title: The SH2B gene is associated with serum leptin and body fat in normal female twins.
abstract: Src-homology-2 (SH2)-B, a Janus tyrosine kinase 2-interacting protein, has been identified recently as a key regulator of leptin and insulin sensitivity, glucose homeostasis, and body weight in mice. The aim of this study was to determine whether single-nucleotide polymorphisms (SNPs) in the human SH2B gene are associated with these variables. A tagging SNP (tSNP), Ala484Thr (rs7498665), was selected to represent five common SNPs (minor allele frequency > 0.05) in perfect linkage disequilibrium in a 16-kb region encompassing the SH2B gene. The tSNP was genotyped in 2455 white female twins (mean age, 47.4 +/- 12.6 years) from the St. Thomas' United Kingdom Adult Twin Registry (Twins United Kingdom). Ala484Thr (minor allele frequency, 0.38) was associated with serum leptin, total fat, waist circumference, and body weight (P = 0.02 to 0.04). The coding SNP has no predicted effect on protein structure or function and is likely to be in linkage disequilibrium with an as-yet unidentified functional variant in the SH2B gene. Our results support a role for SH2-B in modulating the regulation of body weight and fat by leptin in this female population. If SH2-B signaling is attenuated in diet-induced obesity, it could become a target for drug-induced leptin sensitization.
authors.affiliation: Nutrition Food and Health Research Centre, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London SE1 9NH, UK.
authors.forename: Yalda
authors.initials: Y
authors.lastname: Jamshidi
authors.forename: Harold
authors.initials: H
authors.lastname: Snieder
authors.forename: Dongliang
authors.initials: D
authors.lastname: Ge
authors.forename: Tim D
authors.initials: TD
authors.lastname: Spector
authors.forename: Sandra D
authors.initials: SD
authors.lastname: O'Dell
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000273:Adipose Tissue / Q000378:metabolism*; D001823:Body Composition / Q000235:genetics* / Q000502:physiology; D015992:Body Mass Index; D002352:Carrier Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D020738:Leptin / Q000097:blood*; D015810:Linkage Disequilibrium; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D020738:Leptin; C518910:SH2B1 protein, human