The role of cigarette smoking and statins in the development of postmenopausal osteoporosis: a pilot study utilizing the Marshfield Clinic Personalized Medicine Cohort
The role of cigarette smoking and statins in the development of postmenopausal osteoporosis: a pilot study utilizing the Marshfield Clinic Personalized Medicine Cohort
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DOI：
10.1007/s00198-009-0981-3
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发表时间：
2010-03-01
影响因子：
4
通讯作者：
Ghebranious, N.
中科院分区：
文献类型：
--
作者：
Giampietro, P. F.;McCarty, C.;Ghebranious, N.
在一组绝经后骨质疏松症女性和骨密度正常的对照组中，白介素6(IL6)-634G和C(Rs1800796)C等位基因与骨质疏松症相关。脂蛋白受体相关蛋白5(LRP5)基因C135242T C/T等位基因与绝经后妇女骨质疏松症的相关性研究表明，C135242T等位基因与骨质疏松症之间存在一定的环境交互作用。在人群队列中进行了一项嵌套病例对照研究，以评估吸烟、他汀类药物的使用、遗传多态以及这些因素的单向交互作用对绝经后妇女骨质疏松症发病的相对影响。对维生素D受体基因、雌激素受体1、胶原1α1、白介素6、转录生长因子β、载脂蛋白E、309例骨质疏松症患者和293例骨密度正常的高加索人群进行了LRP5基因检测。根据已知的功能结果或先前的关联证据来选择SNP，并使用基质辅助激光解吸电离飞行时间技术进行基因分型。原因与对照相比，与体重指数、年龄和吸烟有关，但与他汀类药物的使用无关。调整年龄后，IL6-634G>；C(Rs1800796)等位基因与骨质疏松有关联(CC+CG的优势比(OR)=2.51，p=0.0047)，与他汀类药物的使用或吸烟状况无关。在吸烟的分层上，出现了与LRP5C135242T(Rs545382)和骨质疏松症(吸烟者CT等位基因的OR为2.8，p=0.03)的关联，暗示了潜在的环境交互作用。证据表明，IL6和LRP5的基因变异在高加索女性患骨质疏松症的风险中起作用，而后者仅在吸烟者中表现出来。
A cohort of postmenopausal osteoporotic females and controls with normal bone mineral density, the interleukin 6 (IL6) -634G > C (rs1800796) C allele of the promoter region showed association with osteoporosis. The lipoprotein receptor-related protein 5 (LRP5) gene showed association between C135242T C/T alleles and osteoporosis only in smokers, suggesting a role for environmental interaction.A nested case-control study within a population-based cohort was undertaken to assess the relative impact of cigarette smoking, statin use, genetic polymorphisms, and one-way interaction of these factors on development of osteoporosis in postmenopausal women.Genotyping of 14 single-nucleotide polymorphisms (SNPs) corresponding to vitamin D receptor gene, estrogen receptor 1, collagen type 1 alpha 1, IL6, transcription growth factor beta, apolipoprotein E, and LRP5 genes was performed in cases (n = 309) with osteoporosis and controls (n = 293) with normal bone mineral density drawn from a homogeneous Caucasian population. SNPs were chosen based on known functional consequences or prior evidence for association and genotyped using matrix-assisted laser desorption ionization time-of-flight technology.Cases differed from controls relative to body mass index, age, and smoking but not statin use. After adjusting for age, the IL6 -634G > C (rs1800796) allele showed association with osteoporosis (odds ratio (OR) for CC + CG = 2.51, p = 0.0047)), independent of statin use or smoking status. On stratification for smoking, association with LRP5 C135242T (rs545382) and osteoporosis emerged (OR 2.8 in smokers for CT alleles, p = 0.03)), suggestive of potential environmental interaction.Evidence suggested a role for genetic variation in IL6 and LRP5 in conferring risk for osteoporosis in Caucasian women, with the latter manifest only in smokers.