Effect of <i>RBP4</i> gene variants on circulating RBP4 concentration and Type 2 diabetes in a Chinese population

Hu, Cheng; Wang, Jia; Zhang, R.; Wang, C.; Lu, Jieli; Wu, Hongmei; Fang, Qichen; Ma, Xiaojing; Xiang, Kun–san

doi:10.1111/j.1464-5491.2007.02314.x

Cited by 31 publications

(23 citation statements)

References 37 publications

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“…This may be due to the lower minor allele frequency of rs3758538 and comparably similar frequencies in cases and controls. Other genetic studies with SNPs in RBP4 have reported association with serum lipid parameters but in our study we failed to observe any significant association of the promoter polymorphisms with serum lipid levels or with other diabetes related parameters [13], [14]. RBP4 has also been implicated in diabetic retinopathy with enhanced expression in cases with proliferative diabetic retinopathy when compared to non–proliferative diabetic retinopathy or no retinopathy [30].…”

Section: Discussioncontrasting

confidence: 86%

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Case-Control Analysis of SNPs in GLUT4, RBP4 and STRA6: Association of SNPs in STRA6 with Type 2 Diabetes in a South Indian Population

et al. 2010

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BackgroundThe inverse relationship between GLUT4 and RBP4 expression is known to play a role in the pathogenesis of type 2 diabetes. Elevated levels of RBP4 were shown to cause insulin resistance in muscles and liver. Identification of STRA6 as a cell surface receptor for RBP4 provides further link in this axis and hence we analyzed SNPs in these three genes for association with type 2 diabetes in a South Indian population.Methodology/Principal FindingsSelected SNPs in the three genes were analyzed in a total of 2002 individuals belonging to Dravidian ethnicity, South India, by Tetra Primer ARMS PCR or RFLP PCR. Allele frequencies and genotype distribution were calculated in cases and controls and were analyzed for association by Chi-squared test and Logistic regression. Haplotype analysis was carried out for each gene by including all the markers in a single block. We observed a significant association of three SNPs, rs974456, rs736118, and rs4886578 in STRA6 with type 2 diabetes (P = 0.001, OR 0.79[0.69–0.91], P = 0.003, OR 0.81[0.71–0.93], and P = 0.001, OR 0.74[0.62–0.89] respectively). None of the SNPs in RBP4 and GLUT4 showed any association with type 2 diabetes. Haplotype analysis revealed that two common haplotypes H1 (111, P = 0.001, OR 1.23[1.08–1.40]) and H2 (222, P = 0.002 OR 0.73[0.59–0.89]) in STRA6, H6 (2121, P = 0.006, OR 1.69[1.51–2.48]) in RBP4 and H4 (2121, P = 0.01 OR 1.41[1.07–1.85]) in GLUT4 were associated with type 2 diabetes.ConclusionSNPs in STRA6, gene coding the cell surface receptor for RBP4, were significantly associated with type 2 diabetes and further genetic and functional studies are required to understand and ascertain its role in the manifestation of type 2 diabetes.

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Section: Discussioncontrasting

confidence: 86%

“…None of these studies focused on SNPs present in the promoter and coding region of GLUT4. Recent studies in other populations have identified common variants and haplotypes in RBP4 to be associated with type 2 diabetes [11], [13]. Other studies have also identified SNPs in RBP4 to be associated with altered serum lipid levels (12,14).…”

Section: Introductionmentioning

confidence: 99%

Case-Control Analysis of SNPs in GLUT4, RBP4 and STRA6: Association of SNPs in STRA6 with Type 2 Diabetes in a South Indian Population

et al. 2010

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“…All the controls were over 40 years old and had no family history of diabetes according to self-report questionnaire data. The clinical characteristics of the study groups are shown in Electronic supplementary material (ESM) Clinical studies All participants underwent a detailed clinical investigation as described previously [7,9]. Briefly, anthropometric variables such as height, weight, waist and hip circumference and blood pressure were measured.…”

Section: Methodsmentioning

confidence: 99%

A genetic variant of G6PC2 is associated with type 2 diabetes and fasting plasma glucose level in the Chinese population

Zhang

Wang

et al. 2008

Diabetologia

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Aims/hypothesis Single nucleotide polymorphisms (SNPs) in G6PC2 have been reported to be associated with fasting plasma glucose level in several populations of European descent. However, whether G6PC2 variants have a similar effect in other ethnic groups is unknown. The aim of this study was to investigate the effect of common variants of G6PC2 on type 2 diabetes and related clinical features in a Chinese population. Methods We selected four SNPs, rs13387347, rs2232316, rs492594 and rs16856187, tagging all the common variants spanning the G6PC2 gene (r 2 ≥0.8) based on HapMap Chinese data, and genotyped them in a group of 3,676 Shanghai Chinese individuals, comprising 1,876 cases and 1,800 controls. Results Three SNPs were nominally associated with type 2 diabetes, with rs16856187 showing the strongest evidence for association (p=0.0009, empirical p=0.0047). Further conditional analysis revealed that the association signal arose from an individual SNP, rs16856187. This SNP was also associated with fasting plasma glucose level in participants with normal glucose regulation (p=0.0002), with the fasting plasma glucose level observed to increase by 0.067 mmol/l with each copy of the rare C allele. Conclusions/interpretation In this study we identified a novel risk-conferring G6PC2 SNP for type 2 diabetes in a Chinese population and confirmed the previous finding that G6PC2 variants are associated with fasting plasma glucose concentration.

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“…In addition, genes could play a role in determination of plasma RBP4, since certain single nucleotide polymorphisms in the RBP4 gene promoter have been shown to be associated with elevated plasma RBP4 (10). Nevertheless, little is known about the relative importance of genes versus environmental factors in determination of plasma RBP4.…”

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confidence: 99%

Retinol-Binding Protein 4 in Twins

et al. 2009

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OBJECTIVE-Retinol-binding protein (RBP) 4 is an adipokine of which plasma levels are elevated in obesity and type 2 diabetes. The aims of the study were to identify determinants of plasma RBP4 and RBP4 mRNA expression in subcutaneous adipose tissue (SAT) and skeletal muscle and to investigate the association between RBP4 and in vivo measures of glucose metabolism. RESEARCH DESIGN AND METHODS-The study population included 298 elderly twins (aged 62-83 years), with glucose tolerance ranging from normal to overt type 2 diabetes, and 178 young (aged 25-32 years) and elderly (aged 58 -66 years) nondiabetic twins. Peripheral and hepatic insulin sensitivity was assessed by a euglycemic-hyperinsulinemic clamp, and ␤-cell function was estimated from an intravenous glucose tolerance test.RESULTS-The influence of environmental versus genetic factors in the regulation of plasma RBP4 increased with age. Plasma RBP4 was elevated in type 2 diabetes and increased with duration of disease. Plasma RBP4 correlated inversely with peripheral, but not hepatic, insulin sensitivity. However, the association disappeared after correction for covariates, including plasma adiponectin. Plasma retinol, and not RBP4, was inversely associated with insulin secretion. SAT RBP4 expression correlated positively with GLUT4 expression and inversely with glucose tolerance. Skeletal muscle RBP4 expression reflected intramuscular fat, and although it was suppressed by insulin, no association with insulin sensitivity was evident. RBP4 expression was not associated with circulatory RBP4.CONCLUSIONS-In conclusion, our data indicate that RBP4 levels in plasma, skeletal muscle, and fat may be linked to insulin resistance and type 2 diabetes in a secondary and noncausal manner. Diabetes 58:54-60, 2009

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Effect of RBP4 gene variants on circulating RBP4 concentration and Type 2 diabetes in a Chinese population

Abstract: Our findings suggest that genetic variants in the RBP4 gene may be associated with circulating RBP4 concentration and phenotypes related to glucose metabolism.

Cited by 31 publications

References 37 publications

Case-Control Analysis of SNPs in GLUT4, RBP4 and STRA6: Association of SNPs in STRA6 with Type 2 Diabetes in a South Indian Population

Case-Control Analysis of SNPs in GLUT4, RBP4 and STRA6: Association of SNPs in STRA6 with Type 2 Diabetes in a South Indian Population

A genetic variant of G6PC2 is associated with type 2 diabetes and fasting plasma glucose level in the Chinese population

Retinol-Binding Protein 4 in Twins

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