Association of -3826 G variant in uncoupling protein-1 with increased BMI in overweight Australian women

Aims/hypothesis. To determine whether genetic variation in uncoupling protein-1 (UCP-1) is associated with obesity or obesity-related risk factors in overweight women. Methods. We genotyped 526 overweight/obese women (mean body mass index 34.1 kg/m², range 25.0 to 47.5 kg/m²) for the -3826 A → G uncoupling protein-1 polymorphism. Of the 526 women genotyped 144 had fasting blood samples analysed for glucose and lipid measurements. Results. The -3826 G allele was found with a frequency of 0.23 and was associated with higher BMI (p = 0.02). A higher frequency of this polymorphism (0.33) was found in subjects with Type II (non-insulin-dependent) diabetes mellitus (p = 0.02), though adjustment for BMI weakened this significance (p = 0.06). The -3826 G variant was associated with increased fasting glucose (p = 0.01). This was, however, a result of a greater proportion of women with Type II diabetes also having the G variant (p = 0.10, adjusted for Type II diabetes). The -3826 G variant of uncoupling protein-1 did not have an effect on other metabolic variables associated with obesity. Conclusion/interpretation. In overweight Australian women the -3826 G variant of UCP-1 increased the susceptibility to obesity indicating that UCP-1 could be involved in weight regulation.