Ota N, Hunt S C, Nakajima T, Suzuki T, Hosoi T, Orimo H, Shirai Y, Emi M
Department of Molecular Biology, Institute of Gerontology, Nippon Medical School, Kawasaki, Japan.
Hum Genet. 1999 Sep;105(3):253-7. doi: 10.1007/s004390051097.
Osteopenia and osteoporosis are common human conditions considered to result from the interplay of multiple genetic and environmental factors. Twin and family studies have yielded strong correlations between levels of bone mass and a number of genetic factors. The genes involved could regulate metabolism, formation and resorption of bone, all processes that determine bone mass. We tested 192 sibling pairs of adult Japanese women from 136 families for genetic linkage between osteopenia and allelic variants of four candidate genes (interleukin-6, interleukin-6 receptor, calcium-sensing receptor, and matrix gla protein) using qualitative and quantitative methods, and using as genetic markers dinucleotide-repeat polymorphisms present in or near each of those loci. The interleukin-6 locus showed evidence of linkage to osteopenia analyzed as a qualitative trait, with mean allele sharing of 0.40 (P=0.0001) in discordant pairs and 0.55 (P=0.04) in concordant affected pairs. Variation at this locus was also linked to decreased bone mineral density measured as a quantitative trait (P=0.02). Analyses limited only to the post-menopausal women showed similar or even stronger results. No other locus among those tested showed any evidence of linkage by either method. The results provided strong evidence that genetic variation at the interleukin-6 locus affects regulation of bone mineral metabolism and confers risk for osteopenia and osteoporosis in adult women.
骨质减少和骨质疏松是常见的人类病症，被认为是多种遗传和环境因素相互作用的结果。双胞胎和家族研究表明，骨量水平与许多遗传因素之间存在很强的相关性。所涉及的基因可以调节骨的代谢、形成和吸收，而这些过程都决定了骨量。我们使用定性和定量方法，以存在于这四个候选基因（白细胞介素-6、白细胞介素-6受体、钙敏感受体和基质Gla蛋白）每个基因座或其附近的二核苷酸重复多态性作为遗传标记，对来自136个家庭的192对成年日本女性同胞进行了骨质减少与这四个候选基因的等位基因变体之间的遗传连锁测试。白细胞介素-6基因座显示出与作为定性性状分析的骨质减少存在连锁证据，在不一致的同胞对中平均等位基因共享率为0.40（P = 0.0001），在受影响的一致同胞对中为0.55（P = 0.04）。该基因座的变异也与作为定量性状测量的骨矿物质密度降低有关（P = 0.02）。仅对绝经后女性进行的分析显示出相似甚至更强的结果。在所测试的其他基因座中，没有任何一个基因座通过任何一种方法显示出连锁证据。这些结果提供了强有力的证据，表明白细胞介素-6基因座的遗传变异会影响骨矿物质代谢的调节，并使成年女性面临骨质减少和骨质疏松的风险。
