Marshfield Clinic, Department of Medical Genetic Services, 1000 North Oak Avenue, Marshfield, WI 54449, USA.
Osteoporos Int. 2010 Mar;21(3):467-77. doi: 10.1007/s00198-009-0981-3. Epub 2009 Jun 9.
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.
在一项针对绝经后骨质疏松女性和骨密度正常的对照组的队列研究中，发现白细胞介素 6（IL6）-634G>C（rs1800796）启动子区域的 C 等位基因与骨质疏松症有关。脂蛋白受体相关蛋白 5（LRP5）基因仅在吸烟者中显示 C135242T C/T 等位基因与骨质疏松症之间存在关联，提示环境相互作用的作用。
在基于人群的队列中进行了一项嵌套病例对照研究，以评估吸烟、他汀类药物使用、遗传多态性以及这些因素的单向相互作用对绝经后妇女骨质疏松症发展的相对影响。
对来自同质白种人群的骨质疏松症病例（n=309）和骨密度正常的对照组（n=293）进行了维生素 D 受体基因、雌激素受体 1、胶原 1 型α1、IL6、转化生长因子β、载脂蛋白 E 和 LRP5 基因的 14 个单核苷酸多态性（SNP）的基因分型。根据已知的功能后果或先前的关联证据选择 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。
病例与对照组在体重指数、年龄和吸烟方面存在差异，但与他汀类药物使用无关。在调整年龄后，IL6-634G>C(rs1800796)等位基因与骨质疏松症相关（CC+CG 基因型的比值比（OR）为 2.51，p=0.0047）），独立于他汀类药物使用或吸烟状态。在吸烟分层后，发现 LRP5 C135242T(rs545382)与骨质疏松症之间存在关联（吸烟者 CT 等位基因的比值比为 2.8，p=0.03）），提示存在潜在的环境相互作用。
证据表明，IL6 和 LRP5 中的遗传变异在赋予白种女性骨质疏松症风险方面发挥作用，后者仅在吸烟者中表现出来。
