Peroxisome proliferator-activated receptor gamma polymorphism is related to peak bone mass: the JPOS study

Abstract

We analyzed 1,217 women to examine the effect of peroxisome proliferator-activated receptors gamma (PPARgamma) C161 --> T on bone status. Among 664 premenopausal women, the C161 --> T is associated with low bone mineral density (BMD) at the total hip and femoral neck. Moreover, the odds ratio for osteopenia or osteoporosis at the femoral neck was 1.98 for premenopausal CT/TT genotypes. The impact of PPARgamma on BMD has not been conclusively established. We examined if PPARgamma C161T polymorphism is associated with BMD and its change. We conducted a baseline survey in 1996 and a 10-year follow-up survey, Japanese Population-based Osteoporosis Study, with a sample population representative of Japanese women. Of these, 1,217 participants in the 1996 survey were analyzed cross-sectionally, while longitudinal analysis was performed on 563 women. A P value < 0.0042 (=0.05/12 for three menstrual statuses and four skeletal sites) was considered statistically significant after Bonferroni correction in multiple testing for cross-sectional analysis. The total hip and femoral neck BMDs were significantly higher for CC genotype than for CT/TT genotypes among 664 premenopausal women (P = 0.0020, P = 0.0022, respectively). Compared to the CC genotype, the odds ratio for osteopenia or osteoporosis (T-scores below -1) at the femoral neck was 1.98 for premenopausal CT/TT genotypes with statistical significance (P = 0.0041). Change of BMD at either skeletal site during the follow-up period was not significantly different for either menstrual status. We conclude that the PPARgamma C161T is associated with low peak bone mass.