Leptin receptor genotype at Gln223Arg is associated with body composition, BMD, and vertebral fracture in postmenopausal Danish women
Leptin receptor genotype at Gln223Arg is associated with body composition, BMD, and vertebral fracture in postmenopausal Danish women
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DOI：
10.1359/jbmr.070114
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发表时间：
2007-04-01
影响因子：
6.2
通讯作者：
Blakemore, Alexandra I. F.
中科院分区：
文献类型：
--
作者：
Fairbrother, Una L.;Tanko, Laszlo B.;Blakemore, Alexandra I. F.
简介：非同义的单核苷酸多态性（SNPs）在人类LEPR基因已与肥胖症的一些研究，但一直没有大规模的研究，其影响骨密度和骨质疏松性骨折的风险在绝经后women.Materials和方法：我们进行了一项以人群为基础的研究1430名妇女。三个众所周知的非同义瘦素受体（LEPR）单核苷酸多态性（Lys 109 Arg，Gln 223 Arg，和Lys 656 Asn）进行基因分型的定性和定量关联分析。表型特征的主要利益是DXA措施的身体脂肪和瘦肉组织质量，骨密度，和放射学椎骨fractures.Results：Gln 223 Arg与椎骨骨折的风险（整体OR 1.76; OR吸烟者= 2.31; P = 0.0004），除了股骨颈和全髋关节的BMD（P = 0.036和0.008，分别）。杂合子携带者在这两个网站显示较低的BMD。Gln 223 Arg也与肥胖相关（总脂肪量p = 0.001）。对于肥胖症，在风险等位基因是G（导致精氨酸在位置223）。结论：LEPR的变化似乎有助于在丹麦绝经后妇女的BMD和骨折风险的变化，杂合子基因型与显性骨质疏松症的风险增加。需要进一步的研究来复制这些数据并澄清所涉及的机制。
Introduction: Nonsynonymous single nucleotide polymorphisms (SNPs) in the human LEPR gene have been associated with adiposity in a number of studies, but there have been no large-scale studies of their implications for BMD and osteoporotic fracture risk in postmenopausal women.Materials and Methods: We carried out a population-based study of 1430 women. Three well-known non-synonymous leptin receptor (LEPR) SNPs (Lys109Arg, Gln223Arg, and Lys656Asn) were genotyped for qualitative and quantitative association analysis. Phenotype characteristics of main interest were DXA measures of body fat and lean tissue mass, BMD, and radiographic vertebral fractures.Results: Gln223Arg associated with risk of vertebral fracture (overall OR 1.76; OR in smokers = 2.31; p = 0.0004), in addition to BMD of the femoral neck and total hip (p = 0.036 and 0.008, respectively). Heterozygote carriers showed lower BMD at both sites. Gln223Arg was also associated with adiposity (p = 0.001 for total fat mass). For adiposity, the at-risk allele was G (resulting in an arginine at position 223).Conclusions: Variation in LEPR seemed to contribute to the variation in BMD and fracture risk in Danish postmenopausal women; the heterozygous genotype was associated with increased risk of manifest osteoporosis. Further studies are needed to replicate these data and to clarify the mechanisms involved.