Jiang X-Y, Chen Y, Xu L, Li X, Cao F-F, Li L, Lu M, Jin L, Wang X-F
Department of pharmacology, Tongji University School of Medicine, Shanghai, China.
Exp Clin Endocrinol Diabetes. 2010 Jun;118(6):388-91. doi: 10.1055/s-0029-1225613. Epub 2010 Feb 9.
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.
最近,在一项全基因组关联研究中发现,骨保护素(OPG)基因附近的两个单核苷酸多态性位点rs4355801以及低密度脂蛋白受体相关蛋白5(LRP5)基因中的rs3736228与高加索人的骨质疏松症及骨质疏松性骨折有关。在本研究中,我们调查了这两个单核苷酸多态性位点(rs4355801和rs3736228)与425名中国汉族受试者的骨密度(BMD)、全身T值以及代谢表型(如体重指数、血糖、甘油三酯和总胆固醇)之间的关联。我们观察到LRP5基因中的rs3736228与髋部骨密度、总骨密度及T值之间存在显著关联。随着风险T等位基因数量的增加,髋部骨密度、总骨密度及T值水平显著降低(p值分别为0.006、0.003和0.006)。在考虑性别和年龄因素后,这一发现仍然显著。我们还观察到样本中rs3736228与总胆固醇(CHO)水平之间存在显著关联。CC、CT和TT基因型的CHO水平分别为4.71、4.76和5.24(p = 0.031)。对于OPG基因的rs4355801,携带A等位基因拷贝的个体,其髋部骨密度、脊柱骨密度和总骨密度水平持续降低,但这些结果均无统计学意义。我们也未观察到上述两个多态性位点与中国汉族受试者的体重指数、血糖及甘油三酯水平之间存在显著关联。因此,我们的观察结果支持rs3736228与汉族受试者骨密度之间的关联。我们还首次提供证据表明,rs3736228的T等位基因会使一般汉族人群的总胆固醇水平升高。