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The cell death-inducing DFFA (DNA fragmentation factor-α)-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-α (TNF-α) in fat cells. We hypothesize that CIDEA alleles regulate human obesity through impact on basal metabolic rate and adipocyte TNF-α signaling. Diabetes 54:3032-3034, 2005
The cell death-inducing DFFA (DNA fragmentation factor-α)-like effector A (CIDEA) gene has been implicated as an important regulator of body weight in mice and humans and is therefore a candidate gene for human obesity. Several factors support that CIDEA is involved in the regulation of body weight. CIDEA-null mice are resistant to diet-induced obesity and diabetes and display higher metabolic rate and lipolysis in brown adipose tissue than their wild-type littermates (1). In obese women undergoing weight reduction through low-calorie diet, mRNA for CIDEA is the highest upregulated in subcutaneous adipose tissue among 8,000 investigated genes (2). Furthermore, CIDEA mRNA is downregulated in subcutaneous adipose tissue of obese subjects (3).
Obesity is the strongest risk factor for the development of type 2 diabetes, and there is a marked parallel increase in the prevalence of these two disorders in most countries. Although a genetic impact on common obesity is established, underlying susceptibility genes are largely unknown. The CIDEA gene is encoded on human chromosome 18p11.21. This region is established among Caucasians as a susceptibility locus for type 2 diabetes in connection with obesity (4). In addition, Chagnon et al. (5) has reported linkage and association of polymorphisms in the melanocortin receptor 5 (MC5R) gene on chromosome 18p11.2 with BMI. As far as we know, there is no...