title: Effect of six type II diabetes susceptibility loci and an FTO variant on obesity in Pakistani subjects.
abstract: The aim of the current study was to analyze the effect of six type II diabetes GWAS loci rs3923113 (GRB14), rs16861329 (ST6GAL1), rs1802295 (VPS26A), rs7178572 (HMG20A), rs2028299 (AP3S2) and rs4812829 (HNF4A), and an FTO polymorphism (rs9939609) on obesity. The probable mechanism of action of these SNPs was analyzed by studying their association with various biochemical and anthropometric parameters. A total of 475 subjects (obese=250, controls=225) were genotyped by TaqMan assay and their lipid profile was determined. Allele/genotype frequencies and an unweighted/weighted gene score were calculated. The effect of the gene score on anthropometric and biochemical parameters was analyzed. The minor allele frequencies of all variants were comparable to that reported in the original studies and were associated with obesity in these Pakistani subjects. Subjects with 9 risk alleles differ from those with <3 and overall there is no significant effect (P-value for trend 0.26). None of the SNPs were associated with any of the serum lipid traits. We are the first to report the association of these T2D SNPs with obesity. In the Pakistani population the reported effect of six SNPs for obesity is similar to that reported for T2D and having a combination of risk alleles on obesity can be considerable. The mechanism of this effect is unclear, but appears not to be mediated by changing serum lipid chemistry.
authors.affiliation: Department of Microbiology and Molecular Genetics, University of the Punjab, Lahore, Pakistan.
authors.lastname: Shabana
authors.affiliation: Department of Microbiology and Molecular Genetics, University of the Punjab, Lahore, Pakistan.
authors.forename: Saleem
authors.initials: S
authors.lastname: Ullah Shahid
authors.affiliation: Centre for Cardiovascular Genetics, British Heart Foundation Laboratories, The Rayne Building, Institute of Cardiovascular Sciences, University College London, London, UK.
authors.forename: Ka
authors.initials: K
authors.lastname: Wah Li
authors.affiliation: Centre for Cardiovascular Genetics, British Heart Foundation Laboratories, The Rayne Building, Institute of Cardiovascular Sciences, University College London, London, UK.
authors.forename: Jayshree
authors.initials: J
authors.lastname: Acharya
authors.affiliation: Centre for Cardiovascular Genetics, British Heart Foundation Laboratories, The Rayne Building, Institute of Cardiovascular Sciences, University College London, London, UK.
authors.forename: Jackie A
authors.initials: JA
authors.lastname: Cooper
authors.affiliation: Department of Microbiology and Molecular Genetics, University of the Punjab, Lahore, Pakistan.|The Women University, Multan, Pakistan.
authors.forename: Shahida
authors.initials: S
authors.lastname: Hasnain
authors.affiliation: Centre for Cardiovascular Genetics, British Heart Foundation Laboratories, The Rayne Building, Institute of Cardiovascular Sciences, University College London, London, UK.
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Humphries
mesh_terms: D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D009765:Obesity / Q000235:genetics*; D010154:Pakistan; D020641:Polymorphism, Single Nucleotide
chemical_list: D008055:Lipids; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human