Dataset Information

Common Variations in Perilipin rs1052700 and FTO rs3751812 Gene Variants, and Risk for Obesity and Type-2 Diabetes.

ABSTRACT: BACKGROUND:Perilipins are proteins that coat lipid globules in adipocytes, which are steroid-generating cells that play a central role in lipid storage and breakdown. The FTO gene is associated with type-2 diabetes (T2D) and increased fat mass. In this work the association of perilipin and FTO gene polymorphisms in T2D was investigated. METHODS:One hundred eighty-three Iranian men and women with T2D, and 174 healthy controls with no known metabolic diseases, participated in the study. The subjects were genotyped using tetra-primer amplification refractory mutation system-polymerase chain reaction (Tetra-ARMS-PCR) and their clinical traits were analyzed. RESULTS:A significant association was found between the perilipin rs1052700 polymorphism and T2D, and between the FTO rs3751812 polymorphism and obesity (P = 0.03 and 0.003, respectively); however, no significant relationship was found between rs3751812 and T2D. CONCLUSION:The FTO rs3751812 polymorphism is a major genetic determinant of obesity, but not T2D. The perilipin rs1052700 polymorphism is related to T2D but not obesity.

SUBMITTER: Saravani R

PROVIDER: S-EPMC5643444 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Common Variations in Perilipin rs1052700 and FTO rs3751812 Gene Variants, and Risk for Obesity and Type-2 Diabetes.

Saravani Ramin R Galavi Hamid Reza HR Noorzehi Nafiseh N Ranjbar Nasrin N Mollashahee-Kohkan Fatemeh F

Reports of biochemistry & molecular biology 20171001 1

<h4>Background</h4>Perilipins are proteins that coat lipid globules in adipocytes, which are steroid-generating cells that play a central role in lipid storage and breakdown. The FTO gene is associated with type-2 diabetes (T2D) and increased fat mass. In this work the association of <i>perilipin</i> and FTO gene polymorphisms in T2D was investigated.<h4>Methods</h4>One hundred eighty-three Iranian men and women with T2D, and 174 healthy controls with no known metabolic diseases, participated in ...[more]

PMID: 29090233

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Project description:Aims/hypothesisGenome-wide association (GWA) studies have identified hundreds of common genetic variants associated with obesity and type 2 diabetes. These studies have usually focused on additive association tests. Identifying deviations from additivity may provide new biological insights and explain some of the missing heritability for these diseases.MethodsWe performed a GWA study using a dominance deviation model for BMI, obesity (29,925 cases) and type 2 diabetes (4,040 cases) in 120,286 individuals of British ancestry from the UK Biobank study. We also investigated whether single nucleotide polymorphisms previously shown to be associated with these traits showed any enrichment for departures from additivity.ResultsKnown obesity-associated variants in FTO showed strong evidence of deviation from additivity (p DOMDEV = 3 × 10(-5)) through a recessive effect of the allele associated with higher BMI. The average BMI of individuals carrying zero, one or two BMI-raising alleles was 27.27 (95% CI 27.22, 27.31) kg/m(2), 27.54 (95% CI 27.50, 27.58) kg/m(2) and 28.07 (95% CI 28.00, 28.14) kg/m(2), respectively. A similar effect was observed in 105,643 individuals from the GIANT Consortium (p DOMDEV = 0.003; meta-analysis p DOMDEV = 1 × 10(-7)). For type 2 diabetes, we detected a recessive effect (p DOMDEV = 5 × 10(-4)) at CDKAL1. Relative to homozygous non-risk allele carriers, homozygous risk allele carriers had an OR of 1.48 (95% CI 1.32, 1.65), while the heterozygous group had an OR of 1.06 (95% CI 0.99, 1.14), a result consistent with that of a previous study. We did not identify any novel associations at genome-wide significance.Conclusions/interpretationAlthough we found no evidence of widespread non-additive genetic effects contributing to obesity and type 2 diabetes risk, we did find robust examples of recessive effects at the FTO and CDKAL1 loci.Access to research materialsSummary statistics are available at www.t2diabetesgenes.org and by request (a.r.wood@exeter.ac.uk). All underlying data are available on application from the UK Biobank.

Project description:BackgroundRecent genome-wide association (GWA) studies have identified several unsuspected genes associated with type 2 diabetes (T2D) with previously unknown functions. In this investigation, we have examined the role of 9 most significant SNPs reported in GWA studies: [peroxisome proliferator-activated receptor gamma 2 (PPARG2; rs 1801282); insulin-like growth factor two binding protein 2 (IGF2BP2; rs 4402960); cyclin-dependent kinase 5, a regulatory subunit-associated protein1-like 1 (CDK5; rs7754840); a zinc transporter and member of solute carrier family 30 (SLC30A8; rs13266634); a variant found near cyclin-dependent kinase inhibitor 2A (CDKN2A; rs10811661); hematopoietically expressed homeobox (HHEX; rs 1111875); transcription factor-7-like 2 (TCF7L2; rs 10885409); potassium inwardly rectifying channel subfamily J member 11(KCNJ11; rs 5219); and fat mass obesity-associated gene (FTO; rs 9939609)].MethodsWe genotyped these SNPs in a case-control sample of 918 individuals consisting of 532 T2D cases and 386 normal glucose tolerant (NGT) subjects of an Asian Sikh community from North India. We tested the association between T2D and each SNP using unconditional logistic regression before and after adjusting for age, gender, and other covariates. We also examined the impact of these variants on body mass index (BMI), waist to hip ratio (WHR), fasting insulin, and glucose and lipid levels using multiple linear regression analysis.ResultsFour of the nine SNPs revealed a significant association with T2D; PPARG2 (Pro12Ala) [odds ratio (OR) 0.12; 95% confidence interval (CI) (0.03-0.52); p = 0.005], IGF2BP2 [OR 1.37; 95% CI (1.04-1.82); p = 0.027], TCF7L2 [OR 1.64; 95% CI (1.20-2.24); p = 0.001] and FTO [OR 1.46; 95% CI (1.11-1.93); p = 0.007] after adjusting for age, sex and BMI. Multiple linear regression analysis revealed significant association of two of nine investigated loci with diabetes-related quantitative traits. The 'C' (risk) allele of CDK5 (rs 7754840) was significantly associated with decreased HDL-cholesterol levels in both NGT (p = 0.005) and combined (NGT and T2D) (0.005) groups. The less common 'C' (risk) allele of TCF7L2 (rs 10885409) was associated with increased LDL-cholesterol (p = 0.010) in NGT and total and LDL-cholesterol levels (p = 0.008; p = 0.003, respectively) in combined cohort.ConclusionTo our knowledge, this is first study reporting the role of some recently emerged loci with T2D in a high risk population of Asian Indian origin. Further investigations are warranted to understand the pathway-based functional implications of these important loci in T2D pathophysiology in different ethnicities.

Dataset Information

Common Variations in Perilipin rs1052700 and FTO rs3751812 Gene Variants, and Risk for Obesity and Type-2 Diabetes.

Publications

Common Variations in Perilipin rs1052700 and FTO rs3751812 Gene Variants, and Risk for Obesity and Type-2 Diabetes.

Similar Datasets

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