Background: Type 2 diabetes (T2D) is a metabolic disorder characterized by disturbances of carbohydrate, fat and protein metabolism and insulin resistance. The majority of T2D patients are obese and obesity by itself may be a cause of insulin resistance. Our aim was to evaluate whether the recently identified T2D risk alleles are associated with human measures of fatness as characterized with Dual Energy X-ray Absorptiometry (DEXA). Methodology/Principal Findings: Genotypes and phenotypes of approximately 3,000 participants from cross-sectional ERF study were analyzed. Nine single nucleotide polymorphisms (SNPs) in CDKN2AB, CDKAL1, FTO, HHEX, IGF2BP2, KCNJ11, PPARG, SLC30A8 and TCF7L2 were genotyped. We used linear regression to study association between individual SNPs and the combined allelic risk score with body mass index (BMI), fat mass index (FMI), fat percentage (FAT), waist circumference (WC) and waist to hip ratio (WHR). Significant association was observed between rs8050136 (FTO) and BMI (p = 0.003), FMI (p = 0.007) and WC (p = 0.03); fat percentage was borderline significant (p = 0.053). No other SNPs alone or combined in a risk score demonstrated significant association to the measures of fatness. Conclusions/Significance: From the recently identified T2D risk variants only the risk variant of the FTO gene (rs8050136) showed statistically significant association with BMI, FMI, and WC.

CDKAL1 gene, FTO gene, HHEX gene, IGF2BP2 gene, SLC30A8 gene, adult, aged, allele, article, body fat, body mass, clinical evaluation, cross-sectional study, cyclin dependent kinase inhibitor 2B, dual energy X ray absorptiometry, female, gene, gene identification, gene locus, genetic association, genetic risk, genetic variability, genotype, human, inwardly rectifying potassium channel subunit Kir6.2, major clinical study, male, non insulin dependent diabetes mellitus, peroxisome proliferator activated receptor gamma, phenotype, scoring system, single nucleotide polymorphism, waist circumference, waist hip ratio,
Erasmus MC: University Medical Center Rotterdam

Pecioska, S, Zillikens, M.C, Henneman, P, Snijders, P.J, Oostra, B.A, van Duijn, C.M, & Aulchenko, Y.S. (2010). Association between type 2 diabetes loci and measures of fatness. PLoS ONE, 5(1). doi:10.1371/journal.pone.0008541