Dataset Information

Common variations in perilipin gene, central obesity, and risk of type 2 diabetes in US women.

ABSTRACT: The variations in perilipin gene (PLIN) were previously associated with obesity and insulin sensitivity. We examined whether PLIN variability was associated with diabetes risk and obesity status modified such associations.We conducted a nested case-control study of 431 incident cases of type 2 diabetes and 791 healthy control women from the Nurses' Health Study. Obesity was defined by BMI or waist circumference (central obesity).In the sample of all participants, PLIN variations were not significantly associated with the incidence of diabetes. The central obesity status (by National Cholesterol Education Program Adult Treatment Panel III definition of waist circumference>35 inches) significantly interacted with PLIN polymorphisms in relation to diabetes risk (P for interaction=0.027, 0.009, and 0.02 for rs2289487, rs8179043, and rs894160, respectively). In nonobese (central) women, carriers of rs2289487, rs8179043, and rs894160 had significantly greater risk of type 2 diabetes, adjusting for diabetes risk factors (odds ratio (OR)=1.52, 1.03-2.25; 1.54, 1.07-2.23; and 1.57, 1.09-2.27, respectively). Haplotypes possessing the three polymorphisms were also significantly associated with diabetes risk (global test, P=0.01). As compared with the most common haplotype 111, haplotype 222 and 211 (1 codes the common and 2 codes the minor alleles) were associated with 44% (OR=1.44, 95% confidence interval (CI) 1.09-1.91; P=0.01) and 70% (OR=1.70, 95% CI 1.04-2.77; P=0.03) greater risk, respectively. The PLIN variations were not significantly associated with the disease risk among women with central obesity.Our data indicate that central obesity may modify the associations between PLIN variations and diabetes risk in women.

SUBMITTER: Qi L

PROVIDER: S-EPMC3925667 | biostudies-literature | 2008 May

REPOSITORIES: biostudies-literature

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Common variations in perilipin gene, central obesity, and risk of type 2 diabetes in US women.

Qi Lu L Zhang Cuilin C Greenberg Andrew A Hu Frank B FB

Obesity (Silver Spring, Md.) 20080306 5

<h4>Objective</h4>The variations in perilipin gene (PLIN) were previously associated with obesity and insulin sensitivity. We examined whether PLIN variability was associated with diabetes risk and obesity status modified such associations.<h4>Methods and procedures</h4>We conducted a nested case-control study of 431 incident cases of type 2 diabetes and 791 healthy control women from the Nurses' Health Study. Obesity was defined by BMI or waist circumference (central obesity).<h4>Results</h4>In ...[more]

PMID: 18356850

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Project description:OBJECTIVES:Despite recommendations that central obesity assessment should be employed as a marker of cardiometabolic health, no consensus exists regarding measurement protocol. This study examined a range of anthropometric variables and their relationships with cardiometabolic features and type 2 diabetes in order to ascertain whether measurement site influences discriminatory accuracy. In particular, we compared waist circumference (WC) measured at two sites: (1) immediately below the lowest rib (WC rib) and (2) between the lowest rib and iliac crest (WC midway), which has been recommended by the World Health Organisation and International Diabetes Federation. MATERIALS AND METHODS:This was a cross-sectional study involving a random sample of 2,002 men and women aged 46-73 years. Metabolic profiles and WC, hip circumference, pelvic width and body mass index (BMI) were determined. Correlation, logistic regression and area under the receiver operating characteristic curve analyses were used to evaluate obesity measurement relationships with metabolic risk phenotypes and type 2 diabetes. RESULTS:WC rib measures displayed the strongest associations with non-optimal lipid and lipoprotein levels, high blood pressure, insulin resistance, impaired fasting glucose, a clustering of metabolic risk features and type 2 diabetes, in both genders. Rib-derived indices improved discrimination of type 2 diabetes by 3-7% compared to BMI and 2-6% compared to WC midway (in men) and 5-7% compared to BMI and 4-6% compared to WC midway (in women). A prediction model including BMI and central obesity displayed a significantly higher area under the curve for WC rib (0.78, P=0.003), Rib/height ratio (0.80, P<0.001), Rib/pelvis ratio (0.79, P<0.001), but not for WC midway (0.75, P=0.127), when compared to one with BMI alone (0.74). CONCLUSIONS:WC rib is easier to assess and our data suggest that it is a better method for determining obesity-related cardiometabolic risk than WC midway. The clinical utility of rib-derived indices, or alternative WC measurements, deserves further investigation.

Project description:The protein tyrosine phosphatase-1B, a negative regulator for insulin and leptin signalling, potentially modulates glucose and energy homeostasis. PTP1B is encoded by the PTPN1 gene located on chromosome 20q13 showing linkage with type 2 diabetes (T2D) in several populations. PTPN1 gene variants have been inconsistently associated with T2D, and the aim of our study was to investigate the effect of PTPN1 genetic variations on the risk of T2D, obesity and on the variability of metabolic phenotypes in the French population.Fourteen single nucleotide polymorphisms (SNPs) spanning the PTPN1 locus were selected from previous association reports and from HapMap linkage disequilibrium data. SNPs were evaluated for association with T2D in two case-control groups with 1227 cases and 1047 controls. Association with moderate and severe obesity was also tested in a case-control study design. Association with metabolic traits was evaluated in 736 normoglycaemic, non-obese subjects from a general population. Five SNPs showing a trend towards association with T2D, obesity or metabolic parameters were investigated for familial association.From 14 SNPs investigated, only SNP rs914458, located 10 kb downstream of the PTPN1 gene significantly associated with T2D (p = 0.02 under a dominant model; OR = 1.43 [1.06-1.94]) in the combined sample set. SNP rs914458 also showed association with moderate obesity (allelic p = 0.04; OR = 1.2 [1.01-1.43]). When testing for association with metabolic traits, two strongly correlated SNPs, rs941798 and rs2426159, present multiple consistent associations. SNP rs2426159 exhibited evidence of association under a dominant model with glucose homeostasis related traits (p = 0.04 for fasting insulin and HOMA-B) and with lipid markers (0.02 = p = 0.04). Moreover, risk allele homozygotes for this SNP had an increased systolic blood pressure (p = 0.03). No preferential transmission of alleles was observed for the SNPs tested in the family sample.In our study, PTPN1 variants showed moderate association with T2D and obesity. However, consistent associations with metabolic variables reflecting insulin resistance and dyslipidemia are found for two intronic SNPs as previously reported. Thus, our data indicate that PTPN1 variants may modulate the lipid profile, thereby influencing susceptibility to metabolic disease.

Dataset Information

Common variations in perilipin gene, central obesity, and risk of type 2 diabetes in US women.

Publications

Common variations in perilipin gene, central obesity, and risk of type 2 diabetes in US women.

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