Association of LPR5 polymorphism with bone mass density and cholesterol level in population of Chinese Han

Recently, two single nucleotide polymorphisms, rs4355801 near the osteoprotegerin (OPG) gene and rs3736228 in the low-density lipoprotein receptor-related protein 5 (LRP5) gene, were found to be associated with osteoporosis and osteoporotic fractures in Caucasians in a genome wide association study. In the present study, we investigated the association between these two SNPs (rs4355801 and rs3736228) and bone mass density (BMD), whole body T score and metabolic phenotypes (e. g., body mass index, glucose, triglyceride, and total cholesterol) in 425 Chinese Han subjects. We observed a significant association between rs3736228 in LRP5 and hip BMD, total BMD, and T score. The level of hip BMD, total BMD, and T score was significantly reduced with the number of at risk T alleles (p=0.006, p=0.003, and p=0.006, respectively). This finding was still significant after accounting for gender and age. We also observed a significant association between rs3736228 and total cholesterol (CHO) levels in our sample. The CHO levels of the CC, CT, and TT genotypes were 4.71, 4.76, and 5.24, respectively (p=0.031). For OPG rs4355801, the level of hip BMD, spine BMD, and total BMD was consistently reduced in persons with the copy of A allele, but none of these findings were statistically significant. We also did not observe a significant association between the above two polymorphisms and body mass index, glucose, and triglyceride levels in Chinese Han subjects. Thus, our observations support the association between rs3736228 and BMD in Han subjects. We also provide first evidence that the T allele of rs3736228 increases the total cholesterol level in a general Han population.