ADIPOQ Rs1501299 Research Articles

Gene polymorphisms related to insulin resistance and gene–environment interaction in colorectal cancer risk

Background and aim: Insulin resistance (IR) is an established risk factor for colorectal cancer (CRC) and both IR and CRC physiologically overlap. As such, this study explored the relationship of IR-related gene polymorphisms and CRC risk.Subjects and methods: A total of 400 case-control pairs were profiled in terms of their lifestyle, dietary habits and blood sample. Classification and regression tree (CART) and generalized multi-factor dimensionality reduction (GMDR) were employed to test the gene–environment interactions in CRC risk.Results: ADIPOQ rs2241766 TG + GG, ADIPOQ rs1501299 GT + TT and CAPN-10 rs3792267 GA + AA were significantly related to CRC risk. In CART, individuals with high red meat consumption, CAPN-10 rs3792267 GG, ADIPOQ rs1501299 GG and ADIPOQ rs2241766 TG + GG had an OR of 1.821 (95% CI = 1.124–2.951). The overall best GMDR model including the four factors had the maximal TBA (0.5943) and CVC (10/10) (p = 0.0010). Subjects with high red meat consumption and the three risk genotypes had a CRC risk 10.195-times (95% CI = 2.164–48.030) greater than those with low red meat and null risk genotypes.Conclusions: ADIPOQ rs2241766, ADIPOQ rs1501299 and CAPN-10 rs3792267 are significantly associated with CRC risk and the combination of the three polymorphisms and red meat affect CRC risk.

A single nucleotide polymorphism inADIPOQpredicts biochemical recurrence after radical prostatectomy in localized prostate cancer

Adiponectin has been implicated in prostate cancer (PCa) aggressiveness. However, the role of genetic variations in the adiponectin (ADIPOQ) gene in PCa progression remains unknown. To determine whether genetic variants in ADIPOQ are associated with the risk of biochemical recurrence (BCR) after radical prostatectomy (RP). We evaluated three common ADIPOQ polymorphisms in 728 men with clinically localized PCa who underwent RP. Multivariable Cox proportional hazards models and Kaplan-Meier analysis were used to assess their prognostic significance on BCR. The plasma adiponectin concentrations were measured by enzyme-linked immunosorbent assay. ADIPOQ rs182052 variant allele was associated with both increased risk of BCR [HR: 2.44; 95% confidence interval (CI): 1.57-;3.79, P = 6×10-5] and decreased adiponectin level (β = -0.048, P = 0.004). Stratified analyses demonstrated that the association was more pronounced in men with higher visceral adipose tissue. Our data support that the ADIPOQ rs182052 SNP may be a predictive biomarker for BCR after RP by a possible mechanism of altering the adiponectin level. If validated, genetic predictors of outcome may help individualizing treatment for PCa.

ADIPOQ polymorphism rs182052 is associated with clear cell renal cell carcinoma.

Recent studies have indicated that low circulating adiponectin concentrations are associated with a higher risk of several cancers, including renal cell carcinoma. In this case–control study, we examined the frequency of single nucleotide polymorphisms (rs182052G>A, rs266729C>G, and rs3774262G>A) in the adiponectin gene (ADIPOQ) in 1004 patients with clear cell renal cell carcinoma (ccRCC) compared with a group of healthy subjects (n = 1108). Fasting serum adiponectin concentrations were also examined. Logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (95% CI). The association of serum adiponectin concentration with genetic variants was calculated using a multivariate linear regression model. A significantly higher ccRCC risk was associated with the rs182052 variant A allele (adjusted OR, 1.36 and 95% CI, 1.07–1.74 for AA vs GG, P = 0.013; adjusted OR, 1.27 and 95% CI, 1.04–1.56 for AA vs GG+AG, P = 0.019), and this positive association was more evident in overweight subjects. Fasting serum adiponectin was lower in subjects carrying A alleles of rs182052 in both ccRCC patients (β = −0.399, P = 0.018) and healthy controls (β = −0.371, P = 0.024). These results suggest that ADIPOQ rs182052 is significantly associated with ccRCC risk.In this case–control study, we examined the frequency of single nucleotide polymorphisms (rs182052G>A, rs266729C>G, and rs3774262G>A) in the adiponectin gene (ADIPOQ) in 1004 patients with clear cell RCC (ccRCC) compared with a group of healthy subjects (n = 1108). Fasting serum adiponectin concentrations were also examined. Fasting serum adiponectin was lower in subjects carrying minor alleles of rs182052 in both ccRCC patients (β = −0.399, P = 0.018) and healthy controls (β = −0.371, P = 0.024). These results suggest that ADIPOQ rs182052 is significantly associated with ccRCC risk.

ADIPOQ and IL6 variants are associated with a pro-inflammatory status in obeses with cardiometabolic dysfunction

BackgroundPolymorphisms in genes encoding adiponectin (ADIPOQ) and interleukin-6 (IL6) have been associated with adiposity and obese-related phenotypes. This study investigated the relationship of ADIPOQ and IL6 gene polymorphisms with pro-inflammatory and cardiometabolic markers in obese patients.MethodsAnthropometric and body composition parameters were measured in 249 Brazilian subjects (30 to 68 yr). Metabolic and inflammatory markers and adipokines were analyzed in blood samples. ADIPOQ rs2241766 (45 T > G) and IL6 rs1800795 (−174G > C) polymorphisms were analyzed by real-time PCR and PCR-RFLP, respectively.ResultsType 2 diabetes, hypertension, dyslipidemia and increased values of waist circumference, body fat, leptin, fibrinogen, IL-1β, hsCRP and TNFα were related to obesity (p < 0.05). Multiple linear regression analysis showed a positive correlation between BMI and waist circumference, body fat, leptin, fibrinogen, PAI-1, IL-1β, hsCRP and TNFα values (p < 0.001) but not with adiponectin. Obese group had altered metabolic status, resistance to leptin and insulin, and atherogenic and pro-inflammatory profiles. ADIPOQ and IL6 variants were not directely related to obesity, leptin resistance or alterations in cardiometabolic markers. Individuals carrying ADIPOQ 45G allele (TG + GG genotype) had higher IL-6, IL-1β and TNFα levels than TT genotype carriers (p < 0.05). IL6 -174GG genotype was associated with increased IL-1β levels (p = 0.033).ConclusionObesity is associated with leptin resistance, cardiometabolic alterations and a pro-inflammatory status. Our results are suggestive that ADIPOQ and IL6 polymorphisms contribute to cardiometabolic risk in obese individuals.

Association between adiponectin polymorphisms and the risk of colorectal cancer.

To discuss the association between adiponectin (ADIPOQ) gene rs2241766 and rs1501299 polymorphisms and the risk of colorectal cancer, and to analyze the role of the interaction between these two loci and environmental factors in colorectal cancer pathogenesis. The case-control study was performed with a 1:1 match. A self-designed questionnaire was used to perform a face-to-face survey with 600 new primary colorectal cancer cases confirmed by histopathology as well as 600 cases of people receiving a physical examination at the same time. The general information, lifestyle, and diet habits, etc. were collected from two groups of study subjects. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to identify ADIPOQ rs2241766 and rs1501299 genotypes. After adjusting for factors such as colorectal cancer family history, body-mass index (BMI), daily sedentary time, weekly red meat intake frequency, as well regular tea drinking, conditional logistic regression analysis indicated that rs2241766 TG+GG carriers had a higher risk of colorectal cancer than TT carriers (OR=1.433, 95% CI: 1.014-1.985); rs1501299 GT+TT carriers had a lower risk of colorectal cancer than GG carriers (OR=0.723, 95% CI: 0.531-0.902). Generalized multifactor dimensionality reduction analysis showed that ADIPOQ rs2241766 and rs1501299 could have interaction with red meat intake (p=0.001). ADIPOQ rs2241766 and rs1501299 single nucleotide polymorphisms (SNPs) could be associated with colorectal pathogenesis and could have interactions with red meat intake. Both factors impact colorectal cancer occurrence.

Adiponectin Gene Polymorphisms are Associated with Increased Risk of Colorectal Cancer.

BackgroundThis meta-analysis investigates the associations of adiponectin (ADIPOQ) genetic polymorphisms with the susceptibility to colorectal cancer (CRC).Material/Methods2 reviewers independently searched 6 databases – PubMed, Cochrane Library, Ovid, Embase, China National Knowledge Infrastructure (CNKI) and Wanfang databases – to identify published studies relevant to adiponectin gene polymorphisms and CRC. Studies retrieved from database searches were screened using our stringent inclusion and exclusion criteria. Full texts of the selected studies were accessed and related data was extracted using a standardized data extraction form. Comprehensive Meta-analysis 2.0 software was used for statistical analyses.ResultsA total of 188 studies were initially retrieved from database search, and 6 studies were eventually selected, through a rigorous screening process, for inclusion in this meta-analysis. The 6 studies contained a total of 1897 patients (Asians: 1190; white: 707) with CRC in case group and 2475 healthy controls (Asians: 1325; white: 1150) in the control group. Results of the current meta-analysis revealed that the rs2241766 T>G single-nucleotide polymorphisms (SNP) increase the risk of CRC; rs1501299 G>T under dominant model was associated with increased risk of CRC; and rs266729 C>G SNP under allele model conferred an increased risk of CRC.ConclusionsOur meta-analysis strongly suggests that the ADIPOQ rs2241766 T>G, rs1501299 G>T, and rs266729 C>G SNPs correlate with an increased risk of CRC.

Associations between variants on ADIPOQ and ADIPOR1 with colorectal cancer risk: a Chinese case-control study and updated meta-analysis.

BackgroundEpidemiological studies have suggested that variants on adiponectin (ADIPOQ) and its receptor ADIPOR1 (adiponectin receptor 1) are associated with colorectal cancer (CRC) risk; however, the results were inconclusive. The aim of the study was to evaluate the associations between the variants on ADIPOQ and ADIPOR1 and the CRC risk with a hospital-based case-control study in the Chinese population along with meta-analysis of available epidemiological studies.MethodsWith a hospital-based case-control study of 341 cases and 727 controls, the associations between the common variants on ADIPOQ (rs266729, rs822395, rs2241766 and rs1501299) and ADIPOR1 (rs1342387 and rs12733285) and CRC susceptibility were evaluated. Meta-analysis of the published epidemiological studies was performed to investigate the associations between the variants and CRC risk.ResultsFor the population study, we found that variant rs1342387 of ADIPOR1 was associated with a reduced risk for CRC [adjusted odds ratio (OR) = 0.74, 95% confidential intervals (95% CI) = 0.57-0.97; CT/TT vs. CC]. The meta-analysis also suggested a significant association for rs1342387 and CRC risk; the pooled OR was 0.79 (95% CI = 0.66-0.95) for the CT/TT carriers compared to CC homozygotes under the random-effects model (Q = 8.06, df = 4, P = 0.089; I2 = 50.4%). The case-control study found no significant association for variants rs266729, rs822395, rs2241766, and rs1501299 on ADIPOQ or variant rs12733285 on ADIPOR1 and CRC susceptibility, which were consistent with results from the meta-analysis studies.ConclusionsThese data suggested that variant rs1342387 on ADIPOR1 may be a novel CRC susceptibility factor.Electronic supplementary materialThe online version of this article (doi:10.1186/s12881-014-0137-y) contains supplementary material, which is available to authorized users.

AdipoQ T45G and G276T Polymorphisms and Susceptibility to Nonalcoholic Fatty Liver Disease Among Asian Populations: A Meta-Analysis and Meta-Regression.

Adiponectin (AdipoQ) is an adipose-derived plasma protein that plays an important role in hepatic lipoprotein-lipid metabolism. Emerging evidence have shown that two common polymorphisms (T45 G and G276 T) in the AdipoQ gene may contribute to increasing susceptibility to nonalcoholic fatty liver disease (NAFLD); however individually published studies show inconclusive results. This meta-analysis aimed to derive a more precise estimation of the association of AdipoQ T45 G (rs2241766 T>G) and G276 T (rs1501299 G>T) polymorphisms with NAFLD risk. Potential relevant studies were identified covering the following databases: PubMed, Embase, Web of Science, the Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), Chinese Bio-medicine Database (CBM), and Chinese Sci-tech Journals databases. Statistical analyses were calculated using the version 12.0 STATA software (Stata Corp, College Station, TX, USA). Odds ratios (ORs) and its corresponding 95% confidence interval (CI) were calculated. Ten case-control studies were included with a total of 2,672 subjects, of these 1,117 being NAFLD patients and 1,555 being healthy controls. Our meta-analysis results revealed that the T variant of AdipoQ rs2241766 T>G polymorphism may be associated with an increased risk of NAFLD. There was also a significant association between the G variant of AdipoQ rs1501299 G>T polymorphism and an increased risk of NAFLD. Country-stratified analysis indicated that a higher AdipoQ rs2241766 T>G polymorphism was closely related with an increased risk of NAFLD in Chinese and Indian populations (all Ps < 0.05); a similar result was observed in Chinese populations between AdipoQ rs2241766 T>G polymorphism and an increased risk of NAFLD (P < 0.05). In conclusion, the current meta-analysis indicates that AdipoQ rs2241766 T>G and rs1501299 G>T polymorphisms may contribute to an increasing susceptibility to NAFLD. Moreover, this meta-analysis also suggests for future larger studies with stratified case-control population, and greater focus on the gene-environment interactions regarding NAFLD susceptibility for valid studies.

Association study of the HTR2C, leptin and adiponectin genes and serum marker analyses in clozapine treated long-term patients with schizophrenia

Clozapine treatment is associated with weight gain and cardio-metabolic consequences among patients with schizophrenia. Polymorphisms of leptin, serotonin receptor HTR2C and adiponectin genes have been associated with antipsychotic-induced weight gain and metabolic comorbidity. However, the results of the studies so far are inconclusive. The aim of the present study was first to test for a possible role of serum leptin and adiponectin levels as a marker of weight gain in association with inflammatory cytokines/adipokines (IL-6, IL-1Ra, hs-CRP and adipsin), and second to study associations between SNPs LEP rs7799039 (-2548 A/G), ADIPOQ rs1501299 and HTR2C rs1414334 and weight gain and levels of leptin and adiponectin, in 190 patients with schizophrenia on clozapine treatment, with retrospectively assessed weight change and cross-sectionally measured cytokine levels. A strong association was found between serum levels of leptin and weight gain and cytokines/adipokines related to metabolic comorbidity, especially among female patients (in women leptin vs. weight gain, IL-6 and IL-1Ra, P<0.001; in men leptin vs. weight gain, P=0.026, leptin vs. IL-1Ra, P<0.001). In male patients low adiponectin level was a more specific marker of clozapine-induced weight gain (P=0.037). The results of the present study do not support a major role of SNPs LEP rs7799039, ADIPOQ rs1501299 and HTR2C rs1414334 in the regulation of weight gain or association of serum levels of leptin and adiponectin and corresponding studied SNPs in patients with schizophrenia on clozapine treatment.

Association of variants on ADIPOQ and AdipoR1 and the prognosis of gastric cancer patients after gastrectomy treatment.

Adiponectin is a protein hormone secreted exclusively by adipocytes and it is responsible for insulin sensitization in the human body. Deregulation of adiponectin and its downstream signaling pathway genes have been found to be involved in the gastric cancer carcinogenesis; however, whether the variants on adiponectin (ADIPOQ) and adiponectin receptor 1 (ADIPOR1) affect the prognosis of gastric cancer patients are still unknown. Here we have recruited 455 gastric cancer patients, who have received the gastrectomy treatment to evaluate the prognostic effects of variants on ADIPOQ (rs266729 and rs822395) and AdipoR1 (rs12733285 and rs1342387) for the gastric cancer patients. No significant association between the four variants and the overall survival of the gastric cancer patients was found. However, for those patients without a previous history of alcohol drinking, the rs266729 GG/CG genotype carriers showed a significantly decreased gastric cancer mortality compared to homogeneity CC patients (HR 0.74, 95 % CI 0.56-0.97; p = 0.032) after adjustment for variants age, sex, smoking status, tumor stage, tumor location and post-surgery chemotherapy. No significant association between the variant rs266729 genotypes and overall survival for the gastric cancer patients with an alcohol drinking habit. These data suggested that the variant rs266729 was an independent prognostic factor for the never drinking gastric cancer patients who received surgical treatment.

Association of variants in genes related to the immune response and obesity with BPH in CLUE II.

BACKGROUNDChronic inflammation and obesity may contribute to the genesis or progression of benign prostatic hyperplasia (BPH) and BPH-associated lower urinary tract symptoms (LUTS). The influence of variants in genes related to these states on BPH has not been studied extensively. Thus, we evaluated the association of 17 single nucleotide polymorphisms (SNPs) in immune response genes (IL1B, IL6, IL8, IL10, TNF, CRP, TLR4, RNASEL) and genes involved in obesity, including insulin regulation (LEP, ADIPOQ, PPARG, TCF7L2), with BPH.METHODSBPH cases (N=568) and age-frequency matched controls (N=568) were selected from among adult male CLUE II cohort participants who responded in 2000 to a mailed questionnaire. BPH was defined as BPH surgery, use of BPH medications, or symptomatic BPH (American Urological Association Symptom Index Score ≥15). Controls were men who had not had BPH surgery, did not use BPH medications, and whose symptom score was ≤7. Age-adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression.RESULTSNone of the candidate SNPs was statistically significantly associated with BPH. However, we could not rule out possible weak associations for CRP rs1205 (1082C>T), ADIPOQ rs1501299 (276C>A), PPARG rs1801282 (-49C>G), and TCF7L2 rs7903146 (47833T>C). After summing risk alleles, men with ≥4 had an increased BPH risk compared with those with ≤1 (OR, 1.78; 95% CI, 1.10-2.89; Ptrend=0.006).CONCLUSIONSNPs in genes related to immune response and obesity, especially in combination, may be associated with BPH.

Association of ADIPOQ polymorphisms with obesity risk: A meta-analysis

BackgroundThe association between ADIPOQ polymorphisms and the risk of obesity remains controversial. We perform a comprehensive meta-analysis to clarify the current understanding of this association. MethodsWe searched for relevant studies in PubMed, Embase and Cochrane library before February 2014. The strengths of the association between ADIPOQ polymorphisms and obesity risk were estimated by odds ratios (OR) with 95% confidence intervals (CI). ResultsEighteen case–control studies analyzing four SNPs (rs17300539, rs266729, rs1501299 and rs2241766) of ADIPOQ gene were eligible for the present meta-analysis. The pooling results showed that rs17300539 (2GG+GA vs. 2AA+GA: OR=0.78, 95%CI=0.69–0.89) and rs1501299 (2GG+GA vs. 2AA+GA: OR=0.89, 95%CI=0.80–0.98) were associated with obesity risk in Caucasian ethnicity. The rs266729 were associated with obesity risk in Asian ethnicity (2CC+CG vs. 2GG+GCG: OR=0.77, 95%CI=0.65–0.92). However, there were no associations between rs2241766 and the obesity risk (P>0.05). No publication bias was found among these studies (all P>0.05). ConclusionsThis study suggests that ADIPOQ rs17300539 and rs1501299 are associated with risk of obesity in Caucasian ethnicity, and the rs266729 is associated with obesity risk in Asian ethnicity. However, there is no association between rs2241766 and obesity risk.

Five Common Haplotype-Tagging Variants of Adiponectin (ADIPOQ) and Cancer Susceptibility: A Meta-Analysis

The relationship between common haplotype-tagging polymorphisms (rs266729 [11365C>G], rs822395 [-4034A>C], rs822396 [-3964A>G], rs2241766 [45T>G], and rs1501299 [276G>T]) in the ADIPOQ gene and cancer risk has been investigated in different ethnic groups; however, these studies have yielded contradictory results. With this in mind, this meta-analysis was performed in an attempt to draw a more precise conclusion regarding the association between ADIPOQ polymorphisms and cancer risk. In this study, with a total of 19 eligible articles consisting of 52 studies, the pooled odds ratios (ORs) for the association between ADIPOQ rs1501299 and cancer risk were statistically significant (dominant model, TT/GT vs. GG, OR=0.84, 95% confidence interval [CI]: 0.77-0.92; homozygous model, TT vs. GG, OR=0.80, 95% CI: 0.68-0.94). These results suggested that ADIPOQ rs1501299 might be a protection-associated polymorphism in cancer. The stratified analyses indicated that the variant T allele of ADIPOQ rs1501299 was associated with decreased risk of cancer in both Caucasian and Asian populations when compared with the G allele. No significant association for the rest of the polymorphisms was observed under any genetic model. This meta-analysis suggests that the ADIPOQ rs1501299 may be a protective factor for carcinogenesis.

Association of adiponectin (ADIPOQ) rs2241766 polymorphism and dyslipidemia in HIV/HCV‐coinfected patients

The adiponectin (ADIPOQ) rs2241766 polymorphism is related to metabolic abnormalities. The aim of this study was to evaluate the association of the ADIPOQ rs2241766 polymorphism with serum dyslipidemia and insulin resistance (IR) in human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients. We carried out a cross-sectional study on 262 patients. ADIPOQ rs2241766 polymorphisms were genotyped by GoldenGate® assay. Generalized linear models (GLMs) were used to compare continuous outcome variables (total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL-C and homeostatic model assessment (HOMA)) and categorical outcome variables (TC≥200 mg/dL, TG≥170 mg/dL, LDL-C≥100 mg/dL, HDL-C≤35 mg/dL, non-HDL-C≥120 mg/dL and HOMA≥3·8) according to ADIPOQ genotype under a dominant inheritance model. Patients with the rs2241766 GG/GT genotype had significantly lower serum TC levels (P=0·038) and percentages of TC≥200 mg/dL (P=0·022) than rs2241766 TT carriers. When adjusted GLM was performed, rs2241766 GG/GT was associated with low serum TC levels (arithmetic mean ratio (AMR)=0·92 [(95% CI=0·85; 0·99) P=0·024]) and low likelihood of TC≥200 mg/dL (odds ratio (OR)=0·32 [(95% CI=0·11; 0·88) P=0·027]. When stratifying by steatosis, no significant values were found for patients without steatosis. However, for patients with steatosis, rs2241766 GG/GT genotypes were related to low TC serum values of TC (AMR=0·89; P=0·027), LDL-C (AMR=0·85; P=0·039) and non-HDL-C (AMR=0·86; P=0·015). No significant associations were found between rs2241766 and HOMA values. The presence of the ADIPOQ rs2241766 G allele (GG/GT genotype) was associated with a protective effect against dyslipidemia, primarily in HIV/HCV-coinfected patients with steatosis.

Genetic variations of the ADIPOQgene and risk of prostate cancer in Chinese Han men.

Adiponectin secreted by adipose tissue has been implicated in prostate carcinogenesis. Genetic variations in ADIPOQ are thought to influence the activity of adiponectin, thus relating to cancer occurrence. In this hospital-based case-control study of 917 prostate cancer (PCa) cases and 1036 cancer-free controls, we evaluated the association of single nucleotide polymorphisms in ADIPOQ with risk of PCa and adiponectin levels in Chinese Han men. Variants of ADIPOQ were genotyped by Taqman polymerase chain reaction method. The plasma adiponectin concentrations were measured by enzyme-linked immunosorbent assay (ELISA) in a subset of cases and controls. We found that the ADIPOQ rs3774262 variant AA genotype was associated with both decreased PCa risk [adjusted odds ratio (OR): 0.66, 95% confidence interval (CI) =0.48–0.92] and increased plasma adiponectin levels (P = 0.036 and 0.043), with significant difference by tumor grade, clinical stage, and aggressiveness. A significant interaction between ADIPOQ rs3774262 and body mass index was observed in modifying the risk of PCa (P = 6.7 × 10−3). ADIPOQ rs266729 and rs182052 were not related to PCa risk or plasma adiponectin levels. Our data support that ADIPOQ rs3774262 may affect PCa risk in combination with plasma adiponectin levels in Chinese Han men. It may contribute to the molecular basis for the association between obesity and PCa.

Case-control study of diabetes-related genetic variants and pancreatic cancer risk in Japan.

To examine whether diabetes-related genetic variants are associated with pancreatic cancer risk. We genotyped 7 single-nucleotide polymorphisms (SNPs) in PPARG2 (rs1801282), ADIPOQ (rs1501299), ADRB3 (rs4994), KCNQ1 (rs2237895), KCNJ11 (rs5219), TCF7L2 (rs7903146), and CDKAL1 (rs2206734), and examined their associations with pancreatic cancer risk in a multi-institute case-control study including 360 cases and 400 controls in Japan. A self-administered questionnaire was used to collect detailed information on lifestyle factors. Genotyping was performed using Fluidigm SNPtype assays. Unconditional logistic regression methods were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between these diabetes-associated variants and pancreatic cancer risk. With the exception of rs1501299 in the ADIPOQ gene (P = 0.09), no apparent differences in genotype frequencies were observed between cases and controls. Rs1501299 in the ADPIOQ gene was positively associated with pancreatic cancer risk; compared with individuals with the AA genotype, the age- and sex-adjusted OR was 1.79 (95%CI: 0.98-3.25) among those with the AC genotype and 1.86 (95%CI: 1.03-3.38) among those with the CC genotype. The ORs remained similar after additional adjustment for body mass index and cigarette smoking. In contrast, rs2237895 in the KCNQ1 gene was inversely related to pancreatic cancer risk, with a multivariable-adjusted OR of 0.62 (0.37-1.04) among individuals with the CC genotype compared with the AA genotype. No significant associations were noted for other 5 SNPs. Our case-control study indicates that rs1501299 in the ADIPOQ gene may be associated with pancreatic cancer risk. These findings should be replicated in additional studies.

An updated meta-analysis of the association between ADIPOQ rs2241766 polymorphism and colorectal cancer

Adiponectin (ADIPOQ) is a cytokine produced by adipose tissue involved in carcinogenesis. ADIPOQ SNP rs2241766 has been extensively studied in colorectal cancer (CRC) community with contentious and conflicting conclusions. The objective of this study was to comprehensively assess the association between SNP rs2241766 and CRC risk. PubMed, Embase, CNKI, as well as the references of the retrieved articles were searched to identify the eligible studies for this meta-analysis. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the association. We also examined the heterogeneity and publication bias and performed sensitivity analyses. Seven studies with 2,414 cases and 2,796 controls together did not show any significant association between SNP rs2241766 and CRC risk. Subgroup analyses by ethnicity and sample size also failed to provide statistically significant evidence. This meta-analysis demonstrates that ADIPOQ SNP rs2241766 may not represent as an effect modifier for the risk of CRC.

Gene Polymorphisms of ADIPOQ +45T&gt;G, UCP2 -866G&gt;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 Pmulti = 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 (Ptrend = 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.

The adiponectin gene single-nucleotide polymorphism rs1501299 is associated with hepatocellular carcinoma risk

Increasing lines of evidence have suggested that adiponectin, an adipocyte-derived hormone, plays an important role in the development of hepatocellular carcinoma (HCC). However, the relationship between genetic variants of the adiponectin gene (ADIPOQ) and HCC has not been previously explored. Therefore, we performed a case-control study to examine the association of haplotype-tagging single-nucleotide polymorphisms (SNPs) in ADIPOQ with HCC risk. Five haplotype-tagging SNPs of ADIPOQ (rs266729, rs822395, rs822396, rs2241766 and rs1501299) were genotyped in 200 HCC patients and 200 non-HCC controls by PCR amplification and direct sequencing. Logistic regression was used to estimate the risk of HCC associated with each individual SNP and we adjusted for multiple testing by the Bonferroni correction. Of the five tested SNPs, rs1501299 showed a strong and significant association with HCC risk even after the Bonferroni correction. After adjusting for the serological status of the hepatitis virus B core antibody and for other SNPs, the odds ratios were 4.33 [95 % confidence interval (CI) 2.07-9.05; corrected P < 0.005] and 3.71 (95 % CI 1.84-7.48; corrected P < 0.005) for the GG genotype and GG/GT combined genotype, respectively, versus the TT genotype. This is the first report, demonstrating an association of ADIPOQ polymorphisms with HCC risk. Our results implicate the ADIPOQ SNP rs1501299 as a susceptibility locus for HCC.

Abstract 116: Association between variation in LEP A19G and adipokine concentrations in plasma and breast tissues.

Abstract Introduction: Obesity is a well-established postmenopausal breast cancer risk factor, and an indicator of poor prognosis. The adipokines, adiponectin and leptin, may be essential to our understanding these associations. Plasma concentrations of adiponectin are inversely correlated, while plasma concentrations of leptin are positively correlated with obesity. Epidemiological studies of these adipokines and breast cancer risk are suggestive of a positive association for plasma leptin and an inverse association for plasma adiponectin. We studied whether genetic variation in several adipokine genes, leptin (LEP), leptin receptor (LEPR), adiponectin (ADIPOQ), and adiponectin receptors 1 and 2 (ADIPOR1/2) was associated with adipokine concentrations measured in plasma and breast tissue in a study of healthy women. Methods: Breast tissues and plasma were collected from 85 women undergoing reduction mammoplasty between 1997 and 2009. Plasma and breast adiponectin and leptin concentrations were measured by commercially-available ELISA kits. DNA was extracted from dissected breast tissues and common, functional SNPs in LEP (rs2167270), LEPR (rs1137101), ADIPOQ (rs1501299), ADIPOR1 (rs2275737), and ADIPOR2 (rs1044471) were genotyped. Differences in least-squares mean concentration of plasma and breast adipokines, adjusted for age, race, and body mass index (kg/m2), were compared using an F test. Associations between genotypes and adipokines measured in plasma and tissue were estimated using adjusted regression models, with log-transformed adipokines as dependent variables. Results for each genotype are given as eβ, representing the ratio of plasma adipokines among those carrying a variant genotype relative to those carrying the wild-type. Results: Genotype of rs2167270 was significantly associated with plasma adiponectin and leptin, and breast leptin concentrations. Compared to the wild-type, homozygous variant allele carriers of the LEP A19G polymorphism had 27% lower plasma adiponectin (Ratio 0.73, 95% CI: 0.54, 0.98; P=0.03) and plasma leptin (Ratio 0.73, 95% CI: 0.55, 0.96; P=0.02). Additionally, compared to wild-type, heterozygous variant allele carriers of this polymorphism had 39% lower breast leptin (Ratio 0.61, 95% CI: 0.39, 0.97; P=0.03), although there appeared to be higher breast leptin among homozygous variant allele carriers (Ratio 1.67, 95% CI: 0.86, 3.26). No associations were observed for LEPR (rs1137101), ADIPOQ (rs1501299), ADIPOR1 (rs2275737), or ADIPOR2 (rs1044471) and adipokines measured in plasma or tissue. Conclusion: Variant alleles of rs2167270 were associated with lower plasma adiponectin and leptin concentrations, as well as lower breast leptin concentrations. This study provides evidence for a role of variation in adipokine genes in endogenous adipokine concentrations both in circulation and within local breast tissues. Citation Format: Adana A. Llanos, Theodore M. Brasky, Kepher H. Makambi, Jo L. Freudenheim, Peter G. Shields. Association between variation in LEP A19G and adipokine concentrations in plasma and breast tissues. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 116. doi:10.1158/1538-7445.AM2013-116