09; 95% confidence interval 1.33 to 7.21; P=0.009). This association persisted when smoking status, diabetes, hypertension, and underprivileged area (UPA(8)) score were included in a multivariate model (adjusted 2.75; 1.13 to 6.69; P=0.03). Men with depression within the preceding 10 years were three times more likely to develop ischaemic heart disease than were the controls (3.13; 1.27 to 7.70; P=0.01). Men with ischaemic heart disease had a higher risk of subsequent ischaemic heart disease than men without ischaemic heart disease (adjusted 2.34; 1.34 to 4.10; P=0.003). Depression was not a risk factor for ischaemic heart disease in women on multivariate analysis (adjusted 1.34; 0.70 to 2.56; P=0.38). Anxiety and subsequent ischaemic heart disease were not significantly associated in men or women. Conclusion: Depression may be an independent risk factor for ischaemic heart disease in men, but not in women.

Key messages

• So far, research into whether depression precedes myocardial infarction has been limited
• This case-control study examined the relation between ischaemic heart disease and depression and the differences in this relation between men and women
• Depression may be a risk factor for ischaemic heart disease in men but not women
• This is independent of diabetes, hypertension, deprivation score, and smoking status

     

Intercellular adhesion molecule 1 gene K469E polymorphism is associated with coronary heart disease risk: a meta-analysis involving 12 studies

Coronary atherosclerosis is a leading cause of coronary heart disease (CHD). Atherosclerotic lesion is a complex polygenic disease in which gene-environment interactions play a critical role in disease onset and progression. The ICAM1 gene-E469K polymorphism has been reported to be associated with CHD, but results were conflicting. A systematic review and meta-analysis of the published studies were performed to gain a clearer understanding of this association. The PubMed, Embase, and CNKI databases were searched for case–control studies published up to August 2011. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated. Twelve eligible studies, comprising 2,157 cases and 1,952 controls, were included in the meta-analysis. The pooled result showed that the ICAM1 gene-E469K polymorphism was significantly associated with an increased risk of CHD (OR = 1.496, 95% CI = 1.363–1.642, for the allele K vs. allele E; OR = 1.919, 95% CI = 11.635–2.253, for the K allele carriers vs. EE). Subgroup analysis supported the results in the Asian populations and in the Caucasian populations. This meta-analysis suggests that the ICAM1 gene K469E polymorphism is associated with CHD risk and the K allele is a more significant risk factor for developing CHD among Asian and Caucasians populations.     

MTHFR polymorphisms and ovarian cancer risk: a meta-analysis

The C677T and A1298C polymorphisms of methylenetetrahydrofolate reductase (MTHFR) have been reported to alter the risk of ovarian cancer. However, the results are still inconclusive. For better understanding of the effect of these two polymorphisms on ovarian cancer risk, a meta-analysis was performed. An extensive search was performed to identify all case–control studies investigating such association. The strength of association between these two polymorphisms and ovarian cancer risk was assessed by odds ratio (OR) with the corresponding 95?% confidence interval (95?% CI). 3,496 cases and 3,631 controls for C677T polymorphism and 3,280 cases and 3,346 controls for A1298C polymorphism were included in this meta-analysis. The results suggested that there were no significant associations between C677T and A1298C polymorphisms and ovarian cancer risk in overall comparisons in all genetic models (For C677T: TT vs. CC: OR?=?0.94, 95?% CI?=?0.71–1.24, P?=?0.65; CT vs. CC: OR?=?1.03, 95?% CI?=?0.93–1.14, P?=?0.57; TT/CT vs. CC: OR?=?1.01, 95?% CI?=?0.88–1.16, P?=?0.87; TT vs. CC/CT: OR?=?0.93, 95?% CI?=?0.72–1.20, P?=?0.58. For A1298C: CC vs. AA: OR?=?1.05, 95?% CI?=?0.88–1.25, P?=?0.65; CA vs. AA: OR?=?0.98, 95?% CI?=?0.88–1.08, P?=?0.66; CC/CA vs. AA: OR?=?0.99, 95?% CI?=?0.90–1.09, P?=?0.85; CC vs. AA/CA: OR?=?1.06, 95?% CI?=?0.90–1.26, P?=?0.46). Subgroup analysis based on ethnicities and influence analysis did not perturb the results. In conclusion, the results of this meta-analysis indicate that the MTHFR C677T and A1298C polymorphisms are not associated with ovarian cancer risk, especially in Caucasians.     

The association between CD14 gene C-260T polymorphism and coronary heart disease risk: a meta-analysis

Monocyte differentiation antigen CD14 is considered an important cell-activating mediator of inflammatory responses that may result in atherosclerosis, coronary heart disease (CHD), thrombus formation, and myocardial infarction (MI). A common C-260T polymorphism in the promoter of the CD14 gene, the trans-membrane receptor of lipopolysaccharides, has been inconsistently associated with CHD. To investigate this inconsistency, we performed a meta-analysis of 28 studies involving a total of 13,335 CHD cases and 7,979 controls for C-260T of the CD14 gene to evaluate the effect of CD14 on genetic susceptibility for CHD. An overall random effects odds ratio of 1.24 (95 % CI: 1.12–1.36, P < 10^?5) was found for T allele. Significant results were also observed using dominant (OR = 1.34, 95 % CI: 1.17–1.54, P < 10^?4) or recessive genetic model (OR = 1.25, 95 % CI: 1.10–1.41, P = 0.0004). There was strong evidence of heterogeneity (P < 10^?5), which largely disappeared after stratification by ethnicity. After stratified by ethnicity, significant results were found in East Asians; whereas no significant associations were found among Caucasians and other ethnic populations in all genetic models. In the stratified analysis according to sample size, CHD endpoints, and HWE status, significantly increased risks for the polymorphism were found in all genetic models. In conclusion, our results indicate that the CD14 C-260T polymorphism is a risk factor of CHD, especially in East Asians. However, additional very large-scale studies are warranted to confirm our results.