The effect of the beta(2) adrenoceptor gene Thr164Ile polymorphism on human adipose tissue lipolytic function

1 A rare beta (2)-adrenoceptor gene polymorphism, Thr164Ile, has been descr ibed that impairs receptor function when transfected into cell lines. We in vestigated whether the polymorphism influences native receptor function by studying lipolysis in freshly isolated subcutaneous fat cells from 236 appa rently healthy subjects. 2 Twelve subjects were heterozygous for the 164Ile variant. The fat cells o f Ile carriers displayed a 6 fold increase (P = 0.02) in the lipolytic EC50 of terbutaline (a selective beta (2)-adrenoceptor agonist), but no change in the lipolytic action of dobutamine (a selective beta (1)-adrcnoceptor ag onist), compared with the Thr carriers. Maximum adrenoceptor agonist stimul ated lipolysis did not differ between Thr and Ile carriers. 3 The influence of two other polymorphisms (Arg16Gly and Gln27Glu) in the b eta (2)-adrenoceptor gene was considered. Six 164Ile carriers also carried the 16Gly and 27Glu alleles. The latter combination occurred among 105 of t he 164Thr carriers. For the 16Gly27Glu subgroup, the EC50 of terbutaline wa s about 10 fold higher in 16Ile as than in 164Thr carriers (P = 0.02) but t here was no difference between genotypes in maximum terbutaline action. The re was no difference between groups in dobutamine action. 4 In conclusion, the 164Ile variant of the Bz-adrenoceptor is associated wi th a decreased native adipocyte receptor function, as evidenced by a marked increase in the half maximal effective concentration of the lipolytic acti on of a selective beta (2)-adrenoceptor agonist. This suggests that genetic variance in the beta (2)-adrenoceptor gene might be important for catechol amine function in humans, at least as far as adipocyte lipolysis is concern ed.