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Association of obesity with variations at selected gene loci
Author(s) -
McDermott Ann Yelmokas,
Kirkendall Rosanna,
Brousseau Margaret E.,
Parnell Larry,
Polisecki Eliana Y.,
Schaefer Ernst J.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1036-a
Subject(s) - medicine , endocrinology , waist , single nucleotide polymorphism , bioelectrical impedance analysis , obesity , minor allele frequency , body mass index , leptin , biology , genetics , genotype , gene
Obesity involves a complex relationship between energy balance and genetic factors. We hypothesized 15 single nucleotide polymorphisms (SNPs) that affect function/expression of 8 obesity‐related genes, including: Dopamine Receptor ( DRD2: rs6279 ), Ghrelin ( GHRL: L72M, Q90L ), Leptin Receptor ( LPR : Q223R, K109R ), Melanocortin4 Receptor ( MC4R: rs2229616 ), Neuropeptide Y ( NPY: S50S, S68S ), Proprotein convertase subtilisin/kexin type1 ( PCK1: S690S, N550N, Q665E ), Pro‐opiomelanocortin ( POMC: rs1042571 ), or Uncoupling Protein3 ( UCP3: Y210Y, rs2734827, rs1800849 ), would be associated with BMI, central adiposity, lean and fat mass in a cohort of extremely obese adults. Subjects [n= 217; 77% women; mean age 45.4±10.8 y] completed baseline measures including height, weight, waist, bioelectrical impedance and fasting blood. Current BMI (kg/m 2 ) was 42.1 (median, IQR: 35.1–47.7) and highest recorded BMI 48.8 (IQR: 45.6–57.9). Fat mass accounted for 52.9% of women's weight vs. 32.9% of men's. Waist circumference was 128.8±21.8 cm in women and 137.6±21.2 cm in men. In adjusted models (sex, age and BMI), >lean mass was associated with UCP3 rs1800849 minor alleles (TT: coeff. 3.3%, p=0.01, CT: 1.1%, p=0.05). Minor alleles in PCK1 S690S and Q665E (coeff. 1.6% and 1.7%, both p<0.005) and UCP3 Y210Y and rs2734827 (coeff. 5.0% and 4.3%, both p<0.05) predicted more fat. We found UCP3 SNPs associated with lean and fat mass, and PCK1 with fat. Although some approached significance, DRD2, GHRL LPR, MC4R, NPY and POMC were not associated with these outcomes. Funding: NIH F32 DK064512 ‐03