DNA polymorphisms in the alpha 2- and beta 2-adrenoceptor genes and regional fat distribution in humans: association and linkage studies.

The aim of this study was to investigate the relationships between DNA restriction fragment length polymorphisms (RFLP) in the alpha 2- and beta 2-adrenoceptor genes and body fat distribution in humans. Skinfold thickness measurements and genetic analyses (Southern blot) were performed on 280 individuals (142 parents and 138 offsprings) from the Québec Family Study. Using the association study design in unrelated adults, women but not men carrying the 6.3-kb allele of an alpha 2A-adrenoceptor/DraI RFLP had a significantly higher trunk to extremity skinfold ratio (= sum of subscapular+suprailiac+abdominal skinfolds/sum of biceps+triceps+medial calf skinfolds) compared to women without the allele (1.44 +/- 0.52 vs. 1.12 +/- 0.33; p < 0.005 after adjustment for age, p < 0.002 after adjustment for age and body mass index or for age and subcutaneous fat). Using the sib-pair linkage procedure, a significant inverse relationship was found between the proportion of alleles identical by descent shared by sibs at the alpha 2A RFLP marker locus and the squared differences of the trunk to extremity skinfold ratio (p = 0.02 after adjustment for age or for age and body mass index or for age and subcutaneous fat). For a beta 2-adrenoceptor/BanI RFLP, no significant association or linkage was found between fat distribution indicators and the marker. These results suggest that alpha 2A-adrenoceptor gene variability detected with DraI is associated with a relative subcutaneous fat pattern favoring accumulation of truncal-abdominal fat in women, and that the alpha 2A-adrenoceptor gene, or a locus in close proximity, may be linked to body fat distribution in humans independently of the overall level of fatness.