DNA POLYMORPHISMS IN THE ALPHA(2)-ADRENOCEPTOR 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. Skinf old thickness measurements and genetic analyses (Southern blot) were p erformed on 280 individuals (142 parents and 138 offsprings) from the Quebec Family Study. Using the association study design in unrelated a dults, women but not men carrying the 6.3-kb allele of an alpha(2A)-ad renoceptor/DraI RFLP had a significantly higher trunk to extremity ski nfold ratio (= sum of subscapular + suprailiac + abdominal skinfolds/s um of biceps + triceps + medial calf skinfolds) compared to women with out the allele (1.44 +/- 0.52 vs. 1.12 +/- 0.33; p<0.005 after adjustm ent for age, p<0.002 after adjustment for age and body mass index or f or age and subcutaneous fat). Using the sib-pair linkage procedure, a significant inverse relationship was found between the proportion of a lleles identical by descent shared by sibs at the alpha(2A) RFLP marke r 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 ind ex or for age and subcutaneous fat). For a beta 2-adrenoceptor/BanI RF LP, no significant association or linkage was found between fat distri bution 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-ab dominal fat in women, and that the alpha(2A)-adrenoceptor gene, or a l ocus in close proximity, may be linked to body fat distribution in hum ans independently of the overall level of fatness.