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- Title
Sequence Variants in the Developmental Gene T-box 15 (TBX15) Are Major Modulators of Body Weight and Waist Circumference.
- Authors
Powers, Christine; Gottardo, Lucia; Placha, Grzegorz; Gesta, Stephane; Avogaro, Angelo; Kahn, C. Ronald; Doria, Alessandro
- Abstract
Gene expression profiling of intraabdominal and subcutaneous adipose tissues has revealed depot-specific differences in the expression of 10 genes involved in embryonic development and pattern specification (PNAS 103:3376, 2006). Three of these genes (T-box 15, Glypican 4, Hox A5) also exhibited changes in expression that correlate closely with body weight and waist-hip ratio. In the present study, we investigated whether single nucleotide polymorphisms in these genes or the others that were differentially expressed between fat depots (Hox C8 and C9, Shox 2, Engrailed 1, Sfrp 2, Thrombomodulin, and Nr2f 1) might influence the obesity phenotype. Linkage disequilibrium analysis of these 10 genes and their flanking regions yielded 19 blocks, which could be tagged by 120 SNPs. These markers were typed in a population of healthy, Caucasian, non-diabetic individuals (n=697). Additive, dominant, and recessive models of inheritance were used to test the association between each SNP and % ideal body weight (%IBW) as well as waist circumference. A highly significant association was observed for both traits with TBX15 SNP rs1750330 under a dominant model (p= 5.7x10[sup -5] and 2.0x10[sup -3], respectively). Interestingly, this effect was exclusively observed in women (p=2.0x10[sup -5] and 2.0x10[sup -4] for %IBW and waist, respectively). Indeed, female homozygotes, for the rs1750330 major allele had a three-fold increase (95% CI 1.5-6.0) in the risk of being overweight Or obese as compared to minor allele carriers. Six other SNPs at the TBX15 locus, all in LD with rs1750330, were also significantly associated with %IBW. Of the remaining nine genes, only Hox A5 (HOXA5) and Glypican 4 (GPC4) displayed significant associations with %IBW, although these were not as strong as those observed for TBX15. These findings suggest that genetic variability in TBX15 is a major determinant of body weight and waist circumference, especially in women, supporting a role of this gene as a major regulator of body fat amount and distribution.
- Subjects
NUCLEOTIDE sequence; GENES; BODY weight; BODY size; GENE expression
- Publication
Diabetes, 2007, Vol 56, pA70
- ISSN
0012-1797
- Publication type
Article