A UCP1-412A>C polymorphism is associated with abdominal fat area in Korean women.

We used genomic sequencing of Korean subjects to identify the uncoupling protein-1 (UCP1) polymorphism -412A>C (rs3811787 in the dbSNP database). This study is the first to associate this polymorphism with a human phenotype. The frequency of the major A allele was 0.53 and that of the minor C allele was 0.47. The -412A>C polymorphism was not linked to the well-known -3826A>G (rs1800592; mid R:D'mid R:=0.60 and r(2)=0.33), yielding four predicted haplotypes from these two polymorphisms. We associated -412A>C, -3826A>G and their haplotypes with computed tomography-measured body fat areas from 367 Korean female subjects. The G allele of -3826A>G and the C allele of -412A>C were significantly associated with larger areas of abdominal subcutaneous fat in a dominant model (p=0.001 and p=0.0004, respectively); combining them together (ht2[GC]) enhanced this significance (p=0.00005). In contrast, presence of the A allele in both polymorphisms (ht1[AA]) was significantly associated with smaller areas of abdominal subcutaneous fat (p=0.003). We observed no significant associations between these UCP1 genetic polymorphisms and thigh fat areas, visceral fat areas, or blood biochemical profiles, suggesting that this polymorphism might differentially affect fat accumulation in different parts of the human body, even though further study is needed to elucidate the mechanism of it.