The Arg64 allele of the β3-adrenoceptor gene but not the −3826G allele of the uncoupling protein 1 gene is associated with increased leptin levels in the Spanish population

To determine whether there are variations in leptin levels according to the β3-adrenoceptor (β3-AR) Trp64Arg and uncoupling protein 1 (UCP1) −3826A→G polymorphisms, given the regulatory role of catecholamines through the β3-AR in leptin production and the previously reported association of the UCP1 −3826A→G variant with obesity. A total of 160 men and 172 women randomly chosen from a nationwide population-based obesity cross-sectional survey in Spain were studied. Body mass index (BMI), waist-to-hip ratio (WHR), leptin, insulin, fasting and 2-hour post-glucose load glycemia, high-density lipoprotein (HDL)-, low-density lipoprotein (LDL)-, and total cholesterol, and triglyceride plasma levels were measured. β3-AR Trp64Arg and UCP1 −3826A→G genotypes were determined by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR). UCP1 −3826G allele frequency was higher in men than in women (0.31 v0.22, P= .015) and in obese women than in non-obese women (0.31 v0.17, P= .008). Women carriers of the Arg64 or the alleles also showed higher leptin levels than noncarriers. Multiple linear regression analysis showed that the Arg64 allele is associated with higher leptin levels after the adjustment for gender, age, WHR, and the degree of glucose tolerance. In conclusion, the β3-AR Trp64Arg polymorphism might have an impact on the mechanisms involved in leptin release from adipose tissue. Furthermore, our results agree with the previously reported association between UCP1 −3826G allele and obesity and point to a gender-related effect.