Adiponectin Receptor 1 Gene (<i>ADIPOR1</i>) as a Candidate for Type 2 Diabetes and Insulin Resistance

Wang, Hua; Zhang, Hailing; Jia, Yiwen; Zhang, Zhengxian; Craig, Rebekah L.; Wang, Xiaoqin; Elbein, Steven C.

doi:10.2337/diabetes.53.8.2132

Cited by 95 publications

(64 citation statements)

References 24 publications

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“…However, it cannot be excluded that SNPs in ADIPOR1 and/or ADIPOR2 had a minor effect on susceptibility to type 2 diabetes. Consistent with our results for ADPOR1, an American study recently reported that SNPs in ADIPOR1 were not associated with type 2 diabetes in Caucasians or African Americans [20]. However, they reported that the level of expression of ADIPOR1 in lymphocytes from type 2 diabetic subjects was reduced compared with that in lymphocytes from non-diabetic subjects, implicating ADIPOR1 in the pathogenesis of type 2 diabetes.…”

Section: Discussionsupporting

confidence: 91%

Absence of an association between the polymorphisms in the genes encoding adiponectin receptors and type 2 diabetes

et al. 2005

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Aims/hypothesis: Secreted by adipocytes, adiponectin is a hormone that acts as an antidiabetic and anti-atherogenic adipokine. We recently cloned the genes encoding two adiponectin receptors (ADIPOR1 and ADIPOR2). The aim of this study was to examine whether ADIPOR1 and/or ADIPOR2 play a major role in genetic susceptibility to insulin resistance or type 2 diabetes in the Japanese population. Methods: By direct sequencing and a search of public databases, we identified single nucleotide polymorphisms (SNPs) in ADIPOR1 and ADIPOR2, and investigated whether these SNPs are associated with insulin resistance and type 2 diabetes in the Japanese population. Results: The linkage disequilibrium (LD) in the chromosomal region of ADIPOR1 was almost completely preserved, whereas the LD in ADIPOR2 was less well preserved. None of the SNPs in ADIPOR1 or ADIPOR2 were significantly associated with insulin resistance or type 2 diabetes. No differences in ADIPOR1 or ADIPOR2 haplotype frequencies were observed between type 2 diabetic and non-diabetic subjects. Conclusions/interpretation: Genetic variations in ADIPOR1 or ADIPOR2 are unlikely to lead to a common genetic predisposition to insulin resistance or type 2 diabetes in the Japanese population.

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Section: Discussionsupporting

confidence: 91%

Absence of an association between the polymorphisms in the genes encoding adiponectin receptors and type 2 diabetes

et al. 2005

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“…Our findings that haplotypes possessing the tagging SNPs of the ADIPOR1 gene were associated with diabetes risk lend further credibility for the potential roles of the variability of the ADIPOR1 gene in the etiology of the disease. Earlier evidence indicates that the 3Ј UTR polymorphism rs1139646 may affect the expression of the ADIPOR1 gene (15). Although rs1139646 showed the strongest and nominally significantly association with diabetes risk in the present study, it is less likely to be a polymorphic changes (in the order of rs2232853, rs10494839, rs12733285, rs1342387, rs1139646, and rs10920531) separating one haplotype from the other.…”

Section: Discussioncontrasting

confidence: 68%

“…We did not find significant associations between the variations in this gene, individually or in haplotypes, with diabetes risk in U.S. women. We have genotyped several previously reported polymorphisms including rs11061971, rs1044471, rs1342387 (14), and rs1139646 (15). Some other reported polymorphisms, rs767870, rs2286380 (tagged by rs7316374) (17), rs12342 (tagged by rs11061937), and rs2275737 (tagged by rs1342387) (14), could be well captured by the tagging SNPs used in our study (with r 2 Ͼ 0.8).…”

Section: Discussionmentioning

confidence: 54%

Variations in Adiponectin Receptor Genes and Susceptibility to Type 2 Diabetes in Women

Doria²,

Giorgi³

et al. 2007

Diabetes

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Adiponectin has been associated with low diabetes risk. The metabolic effects of adiponectin are mediated by adiponectin receptors 1 (ADIPOR1) and 2 (ADIPOR2). We conducted a prospective, nested case-control study of 714 cases of type 2 diabetes and 1,120 control subjects. Six polymorphisms in ADIPOR1 and 16 polymorphisms in ADI-POR2 were determined. Haplotypes inferred from ADI-POR1 polymorphisms were significantly associated with diabetes risk (overall test, ؊2log-likelihood ‫؍‬ 15.1 on 5 df; P ‫؍‬ 0.0098). A single copy of haplotype 001100 (0, common allele; and 1, minor allele) was associated with 24% M any studies have documented that adiponectin, which is a hormonal cytokine secreted exclusively by adipose tissue, has strong insulin-sensitizing, anti-inflammatory, and antidiabetes effects (1,2). Adiponectin improves insulin sensitivity by affecting the metabolism of glucose and lipids in skeletal muscle and liver (3). In earlier analyses, we have found that blood adiponectin levels and variations in the adiponectin gene (ADIPOQ, also known as APM1) were associated with type 2 diabetes and cardiovascular risk (4 -6).Recent evidence indicates that the metabolic regulation of adiponectin is mainly mediated by two types of receptors, adiponectin receptors 1 (ADIPOR1) and 2 (ADI-POR2) (7,8). Downregulation of ADIPORs may blunt adiponectin-induced signaling (7). The expression of adiponectin receptor has been related to in vivo parameters of glucose and lipid metabolism (9) and was found to be lower in diabetic patients (10). The polymorphisms in the ADIPOR1 gene were recently associated with adiposity, insulin resistance, and high liver fat (11-13). A few studies have investigated the associations between the variations in ADIPOR1 and ADIPOR2 genes and the risk of type 2 diabetes but generated mixed results (14 -17). These studies, however, were largely limited by small sample size or a cross-sectional nature in design. The relation between ADIPOR genetic variability and diabetes risk has yet to be evaluated in prospective settings.In this study, we comprehensively examined the variations in ADIPOR1 and ADIPOR2 genes and the risk of type 2 diabetes in a nested, case-control study from the Nurses' Health Study cohort. We selected linkage disequilibrium (LD) tagging single nucleotide polymorphisms (SNPs) that capture the maximum variance in both genes and also included polymorphisms that were previously associated with diabetes risk. RESEARCH DESIGN AND METHODSThe Nurses' Health Study was established in 1976 when 121,700 female registered nurses aged 30 -55 years and residing in 11 large U.S. states completed a mailed questionnaire on medical history and lifestyle (18). The lifestyle factors, including smoking, menopausal status and postmenopausal hormone therapy, and body weight, have been updated by validated questionnaires every 2 years. Samples for the present case-control study were selected from a subcohort of 32,826 women who provided a blood sample between 1989 and 1990 and were free from diabetes, cardio...

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“…1a). Among them, three SNPs were already reported in the dbSNP database (http://ncbi.nlm.nih.gov/projects/SNP, last accessed in August 2005) and one SNP (9512 G/A) was recently found by Wang and colleagues [24] (Table 1). Pairwise linkage disequilibrium for the SNPs is shown in Table 2.…”

Section: Screening For Polymorphisms and Genotyping Resultsmentioning

confidence: 99%

“…Most recently, the group of Elbein found that SNPs in ADIPOR1 were not associated with type 2 diabetes [24]. Nevertheless, two alleles in the 3′ untranslated region were expressed unequally and mRNA of ADIPOR1 were lower among transformed lymphocytes from diabetic AfricanAmerican individuals compared with healthy controls.…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms in the gene encoding adiponectin receptor 1 are associated with insulin resistance and high liver fat

et al. 2005

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Aims/hypothesis: The adipokine adiponectin has insulin-sensitising, anti-atherogenic and anti-inflammatory properties. Recently, the genes for mouse and human adiponectin receptor-1 (ADIPOR1) and -2 (ADIPOR2) have been cloned. The aim of this study was to investigate whether genetic variants of the genes encoding ADIPOR1 and ADIPOR2 play a role in human metabolism. Materials and methods: We screened ADIPOR1 and ADIPOR2 for polymorphisms and determined their association with glucose metabolism, lipid metabolism, an atherogenic lipid profile and inflammatory markers in 502 non-diabetic subjects. A subgroup participated in a longitudinal study; these subjects received diet counselling and increased their physical activity. Results: We identified six variants of ADIPOR1 and seven variants of ADIPOR2. A single-nucleotide polymorphism (SNP) in the putative promoter region 8503 bp upstream of the translational start codon (−8503 G/A) of ADIPOR1 (frequency of allele A=0.31) was in almost complete linkage disequilibrium with another SNP (−1927 T/C) in intron 1. Subjects carrying the −8503 A and −1927 C alleles had lower insulin sensitivity, as estimated from a 75 g OGTT (p=0.04) and determined during a euglycaemic clamp (n=295, p=0.04); they also had higher HbA 1 c levels (p=0.02) and, although the difference was not statistically significant, higher liver fat (n=85, determined by proton magnetic resonance spectroscopy, p=0.056) (all p values are adjusted for age, sex and percentage of body fat). In the longitudinal study (n=45), the −8503 A and −1927 C alleles were associated with lower insulin sensitivity (p=0.03) and higher liver fat (p=0.02) at follow-up compared with the −8503 G and −1927 T alleles, independently of basal measurements, sex and baseline and follow-up percentage of body fat. Conclusions/interpretation: The present findings suggest that the −8503 G/A SNP in the promoter or the −1927 T/C SNP in intron 1 of ADIPOR1 may affect insulin sensitivity and liver fat in humans.

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Adiponectin Receptor 1 Gene (ADIPOR1) as a Candidate for Type 2 Diabetes and Insulin Resistance

Cited by 95 publications

References 24 publications

Absence of an association between the polymorphisms in the genes encoding adiponectin receptors and type 2 diabetes

Absence of an association between the polymorphisms in the genes encoding adiponectin receptors and type 2 diabetes

Variations in Adiponectin Receptor Genes and Susceptibility to Type 2 Diabetes in Women

Polymorphisms in the gene encoding adiponectin receptor 1 are associated with insulin resistance and high liver fat

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