To investigate the influence of lipoprotein lipase (LPL) Ser447Stop and β1-adrenergic receptor (ADRB1) Arg389Gly gene polymorphisms, individually and in combination, on obesity from childhood to adulthood.Design and subjects:
A community-based cohort of 1331 subjects (30% black and 70% white subjects) was followed over an average period of 23 years from childhood (age range: 4-17 years) to adulthood (age range: 18-44 years).Measurement:
Body mass index (BMI, kg/m2) and LPL Ser447Stop and the ADRB1 Arg389Gly genotypes.Results:
The frequency of the ADRB1 Gly389 allele was 0.25 in white subjects vs 0.39 in black subjects (P<0.001); 0.08 vs 0.05 (P=0.280) for the LPL Stop447 allele. There was no association between the LPL Stop447 allele and BMI among white and black subjects either in childhood and adulthood levels or annual change from childhood to adulthood. The ADRB1 Gly389 allele was associated with lower BMI only in black adults (P=0.017). Further, the interaction effect of the LPL Stop447 allele and ADRB1 Gly389 allele on adult BMI or its annual change was significant in white subjects and in the total sample (P=0.03-0.006). Childhood values tended to show a similar trend. Having both ADRB1 Gly389 allele and LPL Stop447 allele was associated with 71% (95% confidence interval: 26-89%) less odds for developing obesity from childhood to adulthood after adjusting for age, race, sex, and childhood BMI.Conclusion:
While Gly389 allele of the ADRB1 gene lowers obesity in black subjects, this allele in conjunction with Stop447 allele of the LPL gene lowers obesity in adults and attenuates the development of obesity from childhood to adulthood. These findings underscore the importance of gene-gene interaction in the assessment of genetic influences on complex traits such as obesity.