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 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.     

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 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.     

Polymorphisms of CHRNA5-CHRNA3-CHRNB4 Gene Cluster and NSCLC Risk in Chinese Population

AIM: To explore the potential association between single-nucleotide polymorphisms (SNPs) and haplotypes of the CHRNA5-CHRNA3-CHRNB4 gene cluster and the non-small cell lung cancer (NSCLC) susceptibility in never-smoking Chinese. METHODS: A case-control study was conducted with 200 NSCLC patients and 200 healthy controls, matched on age and sex. Five SNPs distributed in CHRNA5-CHRNA3-CHRNB4 gene cluster were selected for genotyping. The association between genotype and lung cancer risk was evaluated by computing the odds ratio (OR) and 95% confidence interval (CI) from multivariate unconditional logistic regression analyses with adjustment for gender and age. RESULTS: For CHRNA3 rs578776 status, data were available in 199 NSCLC patients and 199 controls. The G/G homozygote in CHRNB4 rs7178270 had a reduced risk of developing NSCLC (OR = 0.553; 95% CI = 0.309–0.989; P = .0437), especially squamous cell carcinoma (SQC) (OR = 0.344; 95% CI = 0.161–0.732; P = .0043), compared with those who carry at least one C allele (C/C and C/G). The polymorphisms of rs578776, rs938682, rs17486278, and rs11637635 were not significantly different between controls and cases or between controls and histologic subgroups, adenocarcinoma and SQC, respectively. CONCLUSIONS: In our study, we found that the SNP of CHRNB4 rs7178270 is significantly associated with reduced risk of NSCLC, especially with reduced risk of SQC in never-smoking Chinese population.     

The IL-17F sequence variant is associated with susceptibility to tuberculosis

The interleukin (IL)-17 gene plays a key role in host defence against infections from microbes, including Mycobacterium tuberculosis. Genetic factors contribute to host defence. However, whether genetic variation in IL-17 is associated with altered susceptibility to tuberculosis is unknown. A total of 596 pulmonary tuberculosis (PTB) patients, 176 extra-pulmonary tuberculosis (EPTB) patients, and 622 control patients from a Chinese Han population were recruited. Two single-nucleotide polymorphisms (SNPs) in IL-17F (rs1889570 and rs763780) and one SNP in IL-17A (rs2275913) were genotyped using the SNaPshot technique. Of the three SNPs in the IL-17 gene tested, there was an increased frequency of the rs1889570 G allele and the rs763780 C allele in the PTB patients and an increased frequency of the rs763780 C allele in the EPTB patients compared with the control patients. There were also significant differences in the distribution of the rs763780 genotype between the PTB and EPTB patients and the controls. The patients who had the CT/TT genotype of the rs763780 SNP were more susceptible to tuberculosis, compared to the CC genotype. There was no significant difference observed between the IL-17 SNPs when the PTB and EPTB patients were compared. Genetic variation in IL-17F is associated with altered susceptibility to tuberculosis and may provide valuable information in the development of tuberculosis.     

单羧酸转运蛋白基因SNP 与肝细胞肝癌预后的关联研究

目的:探讨单羧酸转运蛋白基因(monocarboxylate transporter,MCT)单核苷酸多态性(single nucleotide polymorphism,SNPs)与肝细胞肝癌(hepatocellular carcinoma,HCC)根治术患者预后的关系。方法:运用Sequenom i PLEX分型技术对830例原发性HCC患者MCT家族(MCT1、MCT2和MCT4)基因上的8个功能性SNP位点进行基因分型,并分析这些SNP与HCC患者预后的相关性。结果:MCT1基因rs1049434位点和MCT2基因rs995343位点基因型与HCC患者总体生存期及无复发生存期均显著相关(P0.05)。携带MCT1 AT基因型或TT基因型的患者死亡及复发风险均显著低于携带AA基因型的患者(HR=0.72;P=0.042或HR=0.64;P=0.002);携带MCT2 CT基因型或TT基因型的患者死亡及复发风险均显著高于携带CC基因型的患者(HR=1.64;P=0.018或HR=1.52;P=0.026)。而且,MCT1基因rs1049434位点和MCT2基因rs995343位点对HCC预后存在显著的累积效应,携带2个危险基因型的患者死亡及复发风险分别是没有危险基因型患者的2.16倍和2.54倍。此外,携带2个危险基因型的HCC患者在术后行TACE辅助治疗后死亡及复发风险均显著降低(P0.05)。结论:MCT1和MCT2基因上的功能性SNP位点有可能作为HCC根治术后预后评估和TACE辅助治疗反应预测的独立标志物。     

Association between microRNA-146a, -499a and -196a-2 SNPs and non-small cell lung cancer: a case–control study involving 2249 subjects

MicroRNA (miR) acts as a negative regulator of gene expression. Many literatures have suggested that miRs may be involved in the process of cell proliferation, inflammation, oxidative stress, energy metabolism and epithelial–mesenchymal transition. Thus, miRs may be implicated in the occurrence of non-small cell lung cancer (NSCLC). In the current investigation, we included 2249 subjects (1193 NSCLC patients and 1056 controls) and designed a study to identify the relationship of miR-146a rs2910164 C/G, -499a rs3746444 A/G and -196a-2 rs11614913 T/C with the risk of NSCLC. The risk factors (e.g., body mass index (BMI), sex, smoking, drinking and age) was used to adjust the odds ratios (ORs) and 95% confidence intervals (CIs). After conducting a power value assessment, we did not confirm that the miR-single nucleotide polymorphisms (SNPs) genotypic distributions were different in NSCLC cases and controls. However, the association of miR-196a-2 rs11614913 with a decreased risk of NSCLC was identified in the female subgroup (adjusted P=0.005, power = 0.809 for TC vs. TT, and adjusted P=0.004, power = 0.849 for CC/TC vs. TT). In addition, gene–gene interaction analysis showed that rs11614913 TC/3746444 AA and rs11614913 CC/rs3746444 AA could also reduce the susceptibility to NSCLC (rs11614913 TC/rs3746444 AA vs. rs11614913 TT/rs3746444 AA, P=0.001, power = 0.912 and rs11614913 CC/rs3746444 AA vs. rs11614913 TT/rs3746444 AA, P=0.003, power = 0.836). In conclusion, in overall comparisons, we did not confirm that the rs2910164, rs3746444, and rs11614913 SNPs genotypic distributions were different in NSCLC cases and controls. However, this case–control study demonstrates that miR-196a-2 rs11614913 may be a protective factor for the development of NSCLC among female patients.     

Lack of evidence for intermolecular epistatic interactions between adiponectin and resistin gene polymorphisms in Malaysian male subjects

Epistasis (gene-gene interaction) is a ubiquitous component of the genetic architecture of complex traits such as susceptibility to common human diseases. Given the strong negative correlation between circulating adiponectin and resistin levels, the potential intermolecular epistatic interactions between ADIPOQ (SNP+45T > G, SNP+276G > T, SNP+639T > C and SNP+1212A > G) and RETN (SNP-420C > G and SNP+299G > A) gene polymorphisms in the genetic risk underlying type 2 diabetes (T2DM) and metabolic syndrome (MS) were assessed. The potential mutual influence of the ADIPOQ and RETN genes on their adipokine levels was also examined. The rare homozygous genotype (risk alleles) of SNP-420C > G at the RETN locus tended to be co-inherited together with the common homozygous genotypes (protective alleles) of SNP+639T > C and SNP+1212A > G at the ADIPOQ locus. Despite the close structural relationship between the ADIPOQ and RETN genes, there was no evidence of an intermolecular epistatic interaction between these genes. There was also no reciprocal effect of the ADIPOQ and RETN genes on their adipokine levels, i.e., ADIPOQ did not affect resistin levels nor did RETN affect adiponectin levels. The possible influence of the ADIPOQ gene on RETN expression warrants further investigation.     

Adiponectin gene haplotype is associated with preeclampsia

We determined whether the polymorphism of the gene encoding adiponectin contributes to susceptibility to preeclampsia. The study involved 133 Finnish women with preeclampsia and 245 healthy control subjects. All women were genotyped for two single nucleotide polymorphisms (SNPs), SNP45 in exon 2 and SNP276 in intron 2, in the adiponectin gene. Chi2 analysis was used to assess genotype and allele frequency differences between the preeclamptic and control groups. In addition, the pair of loci haplotype analysis, using the expectation-maximization (EM) algorithm, was used to examine the estimated haplotype frequencies of the two SNPs, among the two groups. The TT genotype versus the pooled G genotypes in SNP276 was associated with protection against preeclampsia (p = 0.012) at an odds ratio of 0.27 (95% confidence interval [CI]: 0.09-0.80). Also the genotype and allele frequency distributions of SNP276 differed significantly between the preeclampsia group and the control group (p = 0.035 and p = 0.043, respectively). Single-point genotype and allele distributions in SNP45 of the adiponectin gene were not statistically different between the groups. In the haplotype estimation analysis, the pooled G haplotypes versus the TT haplotype were significantly overrepresented in the preeclampsia group (p = 0.042 +/- 0.005). Polymorphisms of the adiponectin gene show a weak, but statistically significant, haplotype association with susceptibility to preeclampsia in Finnish women.     

Associations of SNPs in ADIPOQ and subclinical cardiovascular disease in the multi-ethnic study of atherosclerosis (MESA)

Circulating adiponectin is associated with both clinical and subclinical cardiovascular disease (CVD). Variants of the adiponectin gene (ADIPOQ) are associated with clinical CVD, but little is known about associations with subclinical CVD. We studied the association of 11 ADIPOQ single-nucleotide polymorphisms (SNPs) with common and internal carotid intima media thickness (cIMT), presence of coronary artery calcification (CAC), and CAC scores (in those with CAC) in 2,847 participants in the Multi-Ethnic Study of Atherosclerosis (MESA). Participants were white (n = 712), African American (n = 712), Chinese (n = 718), and Hispanic (n = 705). All models were adjusted for age, sex, and field site, and stratified by race/ethnic group. African Americans with genotypes AG/GG of rs2241767 had 36% greater (95% confidence interval (CI; 16%, 59%), P = 0.0001) CAC prevalence; they also had a larger common cIMT (P = 0.0043). Also in African Americans, genotypes AG/AA of rs1063537 were associated with a 35% (95% CI (14%, 59%), P = 0.0005) greater CAC prevalence. Hispanics with the AA genotype of rs11711353 had a 37% (95% CI (14%, 66%), P = 0.0011), greater CAC prevalence compared to those with the GG genotype. Additional adjustment for ancestry in African-American and Hispanic participants did not change the results. No single SNP was associated with subclinical CVD phenotypes in Chinese or white participants. There appears to be an association between ADIPOQ SNPs and subclinical CVD in African Americans and Hispanics. Replication as well as assessment of other ADIPOQ SNPs is warranted.     

Adiponectin Gene Polymorphism rs2241766 T/G Is Associated with Response to Pioglitazone Treatment in Type 2 Diabetic Patients from Southern China

Introduction

Insulin sensitizing drugs such as pioglitazone are not uniformly treatment effective among individual type 2 diabetic patients. Here, the relationship of pioglitazone efficacy to single nucleotide polymorphisms (SNP) of the adiponectin gene, a critical gene directly regulated by the drug, was examined in a cohort of Chinese Han type 2 diabetic patients.

Methods

Eighty type 2 diabetic patients were treated with pioglitazone (15 mg/day) for 12 weeks without interruption of their current therapeutic regimen. Fasting plasma glucose, fasting insulin, homeostasis model assessment for insulin resistance (HOMA-IR), and glycated hemoglobin (HbA1c%) were collected both prior to and following pioglitazone treatment. Response to pioglitazone was defined as a decrease of at least 15% in HbA1c% levels. Three regions of the adiponectin gene containing SNPs (promoter, intron 2 and exon 2, and exon 3) were amplified and sequenced to determine genotype.

Results

Serum adiponectin levels were significantly increased (p<0.001) whereas fasting plasma glucose, fasting insulin, HOMA-IR, and HbA1c% values were significantly decreased relative to baseline measurements (p<0.001). Response of patients with TG and TT genotypes at rs2241766 (exon2; 52.9% vs. 12.7%, respectively p = 0.001) was statistically significant relative to all other patients. Amongst rs2241766 TG and TT patients, the mean decrease in HbA1c% levels was greater where the genotype was TG (1.15±0.80 vs. 0.52±0.64, p = 0.001).

Conclusions

The adiponectin gene polymorphism rs2241766 T/G is associated with pioglitazone efficacy in type 2 diabetic patients, and status of the polymorphism may be an important clinical factor to consider prior to pioglitazone treatment.     

Association between common genetic variants in pre-microRNAs and gastric cancer risk in Japanese population

Background: Common single‐nucleotide polymorphisms (SNPs) in microRNAs (miRNA) have been shown to be associated with susceptibility to several human cancers. We evaluated the associations of three SNPs (rs11614913, rs2910164, and rs3746444) in pre‐miRNAs (miR‐196a2, miR‐146a, and miR‐499) with the risk of gastric cancer (GC) and peptic ulcer diseases, and with the severity of Helicobacter pylori‐induced gastritis in Japanese population. Methods: The rs11614913 (C>T), rs2910164 (G>C), and rs3746444 (A>G) SNPs were genotyped in 552 GC, and 697 non‐cancer subjects, including 141 gastric and 73 duodenal ulcer, and 483 non‐ulcer subjects. The degree of histologic gastritis was classified according to the updated Sydney System, and the serum pepsinogen levels were measured in selected 579 and 204 cases. Results: The rs2910164 CC genotype held a significantly higher risk of GC when compared to non‐cancer subjects (adjusted odds ratio (OR) = 1.30, 95% confidence interval (CI) = 1.02–1.66, p =.03). Similarly, the rs2910164 C carrier was associated with higher risk of GC when compared to both non‐cancer and non‐ulcer subjects (OR = 1.39, 95%CI = 1.00–1.93, p =.05, adjusted OR = 1.57, 95%CI = 1.09–2.27, p =.016, respectively). The rs2910164 CC genotype was associated with non‐cardia and upper third, diffuse type and advanced stage GC. The rs11614913 TT genotype was associated with higher degree of mononuclear cell infiltration (score 0–1 vs 2～, adjusted OR = 1.62, 95%CI = 1.05–2.49, p =.03). Conclusions: The rs2910164 (G>C) SNP in the miR‐146a is associated with susceptibility to GC. In addition, the rs11614913 (C>T) SNP in the miR‐196a2 is associated with the degree of H. pylori‐induced mononuclear cell infiltration.     

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.     

Association of CNR1 and FAAH endocannabinoid gene polymorphisms with anorexia nervosa and bulimia nervosa: evidence for synergistic effects

Endocannabinoids modulate eating behavior; hence, endocannabinoid genes may contribute to the biological vulnerability to eating disorders. The rs1049353 (1359 G/A) single nucleotide polymorphism (SNP) of the gene coding the endocannabinoid CB1 receptor ( CNR1 ) and the rs324420 (cDNA 385C to A) SNP of the gene coding fatty acid amide hydrolase (FAAH), the major degrading enzyme of endocannabinoids, have been suggested to have functional effects on mature proteins. Therefore, we explored the possibility that those SNPs were associated to anorexia nervosa and/or bulimia nervosa. The distributions of the CNR1 1359 G/A SNP and of the FAAH cDNA 385C to A SNP were investigated in 134 patients with anorexia nervosa, 180 patients with bulimia nervosa and 148 normal weight healthy controls. Additive effects of the two SNPs in the genetic susceptibility to anorexia nervosa and bulimia nervosa were also tested. As compared to healthy controls, anorexic and bulimic patients showed significantly higher frequencies of the AG genotype and the A allele of the CNR1 1359 G/A SNP. Similarly, the AC genotype and the A allele of the FAAH cDNA 385C to A SNP were significantly more frequent in anorexic and bulimic individuals. A synergistic effect of the two SNPs was evident in anorexia nervosa but not in bulimia nervosa. Present findings show for the first time that the CNR1 1359 G/A SNP and the FAAH cDNA 385C to A SNP are significantly associated to anorexia nervosa and bulimia nervosa, and demonstrate a synergistic effect of the two SNPs in anorexia nervosa.     

Distribution and genotype frequency of adiponectin (+45 T/G) and adiponectin receptor2 (+795 G/A) single nucleotide polymorphisms in Iranian population

The Adiponectin (ADIPOQ) gene encodes adipose tissue-secreted hormone, Adiponectin, which is secreted to the bloodstream by adipocytes. Adiponectin is a hormone with anti-inflammatory and anti-atherogenic properties and plays a significant role in insulin sensitivity and obesity. The genetic variations in ADIPOQ gene change the circulating adiponectin level and may cause insulin resistance. The aim of the present study is to evaluate the frequency of a common single nucleotide polymorphism (SNP) of ADIPOQ gene (+45T/G) and adiponectin receptor-2 (ADIPOR2) gene (+795G/A) in Iranian population and to correlate these data with other populations. A hundred healthy volunteers were enrolled to identify the genotype of ADIPOQ gene (+45T/G) and ADIPOR2 gene (+795G/A). This was performed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Genotype frequencies for ADIPOQ (+45T/G) were 0.789 for TT, 0.164 for TG, and 0.0468 for GG. Allelic frequencies were 0.87 and 0.13 for T and G, respectively. Genotype frequencies for ADIPOR2 (+795G/A) were 0.09 for AA, 0.3 for AG, and 0.61 for GG; allelic frequencies were 0.24 for A and 0.76 for G. Comparisons between ADIPOQ and ADIPOR2 polymorphisms in Iranian population with those in other populations showed significant differences.     

Genome-wide association study in east Asians identifies novel susceptibility loci for breast cancer

Genetic factors play an important role in the etiology of both sporadic and familial breast cancer. We aimed to discover novel genetic susceptibility loci for breast cancer. We conducted a four-stage genome-wide association study (GWAS) in 19,091 cases and 20,606 controls of East-Asian descent including Chinese, Korean, and Japanese women. After analyzing 690,947 SNPs in 2,918 cases and 2,324 controls, we evaluated 5,365 SNPs for replication in 3,972 cases and 3,852 controls. Ninety-four SNPs were further evaluated in 5,203 cases and 5,138 controls, and finally the top 22 SNPs were investigated in up to 17,423 additional subjects (7,489 cases and 9,934 controls). SNP rs9485372, near the TGF-β activated kinase (TAB2) gene in chromosome 6q25.1, showed a consistent association with breast cancer risk across all four stages, with a P-value of 3.8×10⁻¹² in the combined analysis of all samples. Adjusted odds ratios (95% confidence intervals) were 0.89 (0.85–0.94) and 0.80 (0.75–0.86) for the A/G and A/A genotypes, respectively, compared with the genotype G/G. SNP rs9383951 (P = 1.9×10⁻⁶ from the combined analysis of all samples), located in intron 5 of the ESR1 gene, and SNP rs7107217 (P = 4.6×10⁻⁷), located at 11q24.3, also showed a consistent association in each of the four stages. This study provides strong evidence for a novel breast cancer susceptibility locus represented by rs9485372, near the TAB2 gene (6q25.1), and identifies two possible susceptibility loci located in the ESR1 gene and 11q24.3, respectively.