Kuipers A L, Zhang Y, Yu S, Kammerer C M, Nestlerode C S, Chu Y, Bunker C H, Patrick A L, Wheeler V W, Miljkovic I, Zmuda J M
Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA,
Osteoporos Int. 2014 Mar;25(3):905-12. doi: 10.1007/s00198-013-2517-0. Epub 2013 Oct 18.
We determined factors associated with serum sclerostin in 446 Afro-Caribbean family members. Age, weight, sex, diabetes and kidney function were associated with sclerostin. Sclerostin was heritable, and nine SNPs in the SOST gene region were associated with sclerostin. Variation in serum sclerostin is a heritable factor that is determined by both genetic and environmental factors.
Sclerostin, encoded by the SOST gene, is a Wnt inhibitor that regulates bone mineralization and is a candidate gene locus for osteoporosis. However, little is known about the genetic and non-genetic sources of inter-individual variation in serum sclerostin levels.
Serum sclerostin was measured in 446 Afro-Caribbean men and women aged 18+ from seven large, multigenerational families (mean family size, 64; 3,840 relative pairs). Thirty-six common single nucleotide polymorphisms (SNP) were genotyped within a 100 kb region encompassing the gene encoding sclerostin (SOST). Genetic and non-genetic factors were tested for association with serum sclerostin.
Mean serum sclerostin was 41.3 pmol/l and was greater in men than in women (P < 0.05). Factors associated with higher serum sclerostin were increased age and body weight, male sex, diabetes and decreased glomerular filtration rate, which collectively accounted for 25.4 % of its variation. Residual genetic heritability of serum sclerostin was 0.393 (P < 0.0001). Nine SNPs reached nominal significance with sclerostin. Three of those nine SNPs represented independent association signals (rs851056, rs41455049 and rs9909172), which accounted for 7.8 % of the phenotypic variation in sclerostin, although none of these SNPs surpassed a Bonferroni correction for multiple comparisons.
Serum sclerostin is a heritable trait that is also determined by environmental factors including age, sex, adiposity, diabetes and kidney function. Three independent common SNPs within the SOST region may collectively account for a significant proportion of the variation in serum sclerostin.
我们在446名非洲加勒比家庭成员中确定了与血清硬化蛋白相关的因素。年龄、体重、性别、糖尿病和肾功能与硬化蛋白有关。硬化蛋白具有遗传性，并且SOST基因区域中的9个单核苷酸多态性（SNP）与硬化蛋白相关。血清硬化蛋白的变异是一种由遗传和环境因素共同决定的可遗传因素。
由SOST基因编码的硬化蛋白是一种Wnt抑制剂，可调节骨矿化，是骨质疏松症的候选基因位点。然而，关于血清硬化蛋白水平个体间变异的遗传和非遗传来源知之甚少。
对来自7个大型多代家庭（平均家庭规模为64人；384个亲属对）的446名18岁及以上的非洲加勒比男性和女性进行血清硬化蛋白检测。在包含编码硬化蛋白（SOST）的基因的100 kb区域内对36个常见单核苷酸多态性（SNP）进行基因分型。测试遗传和非遗传因素与血清硬化蛋白的相关性。
血清硬化蛋白的平均水平为41.3 pmol/l，男性高于女性（P < 0.05）。与血清硬化蛋白水平升高相关的因素包括年龄增加、体重增加、男性性别、糖尿病和肾小球滤过率降低，这些因素共同解释了其变异的25.4%。血清硬化蛋白的残余遗传力为0.393（P < 0.0001）。9个SNP与硬化蛋白达到名义显著性。这9个SNP中的3个代表独立的关联信号（rs851056、rs41455049和rs9909172），它们占硬化蛋白表型变异的7.8%，尽管这些SNP均未超过多重比较的Bonferroni校正。
血清硬化蛋白是一种可遗传的性状，同时也由包括年龄、性别、肥胖、糖尿病和肾功能在内的环境因素决定。SOST区域内的3个独立常见SNP可能共同解释了血清硬化蛋白变异的很大一部分。
