Influence of interleukin-6 gene − 174G>C polymorphism on development of atherosclerosis: A meta-analysis of 50 studies involving 33,514 subjects

Increasing epidemiological studies have focused on the associations between interleukin-6 (IL-6) gene − 174G>C polymorphism and atherosclerotic diseases, but the results are still controversial. This meta-analysis was designed to identify whether this association exists. PubMed, Embase, Web of Science, Cochrane database, Clinicaltrials.gov and Current Controlled Trials, Chinese Clinical Trial Registry, CBMdisc, CNKI and Google Scholar were searched to get the genetic association studies. The crude odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were used to estimate the association between the IL-6 gene − 174G>C polymorphism and atherosclerosis ( AS ) risk. The subgroup analyses were made on the following: ethnicity, atherosclerotic diseases and source of controls. Finally, 50 studies (15,029 cases and 18,485 controls) were included in this meta-analysis. Overall, no significant association was found between the IL-6 gene − 174G>C polymorphism and AS risk (for C allele vs. G allele: OR = 1.02, 95% CI = 0.94–1.11, p = 0.64; for C/C vs. G/G: OR = 1.01, 95% CI = 0.85–1.21, p = 0.88; for C/C vs. C/G + G/G: OR = 0.97, 95% CI = 0.84–1.12, p = 0.68; for C/C + C/G vs. G/G: OR = 1.07, 95% CI = 0.97–1.17, p = 0.18). In the subgroup analyses, significant associations were found between the IL-6 gene − 174G>C polymorphism and AS in non-Caucasian group (for CC + CG vs. GG: OR = 1.22, 95% CI = 1.06–1.41, p = 0.005), other atherosclerotic diseases group (for C allele vs. G allele: OR = 0.75, 95% CI = 0.61–0.93, p = 0.008; for C/C vs. G/G: OR = 0.56, 95% CI = 0.38–0.81, p = 0.002; for C/C vs. C/G + G/G: OR = 0.60, 95% CI = 0.45–0.79, p = 0.0004) and population-based group (for C allele vs. G allele: OR = 1.09, 95% CI = 1.00–1.18, p = 0.04; for CC + CG vs. GG: OR = 1.15, 95% CI = 1.04–1.27, p = 0.005). In summary, the present meta-analysis suggests that the IL-6 gene − 174G C polymorphism is associated with the susceptibility to AS. However, due to the high heterogeneity in the meta-analysis, the results should be interpreted with caution.     

The Relationship between Gene Polymorphism and CRP Level in a Chinese Han Population

We investigated the relationships among the +1444C/T polymorphism in the C-reactive protein (CRP) gene and the concentration of CRP and the risk of coronary heart disease. Using polymerase chain reaction-restriction fragment length polymorphism, we analyzed the frequency distribution of genotypes and alleles of the +1444C/T polymorphism in samples from 128 patients with coronary heart disease (coronary stenosis more than 50%) and 119 unrelated normal individuals. The plasma levels of CRP and lipids in the subjects were also measured. The frequencies of the genotypes were CC 89.1%, CT 10.9%, and TT 0% in patients and CC 89.9%, CT 10.1%, and TT 0% in controls. The frequency of allele C was 94.5% in patients and 95.0% in controls, and allele T was 5.5% in patients and 5.1% in controls. The distribution of genotypes and alleles in the Chinese Han population was significantly different from that of the Caucasian population. There were no significant differences between frequencies of genotype and allele of controls and those of patients (P>0.05), but in controls the concentrations of CRP in the CC genotype subgroup were significantly higher than those in the CT genotype subgroup (P<0.05). This suggests that the +1444C/T variant in the CRP gene influences the basal CRP level in normal people. These findings imply that there may eventually be a need to establish genotype-specific risk thresholds of the CRP level.     

Plasma lecithin:cholesterol acyltransferase activity modifies the inverse relationship of C-reactive protein with HDL cholesterol in nondiabetic men

Lecithin:cholesterol acyltransferase (LCAT) is instrumental in high-density lipoprotein (HDL) maturation, but high LCAT levels do not predict low cardiovascular risk. LCAT may affect antioxidative or anti-inflammatory properties of HDL. We determined the relationship of plasma high-sensitivity C-reactive protein (CRP) with LCAT activity and evaluated whether LCAT activity modifies the decreasing effect of HDL cholesterol (HDL-C) on CRP, as an estimate of its anti-inflammatory properties. Plasma HDL-C, apolipoprotein (apo) A-I and LCAT activity (exogenous substrate method) were measured in 260 nondiabetic men without cardiovascular disease. CRP was correlated inversely with HDL-C and apo A-I, and positively with LCAT activity (P < 0.01 to 0.001). Multivariate regression analysis demonstrated that age- and smoking-adjusted plasma CRP levels were associated negatively with HDL-C (β = − 0.224, P < 0.001) and positively with LCAT activity (β = 0.119, P = 0.034), as well as with the interaction between HDL-C and LCAT activity (β = 0.123, P = 0.026). There was also an interaction between apo A-I and LCAT activity on CRP (β = 0.159, P = 0.005). These relationships remained similar after adjustment for apo B-containing lipoproteins. In conclusion, the inverse relationship of HDL-C with CRP is attenuated by LCAT activity at higher HDL-C levels. It is hypothesized that LCAT could mitigate HDL's anti-inflammatory or antioxidative properties at higher HDL-C concentrations.     

Association of IL-6 − 174G > C and − 572C > G polymorphisms with risk of young ischemic stroke patients

Aim

To investigate the association between interleukin-6 (IL-6) − 174G > C and − 572C > G polymorphisms and risk for ischemic stroke (IS) in young patients.

Methods

We genotyped IL-6  − 174G > C and − 572C > G in a case–control study of 430 young IS patients and 461 control subjects. An unconditional multiple logistical regression model was used to calculate the effects of IL-6 − 174G > C and − 572C > G polymorphisms on IS risk.

Results

Higher body mass index, diabetes, hypertension, obesity, and smoking were associated with risk of ischemic stroke. Multivariate regression analyses showed that subjects carrying the − 174CC genotype (OR = 1.69, 95% CI = 1.16–2.57) and C allele (OR = 1.37, 95% CI = 1.09–1.67) had a small but significant increased risk of IS. Similarly, those carrying the − 572GG genotype (OR = 2.12, 95% CI = 1.18–3.82) and G allele (OR = 1.43, 95% CI = 1.14–1.83) had a moderate increased risk of IS. We found the − 174G > C and − 572C > G polymorphisms interact with hypertension and obesity.

Conclusion

Our results suggest that polymorphisms in IL-6 − 174G > C and − 572C > G are associated with IS risk in young patients, and that these polymorphisms interact with hypertension, obesity and etiologic subtypes. These findings could be helpful in identifying individuals at increased risk for developing IS.     

Polymorphisms of transforming growth factor beta 1 (RS#1800468 and RS#1800471) and esophageal squamous cell carcinoma among Zhuangese population,China

Epidemiological evidence has shown two polymorphisms (namely RS#1800468G > A and RS#1800471G > C) of transforming growth factor-beta 1 (TGF-β1) gene may be involved in the cancer development. However, their role in the carcinogenic process of esophageal squamous cell carcinoma (ESCC) has been less well elaborated. We conducted a hospital-based case-control study including 391 ESCC cases and 508 controls without any evidence of tumors to evaluate the association between these two polymorphisms and ESCC risk and prognosis for Zhuangese population by means of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and amplification refractory mutation system (ARMS)-PCR techniques. We found that individuals with the genotypes with RS#1800471 C allele (namely RS#1800471-GC or -CC) had an increased risk of ESCC than those without above genotypes (namely RS#1800471-GG, adjusted odds ratio 3.26 and 5.65, respectively). Further stratification analysis showed that this polymorphism was correlated with tumor histological grades and TNM (tumor, node, and metastasis) stage, and modified the serum levels of TGF-β1. Additionally, RS#1800471 polymorphism affected ESCC prognosis (hazard ratio, 3.40), especially under high serum levels of TGF-β1 conditions. However, RS#1800468 polymorphism was not significantly related to ESCC risk. These findings indicated that TGF-β1 RS#1800471G > C polymorphism may be a genetic modifier for developing ESCC in Zhuangese population.     

Synergistic effect of anti and pro-inflammatory cytokine genes and their promoter polymorphism with ST-elevation of myocardial infarction

Background

The single-gene approach in association studies of polygenic diseases such as acute myocardial infarction (AMI) is likely to provide limited value. Interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) plasma levels may be genetically influenced.

Aim

We evaluate the impact of single nucleotide polymorphism of the promoter region of these genes, as well as reciprocal interaction of these genes with ST-elevation of myocardial infarction (STEMI).

Methods

In a case–control study 500 STEMI patients and 500 age- and sex-matched controls were studied. Three single-nucleotide polymorphism genotypes were evaluated by polymerase chain reaction and restriction enzyme analysis and assessed their association with STEMI. The synergistic effects of IL-6, TNF-α and IL-10 gene polymorphisms were evaluated by using logistic regression analysis.

Results

We found that IL-6 and TNF-α concentrations of studied population were significantly different (p < 0.0001) in each genotype of IL-6 − 174G>C and TNF-α − 308G>A gene polymorphisms respectively. A significant association was found in multivariate analysis for the IL-6 − 174G>C [odds ratio (OR): 0.390; 95% confidence interval (CI): 0.176–0.865, p = 0.020] and TNF-α − 308G>A [OR: 0.372; 95% CI: 0.171–808, p = 0.012] gene polymorphisms with STEMI. In contrast, IL-10 − 592C>A gene polymorphism was no longer significant in the multivariate model (OR: 0.678; 95% CI: 0.288 to 1.594, p = 0.373) whereas significant in univariate analysis (OR: 0.697; 95% CI: 0.523–0.929, p = 0.014).

Conclusions

Our findings suggest that IL-6, TNF-α and IL-10 gene polymorphisms all contribute in the association with STEMI whereas the association persisted only for IL-6 and TNF-α but not for IL-10 gene polymorphism with this disease in the multivariate analysis.     

Applying DNA barcodes for identification of plant species in the family Araliaceae

Genetic variants of tPA (PLAT) and PAI-1 genes have been suggested to be the risk factors for stroke. In the present case-control study we investigated the association of − 7351 C/T polymorphism (rs2020918) and I/D polymorphism of tPA gene and Insertion/deletion polymorphism (4 G/5 G) of PAI-1 gene with genetic predisposition to ischemic stroke. 516 stroke patients and 513, sex and age matched healthy controls were involved in the study. We did not find a significant association of tPA − 7351 C/T polymorphism and PAI-1 4 G/5 G polymorphism with stroke. However, in case of I/D polymorphism significant difference was observed in the genotypic distribution and allelic frequency between the stroke patients and healthy controls. DD genotype and D allele associated significantly with stroke (p = 0.002 and < 0.001 respectively). We also found significant association of I/D polymorphism with intracranial large artery atherosclerosis and stroke of undetermined etiology. Exploring the association between gene-gene interaction (26 combinations including the three variants) and stroke, we found that individuals with CC + 4G4G + DD, CC + 5G5G + ID, CT + 4G5G + ID, CT + 5G5G + II, CT + 5G5G + ID and TT + 4G5G + II had a significantly higher risk of stroke. The results of this study suggest that − 7351 C/T polymorphism of tPA and 4 G/5 G polymorphism of PAI-1 are not associated with stroke, while as DD genotype and D allele of tPA gene are important risk factors for ischemic stroke. Further we found that the subjects with different tPA and PAI genotype combinations displayed a significantly high risk for overall ischemic stroke suggesting that gene-gene interaction involving more variants may change the susceptibility of particular subjects to the disease.     

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.     

The polymorphism − 1131T > C in apolipoprotein A5 gene is associated with dyslipidemia in Brazilian subjects

Background

Polymorphisms in apolipoprotein A5 gene (APOA5) have been associated with higher triglyceride levels in many populations. The aim of the study was to determine the allelic and genotypic distribution of the APOA5 − 1131T > C polymorphism and to identify the association of the genetic variant and the risk for dyslipidemia.

Methods

We genotyped 109 dyslipidemic subjects and 107 controls. The total cholesterol, triglycerides and HDL-c were determined enzymatically. Comparison of means among groups was calculated by ANOVA. Significant differences among groups were evaluated by Student–Newman–Keuls test.

Results

The minor allele C was more frequent in dyslipidemic subjects than controls (p = 0.019) and confers an increased individual risk for dyslipidemia (OR = 1.726, CI 95% = 1.095–2.721). The genotype analysis by gender showed that this allele was more frequent in dyslipidemic males (p = 0.037; OR = 2.050, CI 95% = 1.042–4.023). When participants were analyzed according to genotypes TT and TC/CC, C-carriers presented higher cholesterol and triglycerides levels than TT homozygous (p = 0.046 and 0.049, respectively).

Conclusions

The allele C confers higher total cholesterol and triglycerides levels in dyslipidemic adults. The APOA5 − 1131T > C polymorphism is associated with dyslipidemia in male subjects.     

Cloning and expression analysis of novel Aux/IAA family genes in Gossypium hirsutum

The associations between polymorphisms of prostate stem cell antigen (PSCA-rs2294008C > T and -rs2976392G > A) and gastric cancer (GC) risk for Eastern Asians have been commonly studied, but the results were conflicting. The aim of the present study was to further assess the associations by the method of meta-analysis. The databases of Medline, Embase and CNKI (up to May 25th, 2011) were retrieved to identify eligible case-control studies. Odds ratio (OR) and 95% confidence interval (95%CI) were used to present the strength of the associations. In total, eight case-control studies in seven articles with 16792 individuals (9738 cases of GC and 7054 controls) were included in this meta-analysis. Through quantitative analyses, we found that T allele of rs2294008C > T and A allele of rs2976392G > A were significantly associated with increased GC risk [rs2294008C > T: OR (95%CI) = 1.31 (1.22-1.42), P_z-test < 0.001, P_{heterogeneity} = 0.166 for TT vs. C carriers; rs2976392G > A: OR (95%CI) = 1.36(1.24-1.50), P_z-test = 0.015, P_{heterogeneity} = 0.111 for AA vs. G carriers]. The results of subgroup analyses (according to histopathology, countries and sources of controls) indicated that T allele of rs2294008C > T and A allele rs2976392G > A were associated with increased risk of both intestinal- and diffuse-type GC, and associated with increased risk of GC for Chinese, Japanese, Koreans, PCC and HCC/PHCC. Furthermore, T allele of rs2294008C > T was also associated with increased risk of cardia and non-cardia GC, and associated with increased risk of GC for males and females. Besides those, this meta-analysis also indicated that the interactions between T allele of rs2294008C > T and A allele of rs2976392G > A was associated with increased risk of GC (A-T vs. G-T: OR = 1.16, 95%CI = 1.06-1.27, P_z-test = 0.001, P_{heterogeneity} = 0.835). Although modest limitations and potential bias cannot be eliminated, this meta-analysis suggests that PSCA -rs2294008C > T and -rs2976392G > A are potential factors of GC development for Eastern Asians, and future work may incorporate these findings and evaluate these variants as potential markers for screening and early diagnosis of GC.     

Assessment of clinical outcomes in breast cancer patients treated with taxanes: multi-analytical approach

Polymorphisms in genes encoding CYPs (Phase I) and ABCB1 (Phase III) enzymes may attribute to variability of efficacy of taxanes. The present study aims to find the influence of CYP and ABCB1 gene polymorphisms on taxanes based clinical outcomes. 132 breast cancer patients treated with taxanes based chemotherapy were genotyped for CYP3A4*1B, CYP3A5*3, CYP1B1*3, CYP2C8*3, ABCB1 1236C>T, 2677G>T/A and 3435C>T polymorphisms using PCR-RFLP. Associations of genetic variants with clinical outcomes in terms of response in 58 patients receiving neo-adjuvant chemotherapy (NACT), and chemo-toxicity in 132 patients were studied. Multifactor dimensionality reduction (MDR) analysis was performed to evaluate higher order gene–gene interactions with clinical outcomes. Pathological response to taxane based NACT was associated with GA genotype as well as A allele of CYP3A5*3 polymorphism (P_corr = 0.0465, P_corr = 0.0465). Similarly, association was found in dominant model of CYP3A5*3 polymorphism with responders (P_corr = 0.0465). Haplotype analysis further revealed A_CYP3A4–A_CYP3A5 haplotype to be significantly associated with responders (P_corr = 0.048). In assessing toxicity, significant association of variant (TT) genotype and T allele of ABCB1 2677G>T/A polymorphism, was found with ‘grade 1 or no leucopenia’ (P_corr = 0.0465, P_corr = 0.048). On evaluating higher order gene–gene interaction models by MDR analysis, CYP3A5*3; ABCB11236C>T and ABCB1 2677G>T/A; ABCB1 3435C>T and CYP1B1*3 showed significant association with treatment response, grade 2–4 anemia and dose delay/reduction due to neutropenia (P = 0.024, P = 0.004, P = 0.026), respectively. Multi-analytical approaches may provide a better assessment of pharmacogenetic based treatment outcomes in breast cancer patients treated with taxanes.     

EGF + 61A > G polymorphism and gastrointestinal cancer risk: A HuGE review and meta-analysis

Emerging evidences from preclinical and clinical studies have shown that epidermal growth factor (EGF) has some effectiveness against endogenously arising carcinogenesis. Functional + 61A > G polymorphism (rs4444903 A > G) in the promoter region of the EGF gene was observed to modulate EGF levels, thus affecting the susceptibility to gastrointestinal cancer; but individually published studies showed inconclusive results. The aim of this Human Genome Epidemiology (HuGE) review and meta-analysis was to derive a more precise estimation of the association between EGF + 61A > G polymorphism and gastrointestinal cancer risk. A literature search of Pubmed, Embase, Web of Science and Chinese BioMedical databases from inception through July 2012 was conducted. Twelve studies were assessed with a total of 2868 gastrointestinal cancer cases and 4278 healthy controls. When all the eligible studies were pooled into the meta-analysis, the results showed that the G allele and GG genotype of EGF + 61A > G polymorphism might increase the risk of gastrointestinal cancer. In the stratified analysis by cancer types, the G allele and GG genotype of EGF + 61A > G polymorphism showed displayed significant correlations with increased risk of esophageal cancer. We also found significant correlations between the G carrier (GG + AG) and GG genotype of EGF + 61A > G polymorphism and colorectal cancer risk. However, EGF + 61A > G polymorphism did not appear to have an influence on gastric cancer susceptibility. Results from the current meta-analysis indicate that EGF + 61A > G polymorphism might increase the risk of esophageal and colorectal cancers. Nevertheless, further studies are needed to determine whether genetic associations between EGF + 61A > G polymorphism and susceptibility to gastric cancer are significant.     

Associations of the PTEN − 9C>G polymorphism with insulin sensitivity and central obesity in Chinese

Background

Phosphatase and tensin homolog on chromosome 10 gene (PTEN) is known as a tumor-suppressor gene. Previous studies demonstrated that PTEN dysfunction affects the function of insulin. However, investigations of PTEN single nucleotide polymorphisms (SNPs) and IR-related disease associations are limited. The aim of the present study was to investigate whether its polymorphism could be involved in the risk of metabolic syndrome (MetS).

Methods

The genotype frequency of PTEN − 9C>G polymorphism was determined by using a Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry (MALDI-TOF MS) method in 530 subjects with MetS and 202 healthy control subjects of the Han Ethnic Chinese population in a case–control analysis.

Results

The PTEN − 9C>G polymorphism was not associated with MetS or its hyperglycemia, hypertension and hypertriglyceridemia components. In the control individuals aged < 60 years or ≥ 60 years, the CG genotype individuals had lower insulin sensitivity than CC individuals (P < 0.05). In the < 60-year-old MetS group and normal glucose tolerance (NGT) subgroup, the CG individuals had lower insulin sensitivity and higher waist circumference (WC) and waist-height-ratio (WHtR) than CC individuals (P < 0.05). Multiple linear regression analysis showed that the PTEN polymorphism (P = 0.001) contributed independently to 4.2% (adjusted R²) of insulin sensitivity variance (estimated by Matsuda ISI), while age (P = 0.004), gender (P = 0.000) and the PTEN polymorphism (P = 0.032) contributed independently to 5.6% (adjusted R²) of WHtR variance.

Conclusions

The CG genotype of PTEN − 9C>G polymorphism was not associated with MetS and some of its components as well. However, it may not only decrease insulin sensitivity in the healthy control and MetS in pre-elderly or NGT subjects, but may also increase the risk of central obesity among these MetS individuals.     

The ESR2 AluI 1730G>A (rs4986938) gene polymorphism is associated with fibrinogen plasma levels in postmenopausal women

The incidence of cardiovascular disease (CVD) and resultant morbidity and mortality are highly increased in postmenopausal women. Recent observations indicate the involvement of estrogen receptor beta in the pathogenesis of CVD, and the potential role of ESR2 gene polymorphisms as independent risk factors for CVD. We aimed to investigate the possible association between the ESR2 AluI 1730G>A gene polymorphism (rs4986938) with different CVD risk markers, such as body mass index (BMI), blood fibrinogen, glucose and insulin, homeostasis model assessment of insulin resistance and urinary F2-isoprostanes, in 89 postmenopausal women. Genotyping for ESR2 1730G>A polymorphism showed the higher prevalence of heterozygous GA1730 genotype than either wild-type GG1730 or homozygously mutated AA1730 genotype (50.6 vs 34.8 or 14.6%, respectively). Statistical analysis of between-group variability revealed that mean levels of the examined CVD risk markers, except BMI and fibrinogen, were within the normal range in all subjects grouped to different ESR2 1730G>A genotypes. Interestingly, only fibrinogen levels were statistically different in AA1730 carriers compared with other genotypes. The analysis of genotype relative risk showed a significant elevation of plasma fibrinogen in AA1730 carriers compared with GG + GA ones. The present data strongly indicate that genotyping for the ESR2 AluI 1730G>A gene variant should be included in a screening panel for assessment of cardiovascular risk in menopausal women.     

The Adiponectin variants contribute to the genetic background of type 2 diabetes in Turkish population

Adiponectin, an adipose tissue specific protein encoded by the Adiponectin gene, modulates insulin sensitivity and plays an important role in regulating energy homeostasis. Many studies have shown that single nucleotide polymorphisms (SNPs) in the Adiponectin gene are associated with low plasma Adiponectin levels, insulin resistance and an increased risk of type 2 diabetes mellitus. The aim of the present study was to evaluate the contribution of the Adiponectin gene polymorphisms in genetic background of type 2 diabetes in a Turkish population. In total, 169 unrelated and non-obese diabetic patients and 119 age- and BMI-matched non-diabetic individuals with no family history of diabetes were enrolled in this study. We detected a significant association between type 2 diabetes and two SNPs: SNP − 11391G > A, which is located in the promoter region of the Adiponectin gene, and SNP + 276G > T, which is found in intron 2 of the gene (P < 0.05). The silence SNP G15G (+ 45T > G) in exon 1 and SNP + 349A > G in intron 2 also showed a weak association with type 2 diabetes (P = 0.06 and P = 0.07, respectively), while SNPs − 3971A > G in intron 1 and Y111H, R112C and H241P in exon 3 showed no association (P > 0.05). In conclusion, these findings suggest that Adiponectin gene polymorphisms might be effective on susceptibility for type 2 diabetes development which emerged from the interactions between multiple genes, variants and environmental factors.     

COX-2 polymorphisms − 765G→C and − 1195A→G and hepatocellular carcinoma risk

Cyclooxygenase-2 (COX-2) is overexpressed in hepatocellular carcinoma (HCC) and considered to play a role in hepatic carcinogenesis. Our aim was to examine the associations between polymorphisms in COX-2 − 765G→C and − 1195A→G and risk of HCC. We conducted a case–control study including 120 patients with HCC and 130 age- and gender-matched controls. Genotypes of the COX-2 polymorphisms − 765G→C and − 1195A→G were determined by polymerase chain reaction-based restriction fragment length polymorphism. No significant difference was observed in the genotype distribution of the − 765G→C polymorphism between patients and controls. The − 1195AA genotype was associated with an increased risk of developing HCC (OR, 2.5; 95%CI, 1.18–5.37). The A allele was present significantly more often in HCC patients (OR 1.5; 95%CI, 1.05–2.14). In conclusion, our results demonstrated that the − 1195AA genotype and A allele have an important role in HCC risk in Egyptian patients.     

Association between the − 786T>C 1polymorphism in the promoter region of endothelial nitric oxide synthase (eNOS) and risk of coronary artery disease: A systematic review and meta-analysis

Background

A variety of studies have evaluated the association between the − 786T>C polymorphism in the promoter region of endothelial nitric oxide synthase (eNOS) and risk of coronary artery disease (CAD). However, the results remain conflicting. To better understand the role of eNOS − 786T>C polymorphism in CAD risk, we conducted a comprehensive systematic review and meta-analysis.

Methods

Case–control, cohort or cross-sectional studies evaluating the association between eNOS − 786T>C polymorphism and CAD risk were searched in electronic databases of PubMed, ISI Web of Knowledge, Medline, Embase and Google Scholar Search (up to January 2013). Overall and subgroup analyses were performed. Odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the association between eNOS − 786T>C polymorphism and CAD risk. Statistical analysis was performed with Review Manager 5.0 and STATA12.0.

Results

Twenty-four studies were analyzed between 6192 CAD cases and 9281 healthy controls. The combined results of overall analysis showed significant positive associations between CAD risk and eNOS − 786T>C polymorphism in dominant model (OR = 1.45, 95% CI = 1.27–1.65), recessive model (OR = 1.37, 95% CI = 1.20–1.56), homozygote comparison (OR = 1.64, 95% CI = 1.31–2.04), heterozygote comparison (TC vs. TT, OR = 1.39, 95% CI = 1.23–1.57; CC vs. TC, OR = 1.20, 95% CI = 1.04–1.37) and allele comparison (OR = 1.35, 95% CI = 1.21–1.50). On subgroup analysis based on the ethnicity of population (Caucasians, Asians and others), significant differences were found in all genetic models for Caucasians, similar associations existed in Asians except heterozygote comparison (CC vs. TC). However, the associations were only found in dominant model, heterozygote comparison (TC vs. TT) and allele comparison for the populations named others.

Conclusions

Our investigations demonstrate the significant associations between eNOS − 786C>T polymorphism and CAD risk, and this polymorphism might become an early marker for the risk evaluation of CAD.     

Apolipoprotein A5 T-1131C variant and risk for metabolic syndrome in obese adolescents

Background

Apolipoprotein A5 (APOA5) gene variants are associated with increased plasma triglycerides, a risk factor for metabolic syndrome (MS). The goal of the current study was the investigation of the distribution of T-1131C variant among obese adolescents with MS compared with healthy controls.

Subjects and methods

The study included 150 obese adolescents (75 males and 75 females) with MS and 204 age and sex matched normal healthy controls (100 males and 104 females). The mean age of the patients was 15.47 ± 2.54 years, ranged from 17 to 20 years. They were genotyped by polymerase chain reaction–restriction fragment length polymorphism for the mutation (T-1131C).

Results

The blood pressure, triglyceride and HOMA-R levels were significantly higher and HDL-C levels were significantly lower in carrier (TC + CC) compared to non-carrier (TT) MS patients. There was accumulation of − 1131C allele frequency in the MS group (31.33% vs. control group 11.76%), p < 0.001. The genotypes were in Hardy–Weinberg equilibrium both in the patients with metabolic syndrome and in the control subjects. Results of analysis of multiple regression models showed that the ApoA5 − 1131C carriers showed an increased incidence of MS (OR = 1.73, 95% CI: 1.41–2.11).

Conclusions

The present study suggests that the 1131T>C polymorphism is a risk factor for the development of metabolic syndrome in obese adolescents.