A common variant in the adiponectin gene and polycystic ovary syndrome risk

In this study, we explored whether polymorphisms in insulin receptor (INSR), adiponectin (ADIPOQ), parathyroid hormone (PTH), and vitamin D receptor (VDR) genes are associated with polycystic ovary syndrome (PCOS). A total of 362 subjects, including 181 women with PCOS and 181 controls were enrolled in this case-control study. Two SNPs (rs2059806 and rs1799817) in the INSR gene, two SNPs (rs2241766 and rs1501299) in the ADIPOQ gene, one SNP (rs6256) in the PTH gene, and one SNP (rs757343) in the VDR gene were analyzed using PCR-RFLP method. We observed no significant difference in genotype and allele frequencies between the women with PCOS and controls for the rs2059806, rs1799817, rs1501299, rs6256, and rs757343 polymorphisms either before or after adjustment for confounding factors including age and BMI. However, the ADIPOQ rs2241766 “TT” genotype compared with “TG and GG” genotypes was associated with a 1.93-fold increased risk for PCOS (P = 0.006, OR = 1.93, 95% CI = 1.20–3.11), and the differences remained significant after adjustment for age and BMI (P = 0.039, OR = 1.72, 95% CI = 1.03–2.86). Furthermore, the ADIPOQ rs2241766 “T” allele was significantly overrepresented in women with PCOS than controls (P = 0.006; OR = 1.80, 95% CI = 1.18–2.70), and the difference remained significant after Bonferroni correction. Our findings suggest that the ADIPOQ rs2241766 “TT” genotype is a marker of increased PCOS susceptibility. This study also indicates for the first time that there are no significant association between INSR rs2059806, PTH rs6256, and VDR rs757343 gene polymorphisms and PCOS risk. However, these data remain to be confirmed in larger studies and in other populations.     

Association of Genetic Variants in the Adiponectin Gene with Metabolic Syndrome: A Case-Control Study and a Systematic Meta-Analysis in the Chinese Population

Background

The prevalence of metabolic syndrome has been rising worldwide, including in China, but knowledge on specific genetic determinants of metabolic syndrome is very limited. A number of studies have reported that polymorphisms in the ADIPOQ gene are associated with metabolic syndrome in Chinese Han populations. However, data is still conflicting. The objective of this study was to examine the associations of the adiponectin genetic variants with metabolic syndrome by a case-control study and meta-analyses in Chinese.

Methods

We first investigated the association of ADIPOQ rs2241766 (+45T>G in exon 2), rs266729 (−11377C>G in promoter) and rs1501299 (+276G>T in intron 2) polymorphisms with metabolic syndrome in a Hubei Han Chinese population with 322 metabolic syndrome patients and 161 normal controls recruited from the Yichang, Hubei. Then we comprehensively reviewed the association between ADIPOQ rs2241766/rs266729/rs1501299 and metabolic syndrome in the Chinese populations via a meta-analysis. The strength of association was assessed by odds ratios (ORs) with 95% confidence intervals (CI).

Results

The G allele frequency of rs2241766 in metabolic syndrome patients was significantly higher than those of controls group (29.8% vs 23.3%, OR = 1.40, P = 0.033). The logistic regression analysis adjusted by gender and age showed a nominally significant association for rs2241766 GG+GT genotype (P = 0.065, OR = 1.55) and rs1501299 GG genotype in recessive model (OR = 1.54, P = 0.066). However, no association was observed for rs266729 in our sample. We identified thirteen studies for rs2241766 (2,684 metabolic syndrome patients and 2,864 controls), three studies for rs266729, and eleven studies for rs1501299 (2,889 metabolic syndrome patients and 3,304 controls) in Chinese. Meta-analysis indicated significant associations for the rs2241766 G allele (OR = 1.14, 95%CI = 1.05–1.24, P = 0.003), rs266729 GG+GT genotypes (OR = 0.80, 95%CI = 0.68–0.92, P = 0.003) and rs1501299 GG+TG genotypes (OR = 1.42, 95%CI 1.16–1.75, P = 0.001).

Conclusions

Our results demonstrated ADIPOQ as a pleiotropic locus for metabolic syndrome and its components in the Han Chinese population.     

The role of adiponectin (ADIPOQ) gene polymorphisms in the susceptibility and prognosis of non-small cell lung cancer

To study the role of the adiponectin (ADIPOQ) gene single-nucleotide polymorphism (SNP) in the susceptibility and prognosis for non-small cell lung cancer (NSCLC), we recruited 344 patients with NSCLC, of which 141 had undergone surgical resection and post-surgery follow up.?For controls, there were 264 healthy volunteers for the control group, matched in age and sex with the NSCLC patients. Genotyping of SNPs in the ADIPOQ gene, namely, rs266729 (11365C>G); rs822395 (4034A>C); rs822396 (3964A>G); rs2241766 (+45T>G) were performed. Of all SNPs in the ADIPOQ gene, only the TT genotype and T allele frequency of the rs2241766 were more prevalent in NSCLC subjects than in controls. The TT genotype of rs2241766 was significantly associated with susceptibility to NSCLC before and after adjustment for age, sex, body mass index, and smoking status. In the survival analyses of subjects receiving surgical resection, only the SNPs of rs2241766 were significantly related to overall survival of NSCLC. Our results suggest that the SNP rs2241766 of the ADIPOQ gene may determine both susceptibility to NSCLC, and the prognosis for those who underwent surgical treatment.     

Relationship between Adiponectin Gene Polymorphisms and Late-Onset Alzheimer’s Disease

In recent years, researchers have found that adiponectin (ANP) plays an important role in the pathogenesis of Alzheimer''s disease (AD), and low serum concentrations of ANP are associated with AD. Higher plasma ANP level have a protective effect against the development of cognitive decline, suggesting that ANP may affect AD onset. Meanwhile, accumulating evidence supports the crucial role of ANP in the pathogenesis of AD. To study the relationship between ANP gene polymorphisms (rs266729, -11377C>G and rs1501299, G276T) and late-onset AD (LOAD), we carried out a case-control study that included 201 LOAD patients and 257 healthy control subjects. Statistically significant differences were detected in the genotype and allelotype frequency distributions of rs266729 and rs1501299 between the LOAD group and the control group, with a noticeable increase in the G and T allelotype frequency distributions in the LOAD group (P < 0.05). Logistic regression analysis using recessive model and additive model revealed that the rs266729 GG and rs1501299 TT genotypes are associated with a greater risk of LOAD. Haplotype analysis identified four haplotypes: CG, CT, GG, and GT. The frequencies of the CT and GG haplotypes were not significantly different (P > 0.05) between the LOAD group and control group, whereas the CG and GT haplotypes were significantly different (P < 0.05), suggesting a negative correlation between the CG haplotype and LOAD onset (OR = 0.74, 95% CI = 0.57–0.96, P = 0.022), and a positive correlation between the GT haplotype and LOAD onset (OR = 2.29, 95% CI = 1.42–3.68, P = 0.005). Therefore, we speculated that the rs266729 and rs1501299 of ANP gene polymorphisms and the GT and CG haplotypes were associated with LOAD.     

Common polymorphisms (rs2241766 and rs1501299) in the ADIPOQ gene are not associated with hypertension susceptibility among the Chinese

The ADIPOQ gene has been implicated in the etiology of hypertension. However, the results have been inconsistent. In this study, a meta-analysis was performed to assess the associations of ADIPOQ polymorphisms with hypertension risk among the Chinese. Published literature from PubMed, CNKI and Wanfang Data were retrieved. Pooled odds ratio (OR) with 95 % confidence interval (CI) was calculated using fixed- or random-effects model. Six studies (1,812 cases and 2,631 controls) for rs2241766 polymorphism and four studies (1,449 cases and 2,175 controls) for rs1501299 polymorphism were identified. A marginally significant association was observed for rs2241766 polymorphism under recessive genetic model (GG vs. GT+TT: OR = 1.22, 95 % CI 1.01-1.48) and for rs1501299 polymorphism under heterogeneous co-dominant model (TG vs. GG: OR = 0.86, 95 % CI 0.75-0.99) and dominant model (TT+TG vs. GG: OR = 0.85, 95 % CI 0.74-0.98). In addition, under other genetic models, there was no significant association for rs2241766 polymorphism (GG vs. TT: OR = 1.20, 95 % CI 0.98-1.48; GT vs. TT: OR = 0.97, 95 % CI 0.85-1.10; GG+GT vs. TT: OR = 1.01, 95 % CI 0.90-1.15) and for rs1501299 polymorphism (TT vs. GG: OR = 0.82, 95 % CI 0.62-1.08; TT vs. TG+GG: OR = 0.87, 95 % CI 0.66-1.14). However, the associations above were not robust by sensitivity analysis. The present meta-analysis indicated the limited evidence of the significant associations between ADIPOQ gene polymorphisms and hypertension susceptibility among the Chinese.     

Vascular endothelial growth factor (VEGF) +405 C/G polymorphism is associated with essential hypertension in a population from Tehran of Iran

Vascular endothelial growth factor (VEGF) has long been recognized as a hypotensive mediator. Little is known regarding the contribution of polymorphisms in VEGF gene to essential hypertension (EH), however. We aimed to investigate the association between +405 VEGF C/G single nucleotide polymorphism (SNP) and occurrence of EH in a sample of patients with diabetes. A study population of 474 subjects with diabetes of which 45.6% (216) had EH was enrolled in this study. Interviews and physical examinations were performed in a clinical setting. Subjects were matched in baseline anthropometric and biochemical characteristics except for total cholesterol. Genotyping of +405 VEGF C/G (rs2010963) SNP was carried out using polymerase chain reaction–restriction fragment length polymorphism. The allelic distribution of the sample did not violate Hardy–Weinberg equilibrium. Subjects with EH had a higher frequency of G allele (P = 0.005). Additionally, those with EH had a significantly higher frequency of GG genotype (P = 0.015). In multivariate logistic regression models controlling for possible confounders, having GG against CC genotype was associated with an odds ratio of 2.51 (95% CI: 1.44–4.38; P = 0.001). Moreover, presence of each G allele was linked to a 1.58-fold increase in risk of having EH (95% CI: 1.200–2.086; P = 0.001). In conclusion, +405 VEGF C/G SNP is associated with EH in patients with diabetes, suggesting presence of G allele and GG or CG genotype confer susceptibility towards EH.     

Association of 1347 G/A cytochrome P450 4F2 (CYP4F2) gene variant with hypertension and stroke

Genetic variants of cytochrome P450 4F2 (CYP4F2) gene have been suggested to be risk factors for hypertension, cardiovascular diseases and stroke. In the present case–control study we investigated the association of 1347 G/A polymorphism (rs2108622) in the 11th exon region of CYP4F2 gene with hypertension, ischemic stroke and stroke subtypes classified according to TOAST (Trial of Org 10172 in Acute Stroke Treatment) classification. Five hundred and seven stroke patients (hypertensives: normotensives = 279:228) and four hundred and eighty seven, age and sex matched controls (males: females = 356:131) (hypertensives: normotensives = 148:339) were involved in the study. The genotypes were determined by PCR-RFLP technique. Genotypes were confirmed by subjecting the PCR products to sequencing. Significant difference was observed in the genotypic distribution and allelic frequency between the stroke patients and healthy controls. AA genotype and A allele associated significantly with stroke and hypertension [P = 0.009; OR = 1.59 (95% CI = 1.119–2.283) and P = 0.010; OR = 1.26 (95% CI = 1.056–1.502); P = 0.01; OR = 1.58 (95% CI = 1.11–2.272) and P = 0.010; OR = 1.25(95% CI = 1.054–1.504) respectively]. A stepwise logistic regression analysis confirmed these findings. To establish that this polymorphism is associated with stroke independent of hypertension; we compared stroke patients without hypertension with normotensive controls. Significant difference was observed in genotypic distribution and allelic frequency between the two groups (P = 0.001 and 0.002 respectively). Evaluating the association of this polymorphism with stroke subtypes we found significant associations with cardioembolic stroke (P < 0.001). In conclusion our study suggests that 1347A allele of CYP4F2 gene is an important risk factor for hypertension and ischemic stroke.     

The roles of ADIPOQ genetic variations in cancer risk: evidence from published studies

Adiponectin produced by adipose tissue, which is involved in complex diseases related to obesity, such as cancer. Genetic variations in ADIPOQ are thought to influence the activity of adiponectin, thus relating to cancer occurrence. However, epidemiological results were inconsistent. To examine this controversy, we assessed reported studies of association between ADIPOQ polymorphisms and cancer risk. Relevant studies were selected by PUBMED, EMBASE update to January 12th, 2012. According to the acceptance and exclusion criteria, 15 studies involved three polymorphisms (rs266729, rs2241766, rs1501299) of ADIPOQ were included. Summary odds ratio (ORs) and 95 % confidence intervals (CIs) were calculated using random-effect or fixed-effect models based on the heterogeneity of included studies. A total of 15 case–control studies related rs266729 (5,615 cases and 6,425 controls), rs2241766 (5,318 cases and 6,118 controls) and rs1501299 (3,751 cases and 5,104 controls) were included to analyze the ADIPOQ polymorphisms and cancer risk. For rs1501299, T allele was associated with decreased cancer risk. In addition, cancer type subgroup analysis revealed T allele was associated with decreased colorectal and prostate cancer risk. Ethnicity subgroup analysis observed a decreased risk in both Asian and Caucasian descendents. As to rs2241766, a borderline decreased cancer risk was observed. This meta-analysis indicated T allele of rs1501299 was an obvious protection factor for cancer risk, and G allele of rs2241766 was a potential protection factor for cancer risk, especially in Caucasian descendents. Further studies should be performed to clarify the roles of ADIPOQ polymorphisms in the cancer risk.     

ADIPOQ gene polymorphisms and cancer risk: A meta-analysis

The results of studies investigating the association between ADIPOQ gene polymorphisms and risk of cancer have been inconsistent and often contradictory. The present meta-analysis was conducted in order to overcome the limitations of any individual study and to provide a more precise overall effect estimate. Relevant studies were identified by searching PubMed and Embase for articles published through May 2012. The strength of the relationship between the ADIPOQ gene and risk of cancer was assessed using odds ratios (ORs). Either a fixed-effects or a random-effects model was used to calculate the overall risk estimates. Fifteen studies were included and five SNPs were considered. A significant association was found between SNP rs2241766 and risk of cancer in the recessive genetic model (OR: 0.768, 95% CI: [0.626, 0.942], P = 0.011); a significant relationship was also found between SNP rs1501299 and risk of cancer in both an allele contrast (OR: 0.141, 95%CI: [0.113, 0.176], P < 0.001) and the dominant genetic model (OR: 0.904, 95%CI: [0.830, 0.985], P = 0.021); no association was found with the rs266729, rs822395, or rs822396 SNPs. Adjusted ORs were also considered, but no statistically significant association was found in homozygote contrasts for any of the five SNPs after adjustment. Our results suggest that two polymorphisms, SNP rs2241766 and SNP rs1501299, of the ADIPOQ gene may be associated with reduced risk of cancer. However, the overall strength of association is mild to moderate, and additional well-designed studies are needed to confirm the present conclusion.     

A novel association of a polymorphism in the first intron of adiponectin gene with type 2 diabetes, obesity and hypoadiponectinemia in Asian Indians

Adiponectin is an adipose tissue specific protein that is decreased in subjects with obesity and type 2 diabetes. The objective of the present study was to examine whether variants in the regulatory regions of the adiponectin gene contribute to type 2 diabetes in Asian Indians. The study comprised of 2,000 normal glucose tolerant (NGT) and 2,000 type 2 diabetic, unrelated subjects randomly selected from the Chennai Urban Rural Epidemiology Study (CURES), in southern India. Fasting serum adiponectin levels were measured by radioimmunoassay. We identified two proximal promoter SNPs (−11377C→G and −11282T→C), one intronic SNP (+10211T→G) and one exonic SNP (+45T→G) by SSCP and direct sequencing in a pilot study (n = 500). The +10211T→G SNP alone was genotyped using PCR-RFLP in 4,000 study subjects. Logistic regression analysis revealed that subjects with TG genotype of +10211T→G had significantly higher risk for diabetes compared to TT genotype [Odds ratio 1.28; 95% Confidence Interval (CI) 1.07–1.54; P = 0.008]. However, no association with diabetes was observed with GG genotype (P = 0.22). Stratification of the study subjects based on BMI showed that the odds ratio for obesity for the TG genotype was 1.53 (95%CI 1.3–1.8; P < 10⁻⁷) and that for GG genotype, 2.10 (95% CI 1.3–3.3; P = 0.002). Among NGT subjects, the mean serum adiponectin levels were significantly lower among the GG (P = 0.007) and TG (P = 0.001) genotypes compared to TT genotype. Among Asian Indians there is an association of +10211T→G polymorphism in the first intron of the adiponectin gene with type 2 diabetes, obesity and hypoadiponectinemia.     

Association between TNF-α polymorphisms and cervical cancer risk: a meta-analysis

Tumor necrosis factor alpha (TNF-α) is a vital cytokine involved in inflammation, immunity, and cellular organization. The TNFA-308G/A (rs1800629) and -238G/A (rs361525) polymorphisms are two widely investigated variants for their associations with risk of cervical cancer, but the results are conflicting. Here, we performed a meta-analysis to pool the data and evaluate the between-studies heterogeneity. All the case–control studies published from January 1989 to October 2010 on the association between the two polymorphisms of TNFA and cervical cancer risk were identified by searching the electronic literature Medline. The cervical cancer risk associated with the two polymorphisms of TNFA gene was estimated for each study by OR together with its 95% CI, respectively, by using the Review Manager 4.2 software. It was showed that the variant homozygote -308AA was associated with a significantly increased risk of cervical cancer (AA vs. GG: OR = 1.41, 95% CI = 1.03–1.92, P = 0.033; AA vs. GA/GG: OR = 1.39, 95% CI = 1.02–1.90, P = 0.036), and the effect was more evident among Asians (AA vs. GA/GG: OR = 3.67, 95% CI = 1.25–10.81, P = 0.018). We also found that the variant genotypes -238GA/AA was associated with a significantly decreased risk of cervical cancer (GA/AA vs. GG: OR = 0.55, 95% CI = 0.41–0.74, P < 0.001). The results suggested that TNFA-308G/A and -238G/A may contribute to cervical cancer susceptibility.     

Meta-analysis of TYK2 gene polymorphisms association with susceptibility to autoimmune and inflammatory diseases

The aim of our meta-analysis was to quantitatively summarize the association of TYK2 gene polymorphisms with autoimmune and inflammatory diseases. 11 studies that included data from 21497 cases and 22647 controls were identified. OR was used as a measure of the effect of the association in a fixed/random effect model. Meta-analysis was performed for six TYK2 gene polymorphisms (rs34536443, rs2304256, rs280523, rs280519, rs12720270 and rs12720356). Significant association was found in rs34536443 (C versus G: OR = 0.76, 95% CI = 0.69–0.84, P < 0.00001; GC + CC versus GG: OR = 0.78, 95% CI = 0.68–0.90, P = 0.0005; CC versus GG + GC: OR = 0.76, 95% CI = 0.28–2.05, P = 0.58; CC versus GG: OR = 0.74, 95% CI = 0.27–2.02, P = 0.56; GC versus GG: OR = 0.78, 95% CI = 0.68–0.90, P = 0.0006) and rs2304256 (A versus C: OR = 0.78, 95% CI = 0.70–0.87, P < 0.0001; CA + AA versus CC: OR = 0.69, 95% CI = 0.59–0.81, P < 0.0001; AA versus CC + CA: OR = 0.75, 95% CI = 0.66–1.00, P = 0.05; AA versus CC: OR = 0.64, 95% CI = 0.47–0.86, P = 0.003; CA versus CC: OR = 0.70, 95% CI = 0.60–0.83, P < 0.0001) in TYK2 gene, but not for the other polymorphisms (rs280523, rs280519, rs12720270, and rs12720356). This meta-analysis demonstrates that autoimmune and inflammatory diseases is associated with TYK2 gene rs34536443 and rs2304256 polymorphisms, but not rs280523, rs280519, rs12720270 and rs12720356.     

The Ku70 ?1310C/G promoter polymorphism is associated with breast cancer susceptibility in Chinese Han population

Ku70 plays an important role in the DSBR (DNA double-strand breaks repair) and maintenance of genomic integrity. Genetic variations within human Ku70 have been demonstrated to be associated with increased risk of several types of cancers. In this hospital-based case–control study, we aimed to investigate whether a single nucleotide polymorphism (SNP) in the promoter region (rs2267437) of Ku70 gene is associated with susceptibility to breast cancer in Chinese Han population. A total of 293 patients with breast cancer and 301 age-matched healthy controls were enrolled in this study. The Ku70 −1310C/G polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP) analysis. A significant difference in genotype distribution and allele frequency was observed between patients and controls. The CG or GG carries were at higher risk of breast cancer compared with the CC homozygotes (OR = 1.43, 95% CI = 1.02–2.00, P = 0.038 and OR = 3.53, 95% CI = 1.60–7.80, P = 0.002, respectively). Further stratification analysis revealed that G allele was associated with an increased risk of breast cancer among premenopausal women (OR = 1.68, 95% CI = 1.21–2.33, P = 0.002), but not in postmenopausal women (OR = 1.33, 5% CI = 0.85–2.10, P = 0.216). Our study suggests that the Ku70 −1310C/G promoter polymorphism may be a susceptibility factor for breast cancer in Chinese Han population.     

CXCL12 G801A polymorphism and breast cancer risk: a meta-analysis

The G801A polymorphism in the CXCL12 gene has been implicated in breast cancer risk. However, the published findings are inconsistent. We therefore performed a meta-analysis to investigate this relationship. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association. The pooled ORs were performed for codominant model, dominant model, and recessive model, respectively. Five published case–control studies, including 1,058 breast cancer cases and 1,023 controls were identified. No study had a deviation from the Hardy–Weinberg equilibrium (HWE) in controls. We found that the CXCL12 G801A (rs1801157) polymorphism was associated with a significantly increased risk of breast cancer risk when all studies were pooled into the meta-analysis (codomiant model: AA versus GG, OR = 1.64, 95% CI = 1.16–2.33; GA versus GG, OR = 1.42, 95% CI = 1.18–1.71; dominant model: AA/GA versus GG, OR = 1.44, 95% CI = 1.21–1.72). Furthermore, Egger’s test did not show any evidence of publication bias (P > 0.05 for the dominant model). In conclusion, the results suggest that the CXCL12 G801A polymorphism may be a low-penetrant risk factor for developing breast cancer.     

Association between ATM polymorphisms and cancer risk: a meta-analysis

To date, epidemiological studies have assessed the association between Ataxia-telangiectasia mutated (ATM) gene polymorphisms and cancer risk, including lung cancer, breast cancer, glioma and pancreatic cancer. However, the results of these studies remain controversial. We aimed to examine the associations between two SNPs (rs664143 and rs664677) and cancer risk by conducting a meta-analysis of case–control studies. A total of 12 publications were included in this meta-analysis, 8 for rs664143 and 7 for rs664677. Overall, rs664143 heterozygote carriers turned out to be associated with cancer risk (OR = 1.18, 95% CI 1.02–1.36). In the subgroup analysis by cancer type, we observed that the ATM rs664143 polymorphism was significantly associated with lung cancer risk (GA vs. GG: OR = 1.48, 95% CI 1.18–1.85, AA vs. GG: OR = 1.51, 95% CI 1.18–1.93) and rs664677 polymorphism was associated with decreased lung cancr risk and increased breast cancer risk (for lung cancer: TC vs. TT: OR = 0.76, 95% CI 0.62–0.92, CC vs. TT: OR = 0.80, 95% CI 0.64–0.99 and for breast cancer: TC vs. TT: OR = 1.42, 95% CI 1.17–1.73, CC vs. TT: OR = 1.51, 95% CI 1.21–1.87). In the subgroup analysis by region, we also observed that individuals with ATM rs664143 GA or AA genotype had an obvious increased cancer risk among Asian people (GA vs. GG: OR = 1.40, 95% CI 1.20–1.63, AA vs. GG: OR = 1.37, 95% CI 1.16–1.62). In conclusion, ATM rs664143 polymorphism was associated with cancer susceptibility. ATM rs664143 polymorphism was significantly associated with lung cancer risk. ATM rs664677 polymorphism was associated with decreased lung cancer risk as well as increased breast cancer risk.     

XPA A23G polymorphism and lung cancer risk: a meta-analysis

Case–control studies on the association between XPA A23G and lung cancer have provided either controversial or inconclusive results. To clarify the effect of XPA A23G on the risk of lung cancer, a meta-analysis of all case–control observational studies was performed. Pooled odds ratios (ORs) for various polymorphisms were estimated using random and fixed effects models. The Q-statistic was used to evaluate the homogeneity, and Egger and Begg tests were used to assess publication bias. For the homozygote GG and G allele carriers (GA + GG), the pooled ORs were 1.24 (95% CI 1.05–1.46; P = 0.27 for heterogeneity) and 1.30 (95% CI 1.13–1.51; P = 0.45 for heterogeneity) compared to the homozygous genotype (AA). In the stratified analysis by ethnicity, the ORs of the G allele carriers and the homozygote GG were 1.28 (95% CI 1.10–1.49; P = 0.07 for heterogeneity) and 1.42 (95% CI 1.04–1.93; P = 0.39 for heterogeneity) among non-Caucasians. No significant associations were found in the Caucasian population in any of the genetic models. When studies that were not in Hardy–Weinberg equilibrium (HWE) were corrected, the pattern of the results remained the same. Our results indicated a significantly decreased risk of lung cancer in non-Caucasians with the G allele.     

Current evidence on the relationship between CYP1B1 polymorphisms and lung cancer risk: a meta-analysis

The association between single-nucleotide polymorphisms (SNPs) of the CYP1B1 gene and lung cancer risk is still ambiguous. In this meta analysis, we assessed 10 case–control studies included 7,067 cases and 9,374 controls of the association between CYP1B1 SNPs of Leu432Val (rs1056836, 432C>G), Asn453Ser (rs1800440, 453A>G), Ala119Ser (rs1056827, 119G>T), Arg48Gly (rs10012, 48C>G) and the risk of lung cancer. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the strength of association between the polymorphism and lung cancer risk under codominant model, dominant model and additive model respectively. Although there were limitations, this meta analysis indicated that individuals with 432GG genotype had a 39.7% higher risk of having lung cancer than those with the 432CC genotype, and individuals with the 432G allele had a 26.3% increased risk as well. An increased risk of lung cancer of 2.13 fold was observed in individuals with 119TT genotype. For Arg48Gly, individuals with 48GG genotype had a significantly increased risk of lung cancer compared with individuals with 48CC (OR 3.859; 95% CI 2.536–5.87). Elevated risk of lung cancer were observed in dominant model (OR 2.115; 95% CI 1.653–2.705) as well. The risk of lung cancer was elevated as the frequency of G allele increased in additive model (P = 0.000). For individuals with the polymorphism at codon 453, no evidence of such association was observed. Furthermore, a possible association between the CYP1B1 polymorphism at codon 432 and the lung cancer could be detected in individuals of Caucasian origin, while a negative association was suggested in Asians and African-Americans. An increased lung cancer risk was also found in women with polymorphism at codon 453. These results are supportive for the hypothesis that the CYP1B1 432GG, 119TT and 48GG genotypes are low-penetrance risk factors for developing lung cancer, and further studies are needed to validate these associations.     

Association study of the single nucleotide polymorphisms in adiponectin-associated genes with type 2 diabetes in Han Chinese

Single-nucleotide polymorphisms （SNPs） of ADIPOQ, ADIPOR1, and ADIPOR2 have been associated with type 2 diabetes mellitus （T2DM）, but there are many conflicting results especially in Chinese populations. To investigate the contribution of the adiponectin genes and their receptors to T2DM, a case-control study was performed and 11 SNPs ofADIPOQ, ADIPOR1, and ADIPOR2 were genotyped in 985 T2DM and 1,050 control subjects, rs 16861194 （-11426 A〉G） in the putative promoter of ADIPOQ was associated with T2DM （P = 0.007; OR = 1.29, 95% CI 1.08-1.55）. None of the other 10 SNPs were associated with T2DM in this study, although rs2241766 and rs1501299 were reported to be associated with T2DM in previous Chinese studies. There was also no significant difference found from the ADIPOQ haplotype analysis, which contains rs 16861194. In addition, we also assessed potential gene-gene interactions in three genes and no interactions were found. In conclusion, our results supported the ADIPOQ gene as a possible risk factor for type 2 diabetes in Han Chinese population.     

IL-10R1 S138G loss-of-function polymorphism is associated with extrapulmonary tuberculosis risk development in Tunisia

There is considerable evidence that host genetic factors are important in determining susceptibility to mycobacterial infections. More recently, functional genetic mutations affecting IL-10 receptor 1 (IL-10R1) were described. In this study, we investigated the relationship of IL-10R1 S138G loss-of-function polymorphism (A536G: rs3135932) with susceptibility to active tuberculosis (TB) in Tunisian patients. A total of 168 patients with pulmonary TB, 55 with extrapulmonary TB, and 150 control subjects were studied. Genomic DNA samples were extracted from leukocytes and used to investigate S138G polymorphism in IL-10R1 gene by multiplex allele-specific polymerase chain reaction. Associations between G allele [odds ratio OR = 5.01; 95% confidence intervals CI = 2.58–9.77; P = 10⁻⁷], GG genotypes [OR=9.06; 95% CI (1.58–67.33); correcting P-values using the Bonferroni method for multiple tests Pc=0.015] and AG genotype [OR=3.75; 95% CI (1.62–8.7); Pc=0.0012] with the risk development of active extrapulmonary TB were found. In contrast, the AA genotype was found to be associated with resistance to extrapulmonary TB [OR=0.19; 95% CI (0.09–0.42); Pc=6.10⁻⁶]. No association was found between S138G SNP and pulmonary TB. In conclusion, our study suggested the possible role of IL-10R1 S138G loss-of-function polymorphism in extrapulmonary TB susceptibility-resistance in Tunisia.     

Association analysis of p16 (CDKN2A) and RB1 polymorphisms with susceptibility to cervical cancer in Indian population

The potent tumor suppressors P16 and RB1 are the key regulators of cell cycle machinery in eukaryotes. Polymorphisms in these genes play an important role in the outcome of various diseases including cancer. In the present study, we evaluated the association of p16 and RB1 polymorphisms with cervical cancer susceptibility in Indian population. We screened 150 histologically confirmed cervical cancer cases along with equal number of healthy controls with normal cervical cytology. PCR-RFLP method was employed for genotyping of SNPs in p16 C540G (rs11515), C580T (rs3088440) in the 3′-UTR of exon 3 and RB1 A153104G (rs4151580) located in the intron 18 and confirmed by direct sequencing. Both patients and controls were screened for HPV infection. In this case–control study 84.67% (127/150) of cases were found to be positive for HPV DNA sequence. Women carrying p16 C540G carrier genotypes 540 (CG/GG) may have protective effect for the development of cervical cancer (P = 0.0001, OR = 0.31, 95% CI = 0.17–0.56). And SNP at C580T of p16 gene was found to be negatively associated with the risk of cervical cancer (P = 0.0004, OR = 0.04, 95% CI = 0.002–0.63). p16 (540C/580T) has emerged as a major risk haplotype (P = 0.033, OR = 1.47, 95% CI = 1.05–2.07) whereas p16 (540G/580T) as a chief protective haplotype (P = 0.014, OR = 0.39, 95% CI = 0.18–0.83) for the development of cervical cancer among Indian women. Contrary to this, SNP at A153104G of RB1 gene showed statistically significant association (P = 0.035, OR = 1.69, 95% CI = 1.06–2.68) with increased susceptibility for the development of cervical cancer. Our results suggest that single nucleotide polymorphisms in p16, RB1 genes may affect the susceptibility to cervical cancer collectively.