title: The CIDEA gene V115F polymorphism is associated with obesity in Swedish subjects.
abstract: The cell death-inducing DFFA (DNA fragmentation factor-alpha)-like effector A (CIDEA) gene is implicated as an important regulator of body weight in mice and humans and is therefore a candidate gene for human obesity. Here, we characterize common CIDEA gene polymorphisms and investigate them for association with obesity in two independent Swedish samples; the first comprised 981 women and the second 582 men. Both samples display a large variation in BMI. The only detected coding polymorphism encodes an exon 4 V115F amino acid substitution, which is associated with BMI in both sexes (P = 0.021 for women, P = 0.023 for men, and P = 0.0015 for joint analysis). These results support a role for CIDEA alleles in human obesity. CIDEA-deficient mice display higher metabolic rate, and the gene cross-talks with tumor necrosis factor-alpha (TNF-alpha) in fat cells. We hypothesize that CIDEA alleles regulate human obesity through impact on basal metabolic rate and adipocyte TNF-alpha signaling.
authors.affiliation: Department of Medicine, Huddinge, Karolinska Institute, Stockholm, Sweden.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Dahlman
authors.forename: Maria
authors.initials: M
authors.lastname: Kaaman
authors.forename: Hong
authors.initials: H
authors.lastname: Jiao
authors.forename: Juha
authors.initials: J
authors.lastname: Kere
authors.forename: Markku
authors.initials: M
authors.lastname: Laakso
authors.forename: Peter
authors.initials: P
authors.lastname: Arner
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000502:physiology; D001481:Basal Metabolism / Q000235:genetics; D015992:Body Mass Index; D005091:Exons; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011506:Proteins / Q000737:chemistry / Q000235:genetics*; D017385:Sequence Homology; D013548:Sweden; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D051017:Apoptosis Regulatory Proteins; C502539:CIDEA protein, human; C112510:Cidea protein, mouse; D011506:Proteins; D014409:Tumor Necrosis Factor-alpha