Department of Medical Genetics, Ajou University School of Medicine, Suwon, Republic of Korea.
Mol Genet Metab. 2013 Jan;108(1):95-101. doi: 10.1016/j.ymgme.2012.10.017. Epub 2012 Oct 24.
Emerging evidence has revealed a close relationship between obesity and osteoporosis. It was reported recently that conditional knockout of the Spry1 gene in mice adipocytes causes an increase in body fat and a decrease in bone mass, and that these phenotypes are rescued by Spry1 overexpression in adipose tissue. In this study, we investigated whether genetic variation in the human SPRY1 gene is associated with obesity-related phenotypes and/or osteoporosis in humans.
We performed a candidate gene association analysis between the four single nucleotide polymorphisms (SNPs) and 14 imputed SNPs in the SPRY1 gene and obesity-related traits and osteoporosis in a Korean women cohort (3013 subjects).
All four SPRY1 gene SNPs were significantly associated with either obesity-related traits or osteoporosis. The TGCC haplotype in the SRPY1 gene showed simultaneous association with an increased risk for obesity-related traits, percentage body fat (p=0.0087) and percentage abdominal fat (p=0.047), and osteoporosis (odds ratio=1.50; p=0.025) in the recessive genetic model.
Our results support a previous finding in conditional Spry1 gene knockout mice and suggest that the SPRY1 gene is an important genetic factor for determining the risk of both obesity and osteoporosis in humans.
新出现的证据表明肥胖症和骨质疏松症之间存在密切关系。最近有报道称，条件性敲除小鼠脂肪细胞中的 Spry1 基因会导致体脂肪增加和骨量减少，而脂肪组织中 Spry1 的过表达可以挽救这些表型。在这项研究中，我们研究了人类 SPRY1 基因中的遗传变异是否与肥胖相关表型和/或骨质疏松症有关。
我们在韩国女性队列（3013 名受试者）中，对 SPRY1 基因中的四个单核苷酸多态性（SNP）和 14 个推断的 SNP 与肥胖相关表型和骨质疏松症之间进行了候选基因关联分析。
所有四个 SPRY1 基因 SNP 均与肥胖相关表型或骨质疏松症显著相关。SRPY1 基因中的 TGCC 单倍型在隐性遗传模型中同时与肥胖相关表型、体脂肪百分比（p=0.0087）和腹部脂肪百分比（p=0.047）以及骨质疏松症（优势比=1.50；p=0.025）的风险增加相关。
我们的结果支持条件性 Spry1 基因敲除小鼠的先前发现，并表明 SPRY1 基因是决定人类肥胖和骨质疏松症风险的重要遗传因素。
