ADIPOQ Rs1501299 Research Articles

1330-P: Molecular Biomarkers during Gestational Diabetes Mellitus

Background/Aim: Gestational diabetes mellitus (GDM) is associated with short- and long-term complication in both mothers and offspring. Molecular mechanisms are attracting increased interest for their potential as biomarkers for GDM that could lead to improved detection of GDM with positive effects on health outcomes. The aim of this study was to explore the potential of DNA methylation and single nucleotide polymorphisms (SNPs) to serve as molecular biomarkers for GDM in South African women. Methods: Genome-wide DNA methylation using a MethylationEPIC BeadChip Array (n=24) and gene-specific methylation of the adiponectin (ADIPOQ) gene using bisulfite pyrosequencing (n=286) were profiled in the peripheral blood of women with or without GDM. In addition, variants ADIPOQ rs266729 and rs17300539, and methylenetetrahydrofolate reductase (MTHFR) rs1801133 were quantified using quantitative real-time PCR (n=449). Results: Genome-wide methylation analysis identified 1046 differentially methylated CpG sites (associated with 939 genes), of which 148 CpG sites were hypermethylated and 898 CpG sites were hypomethylated (p<0.01). Among the top five CpG sites, one CpG mapped to the calmodulin-binding transcription activator 1 (CAMTA1) gene, which has been shown to regulate insulin production and secretion. Two CpG sites (-3410: p=0.048 and -3400: p=0.004) in the ADIPOQ promoter were hypomethylated during GDM in Human Immunodeficiency Virus (HIV) negative, but not in HIV positive women. Lastly, no association between ADIPOQ and MTHFR polymorphisms and GDM was observed in our population. Discussion: DNA methylation may offer potential as molecular biomarkers for GDM in a South African population. Future longitudinal studies in larger samples that include both HIV negative and positive pregnant women are warranted to explore the candidacy of DNA methylation as molecular biomarkers for GDM. Disclosure S. Dias: None. S. Adam: None. P. Rheeder: None. J. Louw: None. C. Pheiffer: None. Funding National Research Foundation (99391); South African Medical Research Council

The association of Adiponectin polymorphism (rs2241766) with susceptibility and prognosis in Egyptian Hematological malignancies Patients: A case–control study

Background: Haematological malignancies are ranked as the highest in incidence. Adiponectin (ADIPOQ), the most abundant circulating adipocytokine, plays a major role in the regulation of insulin sensitivity, metabolism, and hematopoiesis. Various ADIPOQ gene polymorphisms are associated with an increased risk of different cancers. However, to the best of our knowledge, the association between ADIPOQ T45G (rs2241766) single nucleotide polymorphism (SNP) and leukemia is unknown. Aim: This study aimed to investigate the association between ADIPOQ (rs2241766) and the clinicopathological status of Egyptian leukemia patients. Materials and Methods: A case-control design was used, including 80 leukemia patients and 70 healthy controls. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used for genotyping. Survival analysis and biochemical investigations including hematological and lipid profiles, liver and kidney functions in addition to anthropometric measurements were also determined. Results: A significant positive correlation between ADIPOQ gene T45G (rs2241766) SNP and leukemia incidence was detected. The G allele was more frequent in leukemia patients compared to the T allele. Kaplan-Meier analysis revealed that the SNP rs2241766was associated with the patient’s event-free survival but not the overall survival. In addition, G carriers, hyperglycemia, and hyperuricemia patients had a significantly shorter median EFS compared with T carriers, normoglycaemia, and normoglycemia patients. Conclusion: The current study shows an association between the SNP (rs2241766) and leukemia incidence and prognosis in Egyptian patients. Furthermore, an association between the rs2241766 and high prevalence of hyperglycemia and dyslipidemia in the G allele carrier’s leukemia patients was also evident.

Protective Association of Single Nucleotide Polymorphisms rs1861868-FTO and rs7975232-VDR and Obesity in Saudi Females.

BackgroundObesity is a major health threat worldwide. It predisposes individuals to diabetes, cardiovascular complications, and cancer. Genetic and environmental factors are responsible for the increasing incidence of obesity. In this study, we investigated the genetic factors associated with obesity in young Saudi women.Subjects and MethodsIn this cross-sectional study, 131 young Saudi female students were recruited. Body mass index (BMI), waist–hip ratio, blood glucose, triglyceride, cholesterol, HDL, LDL, and vitamin D3 levels of the subjects were determined. Twelve SNPs of different genes that showed a correlation with obesity in different population were tested, namely GNPDA2 (rs10938397), TCF7L2 (rs10885409), FTO (rs1477196), ADIPOQ (rs1501299), MC4R (rs17782313), ABCA1 (rs1800977), FTO (rs1861868), VDR (rs2228570), VDR (rs731236), VDR (rs7975232), ADIPOQ (rs266729), and PFPK (rs6602024). Student’s t-test was conducted for all parameters. Pearson correlation was performed to identify the correlated variables. The frequencies of different risk alleles were determined by direct counting of the test allele divided by the total number of alleles and compared.ResultsOnly two SNPs, rs1861868 of FTO and rs7975232 of VDR, of the twelve tested SNPs showed significant protective associations with the BMI with odds ratio 0.3886 (0.1761–0.8572); p 0.0192 and odds ratio 0.4563 (0.2343–0.8888); p 0.0211, respectively.ConclusionThe current study showed that minor alleles, “T” of FTO and “A” of VDR, might be protective factors against increased BMI in young Saudi female subjects. To elucidate this association, further studies with larger sample size involving both sexes are required.

The Association between Adiponectin Single Nucleotide Polymorphisms and Side Effects of Isotretinoin in Acne Patients.

Background Acne is a common condition of pilosebaceous follicle especially among young. Clinically, the most used medication in the treatment of moderate to severe acne is oral isotretinoin. However, interindividual variability in therapeutic response to isotretinoin and many side effects such as musculoskeletal pain, headache, and alteration in lipid profile can be seen with this treatment. Aim In this study, the effect of genetic polymorphisms, rs2241766 and rs1501299, of the adiponectin gene was investigated in relation to the side effects of isotretinoin-treated young adult acne patients (n = 230). Methods Several biochemical parameters were measured at baseline and after treatments with isotretinoin. The ADIPOQ gene SNPs, rs2241766 and rs1501299, were genotyped in 230 patients. Results Alterations in lipid profile with a significant increase of ALT (P=0.007) were detected after isotretinoin treatment. Moreover, percentage change in HDL following isotretinoin treatment was significantly associated with rs1501299 (P=0.008). On the other hand, no associations between examined SNPs and side effects of isotretinoin and other lipid parameters (total cholesterol, LDL, and triglycerides) or liver function enzymes (ALT and AST) were detected. Conclusions Current findings showed that rs1501299 of the ADIPOQ gene might be associated with changes in HDL level in acne patients following treatment with isotretinoin.

Association of Adiponectin Genotypes With Colorectal Cancer Susceptibility in Taiwan.

To investigate the association between adiponectin (ADIPOQ) genotypes and colorectal cancer (CRC) risk among Taiwanese. Polymerase chain reaction-restriction fragment length polymorphism was adopted to identify ADIPOQ rs266729, rs2241766 and rs1501299 genotypes among 362 CRC patients and 362 healthy controls. ADIPOQ rs266729 GG genotype (p=0.0075) and G allele (p=0.0061) are associated with a significantly increased CRC risk. There is no differential distribution of rs2241766 and rs1501299 genotypes. As for the gene-lifestyle interaction, there are obvious joint effects of rs266729 genotype on the CRC risk among non-smoker, non-alcohol drinker, while not on smoker or non-drinker subgroups. No significant correlation was observed between rs266729 genotypic distributions and age, gender, tumor size, location or metastasis status. Interestingly, a correlation of rs266729 genotype and larger BMI on CRC risk was found. G allele at ADIPOQ rs266729 may serve as a determiner for CRC risk, especially for those with BMI ≥24.

Association of polymorphisms in leptin and adiponectin genes with long-term outcomes in renal transplant recipients.

The effect of polymorphims in leptin and adiponectin genes on long-term outcomes of renal transplantation is unknown. In 349 renal transplant recipients (RTR), we aimed to determine associations between five SNPs in the leptin receptor (LEPR) and adiponectin (ADIPOQ) genes and these outcomes. Follow-up time ranged from 2 to 25 years (mean 10.29 ± 5.16 years). Two SNPs showed associations with long-term outcomes and their statistical significance greatly increased after 39 RTR with a history of cardiovascular events prior to transplantation were removed from the analysis. Adjusted odds ratios (OR) for LEPR rs1805094 and ADIPOQ rs1501299 and risk of graft loss were 0.35 (0.16-0.74) p = 0.006 and 2.37 (1.28-4.37) p = 0.006, respectively. The assessment of risk for global mortality revealed OR values of 0.20 (0.06-0.62), p = 0.005, and 2.43 (1.08-5.44), p = 0.031 for LEPR rs1805094 and ADIPOQ rs1501299, respectively. Our results show that polymorphism in genes involved in leptin and adiponectin function modify long-term outcomes in renal transplantation.

Association study of the single-nucleotide polymorphisms -3971G/A and +276G/T in the adiponectin gene with type 2 diabetes in a North Indian Punjabi population.

To investigate the role of ADIPOQ gene variants (-3971G/A rs822396 and +276G/T rs1501299) with type 2 diabetes risk in a North Indian Punjabi population. Adiponectin is one of the most abundant circulating adipocytokines in the human body that plays an important role in the metabolic processes and positively regulates energy homeostasis and insulin secretion. Several studies have provided the evidence of adiponectin gene polymorphisms association with type 2 diabetes mellitus (T2DM) in different ethnic populations. A total of 616 subjects including 316 T2DM patients and 300 normal healthy controls from Punjab were genotyped for ADIPOQ polymorphisms (rs822396 and rs1501299) by using a polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) technique. Anthropometric, physiometric, and biochemical measurements were taken from each participant. Genotypic frequencies were significantly different in T2DM subjects and healthy controls for both polymorphisms (rs822396 and rs1501299). The risk genotype GG of -3971A/G and TT of +276G/T conferred an approximately twofold risk towards the development of T2DM and were found to be significantly higher in T2DM cases than control subjects (p = 0.006 and p = 0.019, respectively, after the Bonferroni correction). The recessive model of the ADIPOQ polymorphism rs822396 was significantly shown to confer a 3.63-fold risk towards type 2 diabetes after adjusting for confounding factors and Bonferroni correction [odds ratio (OR): 3.63 (1.20-10.96), p = 0.022]. rs1501299 gave a 3.82-fold risk towards development of T2DM but was not statistically significant after Bonferroni correction [OR: 3.82 (1.16-12.55), p = 0.027]. Meta-analysis also illustrated the overall effect of the minor allele of rs822396 (-3971A/G) polymorphism, providing a greater risk for the T2DM development. Thus, we concluded on the basis of observed results that the ADIPOQ gene polymorphisms rs822396 and rs1501299 plays an important role in the development of type 2 diabetes in North Indian Punjabi population.

Risk of Wnt/β-catenin signalling pathway gene polymorphisms in primary Sjögren's syndrome.

To explore genetic polymorphisms of the Wnt/β-catenin signalling pathway in primary SS (PSS). We included 98 patients with PSS and 165 healthy volunteers. Genomic DNA was extracted from peripheral blood samples. Through an open-array platform of low density, we genotyped 25 polymorphisms from 14 genes (WISP1, DKK1, SOST, FRZB, LRP1, LRP4, LRP5, LRP6, GSKB, ADAMTS5, GDF5, FMN2, ADIPOQ and COL11A1) involved in the Wnt/β-catenin signalling pathway. We compared the allelic and genotypic frequencies with Fisher's exact test and logistic regression analysis adjusted by age, gender and individual admixture, as well as bootstrap-resampling analysis. We assessed the gene-gene interaction by the multifactor dimensionality reduction method. We found a positive significant association with four polymorphisms: LRP5 rs606989, FRZB rs409238, GSK3B rs2037547 and ADIPOQ rs2241766. All of them conferred risk for PSS, being the highest among subjects carrying three to four risk alleles (P < 0.001). According to a multifactor dimensionality reduction analysis, the best models included the LRP5 (rs606989), FRZB (rs409238) and ADIPOQ (rs2241766) polymorphisms. LRP5, FRZB and ADIPOQ genes related in the Wnt/β-catenin signalling pathway increased the risk of PSS. Further research is needed to establish their functional role in this clinical entity.

Common Type 2 Diabetes Genetic Risk Variants Improve the Prediction of Gestational Diabetes.

Gestational diabetes mellitus (GDM) is a carbohydrate intolerance that occurs in women during pregnancy. The aims of this study were to develop a model to predict the risk of GDM development using common clinical parameters and selected genetic polymorphisms and to analyse the performance of the model using receiver operator characteristic (ROC) curves. ROC analysis was used to examine whether the evaluation of genetic polymorphisms may enhance the accuracy of GDM prediction in comparison to using common clinical risk factors only. This study included 204 pregnant women with GDM and 207 pregnant women with normal glucose tolerance. The diagnosis of GDM was based on a 75 g oral glucose tolerance test at 24-28 weeks gestation. The difference between the AUC of ROC curves for the model 1 including only age and BMI and the model 2 also including 8 genetic polymorphisms was highly significant (p=0.0001) in favour of model 2 (0.090±0.023). Moreover, the additional use of 8 genetic polymorphisms may increase both the sensitivity and specificity of GDM prediction by 10%. The results of this study indicate that the use of 8 genetic polymorphisms associated with carbohydrate and lipid metabolism and type 2 diabetes [PTGS2 (COX2) rs6681231, FADS1 rs174550, HNF1B rs4430796, ADIPOQ rs266729, IL18 rs187238, CCL2 rs1024611, HHEX rs5015480 and CDKN2A/2B rs10811661] together with clinical risk factors (BMI and age) may significantly improve the prediction of GDM.

Adiponectin rs2241766 and rs266729 gene polymorphisms in non-alcoholic fatty liver disease

BackgroundIn this study, we aimed to examine the association of adiponectin (ADIPOQ) rs2241766 (+45T/G) and rs266729 (−11377C/G) gene polymorphisms with serum ADIPOQ in non-alcoholic fatty liver disease (NAFLD). MethodsADIPOQ rs2241766 and rs266729gene polymorphisms were genotyped by using TaqMan 5′-nuclease assay and serum ADIPOQ level was measured in 100 NAFLD patients and 100 healthy controls. ResultsThe study revealed an association of G- allele of ADIPOQ rs2241766 gene polymorphism with NAFLD; X2 (P-value); 3.95 (0.047). Moreover, G-allele of ADIPOQ rs266729 gene polymorphism increased significantly in the patients compared to controls, X2 (P-value): 3.9 (0.046). The study also revealed lower serum ADIPOQ levels in NAFLD patients compared to controls (P < 0.001). There was no association between ADIPOQ rs266729 and rs2241766 gene variants and serum ADIPOQ levels in the participants. In NAFLD patients, Low serum ADIPOQ was associated with elevated liver enzymes and altered lipid profile values. ConclusionG-alleles of rs2241766 (+45 T/G) and rs266729 (−11377C/G) gene polymorphisms of ADIPOQ gene were associated with NAFLD, but not with serum ADIPOQ levels.

Epistasis between ADIPOQ rs1501299 and PON1 rs662 polymorphisms is potentially associated with the development of knee osteoarthritis.

Overweight produces oxidative stress (OS) on the articular cartilage, with the subsequent risk of developing knee osteoarthritis (OA). Associations between genetic polymorphisms related to OS and OA have been reported, but it is currently unknown whether there exist interactions among them that affect OA development. To identify and evaluate interactions between multiple SNPs related to OS in Mexican knee OA patients. Ninety-two knee OA patients were included in the study, which were compared to 147 healthy controls. Nine variants of six genes (PEPD, AGER, IL6, ADIPOQ, PON1, and CA6) related to OS were genotyped in both study groups through the OpenArray system. Epistasis was analyzed with the multifactor dimensionality reduction (MDR) method. The MDR analysis revealed a significant interaction (p = 0.0107) between polymorphisms rs1501299 (ADIPOQ) and rs662 (PON1), with an entropy value of 9.84%; in addition, high and low risk genotypes were identified between these two polymorphisms. The effect of the interaction between rs1501299 (ADIPOQ) and rs662 (PON1) polymorphisms seems to play an important role in OA pathogenesis; so the epistasis analysis may provide an excellent tool for identifying individuals at high risk for developing OA.

Synergism of Adipocytokine Profile and ADIPOQ/TNF-α Polymorphisms in NAFLD-associated MetS Predict Colorectal Liver Metastases Outgrowth.

The aim of this study was to evaluate whether the altered profile of adipocytokine and genetic fingerprint in NAFLD-associated metabolic syndrome "cluster" represents synergistic risk factors predicting onset of liver colorectal cancer metastases. A total of 165 colorectal cancer patients were enrolled, 56,3% were with metabolic syndrome/NAFLD. Serum samples were assayed for ADIPOQ, leptin and TNF-a levels by ELISA. ADIPOQ rs266729 C/G and TNF-308 A/G genotypes were analyzed in DNA isolated from whole blood. Reduction in adiponectin levels and increase in leptin and TNF-α was shown in patients with liver metastases. This trend was influenced by BMI, MetS/NAFLD, and insulin resistance. ADIPOQ G rs266729 and TNF- 308 A allele are associated with obesity, MetS/NAFLD and insulin resistance. ADIPOQ CG/GG and GA/AA TNF-alpha genotypes confer susceptibility to liver metastases. Obesity and hepatic steatosis significantly favor the development of colorectal cancer liver metastases and the individual adipocytokines genetic profile may play an important predictive role.

Adipokine gene variability and plasma levels in patients with chronic periodontitis -a case-control study.

Specific variants in genes that encode adipokines and their mRNA and protein expression were previously studied in type 2 diabetes mellitus (T2DM) and obesity, and similar studies have been performed for chronic periodontitis (CP). The aim of this case-control study was to investigate the possible impacts of adiponectin (ADIPOQ), leptin (LEP) and its receptor (LEPR), and resistin (RETN) on the etiopathogenesis of CP. Examinations were performed on 118 non-periodontitis healthy subjects (healthy controls, HC), 205 healthy individuals with CP (H + CP) and 86 type 2 diabetes patients with CP (T2DM + CP). Variants within the ADIPOQ (rs2241766, rs1501299), LEP (rs13228377, rs2167270), LEP receptor (rs1805096), and RETN (rs1862513) genes were determined by qPCR. In addition, the plasma levels of ADIPOQ, LEP, and RETN were analysed by ELISA for 80 individuals. The genotype frequencies of the SNP ADIPOQ +45G/T (rs2241766) differed between the HC and H + CP groups (p=0.03, pcorr>0.05), and carriers of the TT genotype had a lower risk of developing CP compared to carriers of the GG or TG genotypes (p<0.01, pcorr>0.05). However, there were no significant differences in the plasma levels of ADIPOQ, LEP or RETN between the study groups (p > 0.05). Plasma levels of the adipokines were also independent of the gene profiles (p > 0.05). Adipokine plasma levels did not change in patients with H + CP/T2DM + CP compared to HC, but we did identify a specific polymorphism in the ADIPOQ gene that was associated with CP. Although the ADIPOQ +45G/T (rs2241766) gene variant may be a candidate biomarker for CP, further research is required in larger populations with different ethnic backgrounds before any final conclusions can be drawn about the role of this gene in CP.

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.

Investigation of potential genomic biomarkers for obesity and personalized medicine

Obesity, as a global health issue, is a complex metabolic syndrome and its association with many chronic diseases. The pathology of obesity results from an interaction of psychological, environmental and variety of genetic factors. Etiologic determinants and molecular pathophysiology of obesity have not yet understood clearly. Previously shown that genetic markers have a significant role in the development of obesity, although results are divergent with populations. Turkish Cypriots have a unique mixture of allele distributions as being a small-islander population. Therefore, the current study was aimed to evaluate the association between obesity and three putative obesity-related ADIPOQ, FTO and ACE gene markers, respectively. We investigated a possible association of ADIPOQ rs2241766 G>T, FTO rs9939609 A>T and ACE rs4340288 DIP variants among obese and non-obese Turkish Cypriot origin. Additionally, the correlation between these variants and biochemical and physical measurements were also evaluated to determine the possible biomarker for obesity in the population. Only FTO rs9939609 A>T polymorphism was associated with obesity and no association was observed with ADIPOQ rs2441666 G>T and ACE rs4340288 DIP. To conclude, FTO rs9939609 A allele found to have strong association with obesity in the population of Turkish Cypriots.

Genetic association of ADIPOQ gene variants (-3971A>G and +276G>T) with obesity and metabolic syndrome in North Indian Punjabi population.

Background and aimsAt present obesity and metabolic syndrome (MetS) in India are the most challenging health problems. It is also well accepted that obesity is a significant risk factor for the development of metabolic syndrome and other degenerative diseases. Many studies have reported that single-nucleotide polymorphisms (SNPs) of the adiponectin (ADIPOQ) gene have been associated with obesity and its related disorders. Here, we aimed to investigate the association of two intronic variants in ADIPOQ gene, -3971A>G (rs822396) and +276G>T (rs1501299) with obesity and metabolic syndrome.MethodsBiochemical and anthropometric measurements were obtained from a total of 550 unrelated subjects (obese = 250 and non-obese = 300) of North Indian Punjabi population. Genotyping for the intron variants were performed by polymerase chain reaction based restriction fragment length polymorphism (PCR-RFLP) methods. After genotyping, as a quality control measure 10% of the samples for each polymorphism were confirmed by Sanger Sequencing method. The distributions of genotypic and allelic frequencies among obese and non-obese groups were compared by chi-square test and the corresponding risk was calculated using binary logistic regression. The effects of multiple testing were controlled by applying Bonferroni corrections.ResultsAll the anthropometric and biochemical parameters except triglycerides (TG) and very low-density lipoproteins cholesterol (VLDL-C) have shown significant association with both GG and TT genotypes of -3971A>G (rs822396) and +276G>T (rs1501299) polymorphisms respectively. The frequencies of GG (-3971A>G) and TT (+276G>T) genotypes were higher among obese cases (p = 0.008 and p = 0.035 respectively). However, no significant association was found between allelic frequencies of ADIPOQ rs822396 and obesity, whereas the association of ADIPOQ rs1501299 attenuated and became marginally significant after Bonferroni correction (p>0.025). Both the variant genotypes of ADIPOQ gene polymorphisms (-3971GG and +276TT) significantly increased the risk of development of obesity (OR: 1.52, p = 0.03; OR: 1.58, p = 0.04 respectively) and MetS (OR: 1.42, p = 0.03; OR: 1.57, p = 0.01 respectively) in the present population, after adjusting the various covariates. The G-T haplotype model (possessing -3971G and +276T alleles) was shown toprovide ~ 3 fold risk towards the obesity susceptibility (OR: 2.69, p = 0.009) and MetS risk (OR: 2.73, p = 0.009) and the association persisted after adjusting for different confounding variables.ConclusionThe present study has confirmed that ADIPOQ -3971A>G (rs822396) and +276G>T (rs1501299) polymorphism may be clinically helpful to estimate obesity and MetS risk in North Indian Punjabi population.

Genetic susceptibility to pre diabetes mellitus and related association with obesity and physical fitness components in Mexican-Mestizos

Pre diabetes mellitus (pre-DM) is considered an early-reversible condition that can progress to Type 2 diabetes mellitus (T2DM) which is the main cause of death for adult Mexican population. Gene variants influencing fasting glucose levels may constitute helpful tool for prevention purposes in pre-DM condition. Physically active Mexican-Mestizo adults (n=565) were genotyped for 6 single nucleotide polymorphisms (SNPs) (ADIPOQ rs2241766, ACSL1 rs9997745, LIPC rs1800588, PPARA rs1800206, PPARG rs1801282 and PPARGC1A rs8192678) related to lipid and carbohydrate metabolism. Fasting glucose was measured and values classified as pre-DM (≥100mg/dL) or normal fasting glucose. Logistic models were used to test associations between pre-DM condition and SNPs, and interaction with Body Mass Index (BMI) and physical fitness components. The A allele of ASCL1 rs9997745 conferred increased risk (OR=3.39, p=0.001) of pre-DM which is modulated by BMI. The A allele of the PPARGC1A rs8192678 showed significant SNP*BMI (OR=1.10, p=0.008) interaction effect for pre-DM risk, meaning that obese subjects showed higher pre-DM risk but normal weight subjects showed lower risk. The effect increased with age and was attenuated by higher cardiorespiratory values. We found that both ACSL1 rs9997745 and PPARGC1A rs8192678 are associated with pre-DM, and that BMI significantly modified their association.

T allele at ADIPOQ rs1501299 G/T polymorphism is more susceptible to the influence of circulating adiponectin on arterial stiffness in nondiabetic men

BackgroundLow adiponectin levels are associated with increased insulin resistance (IR) and arterial stiffness in hypertensive patients, but higher adiponectin levels are also found in heart failure patients. This discrepancy has not been fully resolved, but it may be related to the adiponectin gene (ADIPOQ) which regulates adiponectin production. We aimed to investigate whether the relationship between adiponectin and arterial stiffness is associated with ADIPOQ rs1501299 G/T polymorphism in nondiabetic Korean men.MethodsIn nondiabetic men without disease (n = 301), anthropometric parameters, lipid profiles, IR, circulating adiponectin, and brachial-ankle pulse wave velocity (baPWV) were measured. rs1501299 G/T polymorphism was also analyzed.ResultsCirculating adiponectin levels were negatively correlated with baPWV and homeostatic model assessment-IR in the T allele carriers (n = 167), but this correlation was not observed in the GG subjects (n = 134). However, a positive correlation between baPWV and IR was observed in the GG subjects, but not in the T carriers. These patterns were maintained after the adjustment for confounding factors. A stepwise linear regression analysis revealed that circulating adiponectin and systolic blood pressure (BP) were the main influencing factors on baPWV levels in T carriers, but systolic BP, IR and age were the main contributors to increased baPWV levels in the GG subjects.ConclusionsThis study demonstrates that the relationship between circulating adiponectin and arterial stiffness is different according to ADIPOQ rs1501299 G/T polymorphism, and suggests that T allele is more susceptible to the influence of adiponectin on arterial stiffness than GG homozygotes. This information may prove to be useful for personal-based early prevention and management of atherosclerotic risk.

ADIPOQ rs1501299 G/T Polymorphism is Associated with the Relationship Between Circulating Adiponectin and Arterial Stiffness in Nondiabetic Individuals

ADIPOQ rs1501299 G/T Polymorphism is Associated with the Relationship Between Circulating Adiponectin and Arterial Stiffness in Nondiabetic Individuals

Adiponectin gene polymorphisms and obesity increase the susceptibility to arsenic-related renal cell carcinoma

Our recent study found that high urinary total arsenic levels were associated with renal cell carcinoma (RCC). Recent studies demonstrated that low circulating adiponectin was related to RCC. The aim of the present study was to explore the relationship between adiponectin gene (ADIPOQ) polymorphisms and RCC and investigate whether individuals with an ADIPOQ risk genotype, obesity, and high urinary total arsenic levels have a modified odds ratio (OR) of RCC. A total of 389 RCC patients and 389 age- and sex-matched controls were recruited between November 2006 and December 2012 in Taiwan. Image-guided biopsy or surgical resection of renal tumors was performed to pathologically verify RCC. Genomic DNA was used to examine the genotypes of the ADIPOQ rs182052, ADIPOQ rs2241766, ADIPOQ rs1501299, and ADIPOQ rs1063539 SNPs by PCR-RFLP. HPLC-HG-AAS was used to measure the concentrations of urinary arsenic species. Participants with the ADIPOQ rs182052 G/A+A/A genotype had a significantly higher OR of RCC compared with those with the ADIPOQ rs182052 G/G genotype. The OR (95% confidence interval [CI]) was 1.70 (1.23–2.36). The OR of RCC for the combined effect of high urinary total arsenic levels and obesity, which was dose-dependent, in individuals with the ADIPOQ rs182052 G/A+A/A genotype was 9.33 (3.85–22.62). The present study found significant combined effects of obesity and the ADIPOQ rs182052 G/A+A/A genotype on the arsenic-related risk of RCC in a population with low arsenic exposure. Arsenic exposure, obesity, and the ADIPOQ rs182052 polymorphism could be predictors of a higher OR of RCC.