A1330V polymorphism of the low-density lipoprotein receptor-related protein 5 gene and bone mineral density in Japanese male workers.

OBJECTIVES: Both genetic and lifestyle factors have been shown to influence bone mineral density (BMD). We investigated the correlations between BMD and low-density lipoprotein receptor-related protein 5 (LRP5) A1330V (rs3736228) polymorphism, exercise, smoking, and alcohol intake in Japanese male workers.

METHODS: The subjects were 829 male employees (aged 20-59 years) of a large-scale integrated manufacturing facility in Japan. BMD was measured at the nondominant radius by dual-energy X-ray absorptiometry. Lifestyle information was obtained by a questionnaire at the same time, and genomic DNA was isolated from peripheral leukocytes.

RESULTS: Mean ± standard deviation (SD) BMD was 0.557 ± 0.059 g/cm(2). The genotype frequencies of LRP5 gene polymorphism were 51, 42, and 7% for AA, AV, and VV, respectively. Analysis of variance and post hoc Tukey test indicated that mean BMD was significantly lower in subjects with VV genotype than in those with AA genotype (0.540 ± 0.048 versus 0.562 ± 0.062 g/cm(2)). According to multiple linear regression analysis, LRP5 A1330V polymorphism was an independent determinant of BMD, after adjusting for age, body mass index (BMI), and lifestyle variables. Exercise (past or current) also influenced BMD.

CONCLUSIONS: These findings suggest that LRP5 A1330V polymorphism and exercise may influence BMD in Japanese male workers.