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.     

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.     

Effects of <Emphasis Type="Italic">ADIPOQ</Emphasis> polymorphisms on PCOS risk: a meta-analysis

Background

Whether adiponectin (ADIPOQ) polymorphisms are associated with the risk of polycystic ovary syndrome (PCOS) remain controversial. Therefore, we performed this study to better explore correlations between ADIPOQ polymorphisms and PCOS risk.

Methods

Literature retrieve was conducted in PubMed, Medline and Embase. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated.

Results

Eighteen studies were enrolled for analyses. Pooled overall analyses showed that rs1501299 polymorphism was significantly associated with PCOS risk (recessive model: p?=?0.02, OR?=?0.77, 95%CI 0.62–0.95; allele model: p?=?0.001, OR?=?1.15, 95%CI 1.06–1.26). Further subgroup analyses according to ethnicity of participants revealed that rs1501299 and rs2241766 polymorphisms were both significantly correlated with PCOS risk in Caucasians. In addition, rs1501299 polymorphism was also significantly correlated with PCOS risk in East Asians.

Conclusions

Our findings indicated that rs1501299 and rs2241766 polymorphisms might serve as genetic biomarkers of PCOS in certain ethnicities.

     

Association of adiponectin gene polymorphisms with the risk of ischemic stroke in a Chinese Han population

Adiponectin is inversely associated with the risk of ischemic stroke through its anti-inflammatory and anti-atherogenic effects. Genetic variations in the adiponectin gene (ADIPOQ) have been shown to be associated with the risk of ischemic stroke in Caucasians and Japanese populations. However, it was unknown whether variations in the ADIPOQ gene were associated with the risk of ischemic stroke in Chinese population. A case-control study was performed among 302 patients with ischemic stroke and 338 unrelated controls in a Chinese Han population. The single-nucleotide polymorphisms (SNPs) rs266729 (−11377C/G), rs2241766 (+45T/G), rs1501299 (+276G/T) in the ADIPOQ gene were genotyped by the polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) method. The frequencies of GG genotype and G allele of rs266729 in the patients with ischemic stroke were significantly higher than those in the controls (P = 0.034, P = 0.010, respectively). In univariate logistic analysis, compared with CC genotype, GG genotype of rs266729 increased the risk of ischemic stroke (odds ratio (OR) = 2.062, 95% confidence interval (CI) = 1.145–3.715, P = 0.016). After adjustment for potential risk factors by the multivariate logistic analysis, rs266729 remained positive correlation with ischemic stroke (OR = 2.165; 95% CI = 1.116–4.197, P = 0.022). However, no significant association was observed among rs2241766, rs1501299 and ischemic stroke. In addition, no significant difference was found in haplotype frequencies between the patients with ischemic stroke and control subjects. The present study demonstrated that the promoter polymorphism rs266729 of the ADIPOQ gene was associated with an increased risk of ischemic stroke in the Chinese Han population.     

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.     

Genetic Variations in ADIPOQ Gene Are Associated with Chronic Obstructive Pulmonary Disease

Background

Adiponectin is reported to be related to the development of chronic obstructive pulmonary disease (COPD). Genetic variants in the gene encoding adiponectin (ADIPOQ) have been reported to be associated with adiponectin level in several genome–wide linkage and association studies. However, relatively little is known about the effects of ADIPOQ gene variants on COPD susceptibility. We determined the frequencies of single-nucleotide polymorphisms (SNPs) in ADIPOQ in a Chinese Han population and their possible association with COPD susceptibility.

Methods

We conducted a case–control study of 279 COPD patients and 367 age- and gender-distribution-matched control subjects. Seven tagging SNPs in ADIPOQ, including rs710445, rs16861205, rs822396, rs7627128, rs1501299, rs3821799 and rs1063537 were genotyped by SNaPshot. Association analysis of genotypes/alleles and haplotypes constructed from these loci with COPD was conducted under different genetic models.

Results

The alleles or genotypes of rs1501299 distributed significantly differently in COPD patients and controls (allele: P = 0.002, OR = 1.43 and 95%CI = 1.14–1.79; genotype: P = 0.008). The allele A at rs1501299 was potentially associated with an increased risk of COPD in all dominant model analysis (P = 0.009; OR: 1.54; 95%CI: 1.11–2.13), recessive model analyses (P = 0.015; OR: 1.75; 95% CI: 1.11–2.75) and additive model analyses (P = 0.003; OR: 2.11; 95% CI: 1.29–3.47). In haplotype analysis, we observed haplotypes AAAAACT and GGACCTC had protective effects, while haplotypes AGAACTC, AGGCCTC, GGAACTC, GGACACT and GGGCCTC were significantly associated with the increased risk of COPD.

Conclusions

We conducted the first investigation of the association between the SNPs in ADIPOQ and COPD risk. Our current findings suggest that ADIPOQ may be a potential risk gene for COPD. Further studies in larger groups are warranted to confirm our results.     

Gene Polymorphisms of ADIPOQ +45T>G,UCP2 -866G>A,and FABP2 Ala54Thr on the Risk of Colorectal Cancer: A Matched Case-Control Study

As insulin resistance (IR) is an established risk factor for colorectal cancer (CRC), we explored the association between each of the IR-related gene polymorphisms of adiponectin (ADIPOQ) rs2241766, uncoupling protein 2 (UCP2) rs659366, and fatty acid-binding protein (FABP2) rs1799883 and CRC risk. Genotyping of blood samples and collection of lifestyle and dietary habits were performed for 400 case-control pairs. Unconditional logistic regression (ULR) was applied to assess the effects of the three single nucleotide polymorphisms (SNP), environmental factors. Both ULR and generalized multifactor dimensionality reduction (GMDR) were used to test the gene-gene and gene-environment interactions on CRC risk. Subjects carrying the ADIPOQ rs2241766 TG+GG genotype had a higher CRC risk than those carrying the TT genotype (OR = 1.429, 95% CI 1.069–1.909). The additive and multiplicative interactions between ADIPOQ rs2241766 and FABP2 rs1799883 on CRC were found by ULR (RERI = 0.764, 95%CI 0.218∼1.311, AP = 0.514, 95%CI 0.165∼0.864, S = −1.745, 95%CI is unachievable, and P_multi = 0.017, respectively). Furthermore, the high order gene-gene interaction of the three SNPs were found by GMDR (P = 0.0107). A significant dosage effect with an increasing number of risk genotypes was observed as the risk of CRC increased (P_trend = 0.037). In GMDR, the gene-environment interaction among the three SNPs and red meat consumption on CRC risk was significant (P = 0.0107). Compared with subjects with low red meat consumption and null risk genotypes, those with high-red meat consumption and three risk genotypes had 3.439-fold CRC risk (95% CI 1.410–8.385). In conclusion, the results showed that the ADIPOQ rs2241766 TG+GG genotype increased CRC risk. Given the complexity of the carcinogen for CRC, ADIPOQ rs2241766, UCP2 rs659366, FABP2 rs1799883 and red meat consumption potentially worked together in affecting CRC risk.     

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 adiponectin promoter variants with traits and clusters of metabolic syndrome in Arabs: Family-based study

Plasma levels of adiponectin are decreased in type 2 diabetes, obesity and hypertension. Our aim was to use a family-based analysis to identify the genetic variants of the adiponectin (ADIPOQ) gene that are associated with obesity, insulin resistance, dyslipidemia and hypertension, among Arabs. We screened 328 Arabs in one large extended family for single nucleotide polymorphisms (SNPs) in the promoter region of the ADIPOQ gene. Two common SNPs were detected: rs17300539 and rs266729. Evidences of association between traits related to the metabolic syndrome and the SNPs were studied by implementing quantitative genetic association analysis. Results showed that SNP rs266729 was significantly associated with body weight (p-value = 0.001), waist circumference (p-value = 0.037), BMI (p-value = 0.015) and percentage of total body fat (p-value = 0.003). Up to 4.1% of heritability of obesity traits was explained by the rs266729 locus. Further cross-sectional analysis showed that carriers of the G allele had significantly higher values of waist circumference, BMI and percentage of total body fat (p-values 0.014, 0.004 and 0.032, respectively). No association was detected between SNP rs266729 and other clusters of metabolic syndrome or their traits except for HOMA-IR and fasting plasma insulin levels, p-values 0.035 and 0.004, respectively. In contrast, both measured genotype and cross-sectional analysis failed to detect an association between the SNP rs17300539 with traits and clusters of metabolic syndrome. In conclusion, we showed family-based evidence of association of SNP rs266729 at ADIPOQ gene with traits defining obesity in Arab population. This is important for future prediction and prevention of obesity in population where obesity is in an increasing trend.     

Adiponectin gene polymorphism is selectively associated with the concomitant presence of metabolic syndrome and essential hypertension

Objective

Cardiovascular risk increases with the presence of both metabolic syndrome (MetS) and hypertension (HTN). Although the adiponectin (ADIPOQ) gene has been reported to be involved in MetS, its association with HTN remained undetermined. This study aimed to investigate the association of ADIPOQ gene with the phenotypes of HTN and MetS.

Methods

A total of 962 participants from 302 families from the Taiwan young-onset hypertension genetic study were enrolled. Plasma adiponectin were measured, and association analysis was conducted by using GEE regression-based method. Another study, of 1448 unrelated participants, was conducted to replicate the association between ADIPOQ gene and variable phenotypes of MetS with or without HTN.

Results

Among 962 subjects from family samples, the lowest plasma adiponectin value was observed in MetS with HTN component (9.3±0.47 µg/ml) compared with hypertensives (13.4±0.74 µg /ml) or MetS without HTN (11.9±0.60 µg/ml, P<0.05). The SNP rs1501299 (G276T) in ADIPOQ gene was found associated with the presence of HTN in MetS (odds ratio for GG+GT vs. TT = 2.46; 95% CI: 1.14-5.3, p = 0.02), but not rs2241766 (T45G). No association of ADIPOQ gene with HTN alone or MetS without HTN was observed. The significant association of the SNP rs1501299 (G276T) with the phenotype of presence of HTN in MetS was confirmed (odds ratio for GG+GT vs. TT = 2.15; 95% CI: 1.1–4.3) in the replication study.

Conclusions

ADIPOQ genetic variants were selectively and specifically associated with the concomitant presence of MetS and HTN, suggesting potential genetic linkage between MetS and HTN.     

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.     

VEGF +936C/T and +460C/T gene polymorphisms and oral cancer risk: a meta-analysis

Many studies have examined the association between the VEGF +936C/T (rs833061) and +460C/T (rs3025039) gene polymorphisms and oral cancer risk in various populations, but their results have been inconsistent. To assess this relationship more precisely, we performed a meta-analysis. The PubMed, Embase, Web of Science, and China National Knowledge Infrastructure databases were searched for case–control studies that were published up to January 2013. Data were extracted and pooled odds ratios (ORs) with 95 % confidence intervals (CIs) were calculated. Ultimately, six studies were included, comprising 1006 oral cancer cases and 1016 controls. Overall, the pooled OR for VEGF +936 T allele carriers (TC + TT) versus the wild-type homozygotes (CC) was 1.28 (95 % CI 1.04–1.58; P = 0.228 for heterogeneity), the pooled OR for TT versus CC was 1.64 (95 % CI 1.34–1.98; P = 0.315 for heterogeneity), and the pooled OR for the T allele versus the C allele was 1.42 (95 % CI 1.22–1.76; P = 0.286 for heterogeneity). In the stratified analysis by ethnicity, significant risks were found among Caucasians but not Asians. However, there were no associations between VEGF +460C/T and oral cancer risk in only two of the included studies. In conclusion, this meta-analysis demonstrates that the VEGF +936 T allele may be associated with an increased risk of oral cancer, especially among Caucasian populations.     

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.     

Association of Adiponectin Gene (ADIPOQ) rs2241766 Polymorphism with Obesity in Adults: A Meta-Analysis

Background

Adiponectin plays an important role in regulating glucose levels and fatty acid oxidation. Multiple studies have assessed the association between rs2241766 polymorphism in the adiponectin (ADIPOQ) gene and obesity susceptibility. However, the results are inconsistent and inconclusive. The aim of this meta-analysis was to investigate this association in adults.

Method

Several electronic databases were searched for relevant literature published up to November 2013. Statistical analyses were performed using software Review Manager (Version 5.02) and STATA (Version 10.0). The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated with a random-effects model or a fixed-effect model depending on heterogeneity among studies. Q tests and Egger’s tests were performed to assess heterogeneity and publication bias. Sensitivity analysis was conducted to confirm the reliability and stability of the meta-analysis.

Results

A total of 2,819 obese and 3,024 controls in 18 case-control studies were included in the meta-analysis. The results indicated that compared with TT genotype, the ADIPOQ-rs2241766 GG genotype was associated with an increased risk for obesity (OR = 1.39, 95% CI: 1.11–1.73, P for heterogeneity = 0.520, I² = 0%) in overall studies. Whereas, GT genotype was associated with a borderland increased risk for obesity (OR = 1.13, 95% CI: 0.94–1.36, P for heterogeneity = 0.006, I² = 51%). The susceptibility of obesity was increased based on genotypes of TT<GT<GG (P for trend = 0.011). Subgroup analysis of different regions revealed that the ADIPOQ-rs2241766 GG genotype increased obesity risk in the Chinese studies (OR = 1.54, 95% CI: 1.19–2.00) but not in the non-Chinese studies (OR = 1.02, 95% CI: 0.66–1.58). Similar results were observed in allelic, recessive, and dominant genetic models. There was no significant evidence of publication bias in the overall, Chinese, and non-Chinese studies (P = 0.426, P = 0.935, and P = 0.390, respectively).

Conclusion

The results of this meta-analysis suggest that the ADIPOQ-rs2241766 G/T polymorphism might be associated with obesity in Chinese studies but not in non-Chinese studies in adults. Better-designed studies that consider confounding factors and assess larger sample sizes with a focus on ADIPOQ-rs2241766G/T polymorphisms and obesity are required in the future.     

ADIPOQ,KCNJ11 and TCF7L2 polymorphisms in type 2 diabetes in Kyrgyz population: A case‐control study

The aim of this study was to ascertain the polymorphic markers profile of ADIPOQ, KCNJ11 and TCF7L2 genes in Kyrgyz population and to analyze the association of polymorphic markers and combinations of ADIPOQ gene's G276T locus, KCNJ11 gene's Glu23Lys locus and TCF7L2 gene's VS3C>T locus with type two diabetes (T2D) in Kyrgyz population. In this case‐control study, 114 T2D patients 109 non‐diabetic participants were genotyped using polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP). Two individual polymorphisms (ADIPOQ rs1501299, KCNJ11 rs5219) were found to be associated with T2D. We found two (Lys23Lys/CC and Glu23Lys/CT) of the overall nine combinations, which were more prevalent in T2D group compared to controls (χ² = 4.21, P = 0.04). Lys23Lys/CC combination was associated with a 2.65‐fold increased likelihood of T2D (OR = 2.65, 95% CI 1.12‐6.28), whereas the Glu23Lys/CT combination also increased such likelihood (OR = 3.88, 95% CI 1.27‐11.91). This study demonstrated some association of 276T allele and ADIPOQ gene G276T heterozygous genotype as well as KCNJ11 gene 23Lys allele with T2D in ethnic Kyrgyz, but study results should be interpreted with caution because of the limited statistical power.     

Adiponectin gene polymorphisms in Egyptian type 2 diabetes mellitus patients with and without diabetic nephropathy

Recently, several reports addressed the associations of adiponectin (ADIPOQ) gene polymorphisms with abnormal adiponectin serum levels, type 2 diabetes mellitus (T2DM), and diabetic nephropathy (DN); however, results are inconsistent. This study aimed to investigate the possible association of ADIPOQ gene polymorphisms with T2DM and/or DN and whether they affect serum adiponectin levels in Egyptian population. Two hundred and ninety-six T2DM patients (100 normoalbuminuric patients, 103 microalbuminuric patients, and 93 macroalbuminuric patients) and 209 controls were enrolled in the present study. Polymorphisms of +45, ?11391, and +276 of the ADIPOQ gene were detected using polymerase chain reaction restriction fragment length polymorphism. Serum adiponectin was measured using ELISA. Our results revealed that ADIPOQ +45 TG and GG genotypes and G allele were significantly associated with T2DM, micro/macroalbuminuria, and decreased serum adiponectin level. ADIPOQ ?11391 AA genotype frequency was significantly increased in T2DM group. Moreover, GA and AA genotypes and A allele of ADIPOQ ?11391 were significantly associated with susceptibility to macroalbuminuria despite increased serum adiponectin concentrations. While, ADIPOQ +276 TT genotype and T allele were protective factors regarding the susceptibility to T2DM and micro/macroalbuminuria, and they were significantly associated with increased adiponectin levels. We observed also that the decrease of the serum Adiponectin level was accompanied by an insulin resistance, albuminuria, as well as an increase of serum creatinine. We concluded that ADIPOQ +45; ADIPOQ ?11391 gene polymorphisms are associated with T2DM and/or DN in Egyptian population. While, ADIPOQ +276 gene polymorphism is a protective factor regarding T2DM and/or DN susceptibility.     

Programmed Cell Death-1 Polymorphisms Decrease the Cancer Risk: A Meta-Analysis Involving Twelve Case-Control Studies

Programmed cell death-1 (PD-1) plays an important inhibitory role in anti-tumor responses, so it is considered as a powerful candidate gene for individual’s genetic susceptibility to cancer. Recently, some epidemiological studies have evaluated the association between PD-1 polymorphisms and cancer risk. However, the results of the studies are conflicting. Therefore, a meta-analysis was performed. We identified all studies reporting the relationship between PD-1 polymorphisms and cancers by electronically searches. According to the inclusion criteria and the quality assessment of Newcastle-Ottawa Scale (NOS), only high quality studies were included. A total of twelve relevant studies involving 5,206 cases and 5,174 controls were recruited. For PD-1.5 (rs2227981) polymorphism, significantly decreased cancer risks were obtained among overall population, Asians subgroup and population-based subgroup both in TT vs. CC and TT vs. CT+CC genetic models. In addition, a similar result was also found in T vs. C allele for overall population. However, there were no significant associations between either PD-1.9 (rs2227982) or PD-1 rs7421861 polymorphisms and cancer risks in all genetic models and alleles. For PD-1.3 (rs11568821) polymorphism, we found different cancer susceptibilities between GA vs. GG and AA vs. AG+GG genetic models, and no associations between AA vs. GG, AA+AG vs. GG genetic models or A vs. G allele and cancer risks. In general, our results firstly indicated that PD-1.5 (rs2227981) polymorphism is associated a strongly decreased risk of cancers. Additional epidemiological studies are needed to confirm our findings.     

Influence of the interaction between the adiponectin G276T polymorphism and body mass index on lipid levels in healthy children

Adiponectin is an adipose tissue-specific hormone which is inversely associated with metabolic alterations related to atherosclerosis. Polymorphisms in the adiponectin gene (AdipoQ) have been related to low adiponectin levels as well as several cardiovascular risk factors, but this association remains controversial. In our study we investigated the relationship between the AdipoQ T45G (rs: 2241766) and G276T (rs: 1501299) polymorphisms and adiponectin concentrations, blood pressure, and lipid and insulin levels, in a population-based sample of 12- to 16-year-old children. The study included 815 healthy Spanish children (388 boys and 427 girls). Plasma glucose and lipid levels were determined by standard methods. Insulin concentrations were measured by RIA, and serum adiponectin levels were determined by ELISA. The AdipoQ T45G and AdipoQ G276T polymorphisms were determined by TaqMan^® allelic discrimination assays. ANOVA or t test allowed for comparison of the studied parameters across genotypes or genotype groups, respectively. A linear regression analysis was performed to examine the independent relationships of the lipid variables with BMI (body mass index), AdipoQ G276T polymorphism and the interaction between the two. When independently comparing the effect of these polymorphisms in normal-weight and overweight children, we observed that overweight boys carriers of the minor allele T had significantly lower TC, LDL-C and apo A-I levels than non-carriers, but these differences were not apparent in normal-weight boys. Furthermore, linear regression analysis demonstrated that interaction between the BMI and the AdipoQ G276T polymorphism is a significant factor explaining the variations of TC and LDL-C levels. To our knowledge, this is the first study to report an association between the AdipoQ G276T polymorphism and lipid levels in overweight boys alone, thereby suggesting that the influence of the AdipoQ polymorphisms on cardiovascular risk factors may be dependent on BMI.     

Association of four insulin resistance genes with type 2 diabetes mellitus and hypertension in the Chinese Han population

Insulin resistance plays an important role in the development of type 2 diabetes mellitus (T2DM) and hypertension. The purpose of the present study was to evaluate the association between four insulin resistance genes (ADIPOQ, LEPR, RETN, and TRIB3) and both T2DM and hypertension. A total of 768 Han Chinese subjects were recruited into this study, including 188 cases who had T2DM alone, 223 cases who had hypertension alone, 181 cases with both T2DM and hypertension, and 176 control subjects with neither T2DM nor hypertension. Twenty-three tag SNPs in four insulin resistance genes were genotyped and analyzed for association with T2DM and hypertension. One intron SNP (rs13306519) in LEPR and one 3′UTR SNP (rs1063537) in ADIPOQ demonstrated a significant association with T2DM (P = 0.024 and 0.014 respectively). Another intron SNP (rs12037879) in LEPR and a promoter region SNP (rs266729) in ADIPOQ were significantly associated with hypertension (P = 0.041 and 0.042, respectively). These associations survived the permutation test (P = 0.023, 0.018, 0.026, and 0.035, respectively). These associations were still found to be significant in the additive model after adjusting for potential confounding factors including age, sex, BMI, HDL, LDL, total cholesterol, and triglyceride levels (P = 0.024, 0.016, 0.04, and 0.043, respectively). No other gene variants were found to be significantly associated with T2DM or hypertension (P > 0.05). None of the studied gene variants were found to be significantly associated with T2DM+ hypertension (P > 0.05). A significant interaction was observed between two SNPs rs13306519 in LEPR and rs266729 in ADIPOQ for T2DM (P_int = 0.012, OR_int = 2.67) and hypertension (P_int = 0.0041, OR_int = 2.23). These findings suggest that variants in ADIPOQ and LEPR are risk factors for T2DM and hypertension in the Chinese population and that variants in RETN and TRIB3 are not major risk factors for these diseases.