Abstract

The genes controlling long-term weight changes are largely unknown. The beta1 (beta1)-adrenoceptor gene contains two nonsynonomous single nucleotide polymorphisms (SNPs), Ser49Gly and Gly389Arg, that both are functional in human cell lines. We investigated the influence of these two SNPs on short- and long-term changes in body mass index (BMI) in a population-based cohort of 761 women who were examined during pregnancy in 1984-1985 and 15 y thereafter. At entry, no genotype effect on BMI was found. After 15 y, the BMI of women carrying the Gly49-genotype (25.3+/-0.3 kg/m(2)) was higher (P<0.005) than that of Ser49-women (24.4+/-0.2 kg/m(2)). Also, the BMI-increase over 15 y was higher (P=0.018) in Gly49-women (3.3+/-0.2 kg/m(2)) than in Ser49-women (2.8+/-0.1 kg/m(2)). The odds ratio for being overweight after 15 y having the Gly49-genotype was 1.6 (confidence interval 1.1-2.3, P=0.01). No effect of SNP 389 alone on BMI was found but there was a genotype-genotype interaction. Those carrying the Gly49-Gly389 combination increased their BMI about 0.7 kg/m(2) more than other combinations (P=0.025). No genotype effect on BMI changes during pregnancy for either SNP was found. Polymorphism of the beta1-adrenoceptor gene influences long-term weight gain and the incidence of adult-onset overweight in women.

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