Nissen N, Madsen J S, Bladbjerg E M, Beck Jensen J E, Jørgensen N R, Langdahl B, Abrahamsen B, Brixen K
Department of Endocrinology, Odense University Hospital, University of Southern Denmark, Odense, 5000, Odense C, Denmark.
Calcif Tissue Int. 2009 Apr;84(4):276-85. doi: 10.1007/s00223-009-9219-9. Epub 2009 Feb 19.
Both osteoporosis and hip geometry are independently associated with fracture risk. There is a significant genetic contribution to the risk of osteoporosis, and evidence provided by twin studies has suggested that hip geometry may also in part be genetically programmed. Polymorphisms in a number of genes, including those coding for methylene-tetrahydrofolate reductase (MTHFR c.677C > T), the purinergic P2X(7) receptor (Glu496Ala and Ile568Asn), and the low-density lipoprotein receptor-related protein 5 (LRP5 exon 9 [c.266A > G]), have been associated with an increased fracture incidence and/or reduced bone mineral density (BMD). The aim of the present study was to test whether these polymorphisms influence hip structural geometry in perimenopausal women. The four polymorphisms were genotyped in 800 healthy recently perimenopausal women never using hormone replacement therapy. BMD of the femoral neck was measured using a Hologic QDR-2000 densitometer and femoral neck axis length, neck width, neck shaft angle, and femoral head diameter were measured from the screen images. Genotype frequencies were compatible with Hardy-Weinberg equilibrium. No significant differences between homozygotes for the minor allele and carriers of the common allele regarding parameters of hip geometry were demonstrated. According to the anthropometric characteristics of the subjects, only body height in the MTHFR TT genotype group was significantly different from the combined CT/CC genotype group (P < 0.05). The geometric dimensions of the proximal femur in perimenopausal women are not associated with the MTHFR c.677C > T, P2X(7) (Glu496Ala), P2X(7) (Ile568Asn), and LRP5 exon 9 (c.266A > G) polymorphisms.
骨质疏松症和髋部几何形态均独立与骨折风险相关。骨质疏松症风险存在显著的遗传因素，双生子研究提供的证据表明髋部几何形态在一定程度上也可能由基因决定。包括编码亚甲基四氢叶酸还原酶（MTHFR c.677C>T）、嘌呤能P2X(7)受体（Glu496Ala和Ile568Asn）以及低密度脂蛋白受体相关蛋白5（LRP5第9外显子[c.266A>G]）在内的多个基因的多态性，都与骨折发生率增加和/或骨密度（BMD）降低有关。本研究的目的是检验这些多态性是否会影响围绝经期女性的髋部结构几何形态。对800名从未使用过激素替代疗法的近期围绝经期健康女性进行了这四种多态性的基因分型。使用Hologic QDR - 2000骨密度仪测量股骨颈的骨密度，并从屏幕图像中测量股骨颈轴长、颈宽、颈干角和股骨头直径。基因型频率符合哈迪 - 温伯格平衡。在髋部几何形态参数方面，次要等位基因纯合子与常见等位基因携带者之间未显示出显著差异。根据受试者的人体测量特征，仅MTHFR TT基因型组的身高与CT/CC基因型组合组有显著差异（P<0.05）。围绝经期女性近端股骨的几何尺寸与MTHFR c.677C>T、P2X(7)（Glu496Ala）、P2X(7)（Ile568Asn）和LRP5第9外显子（c.266A>G）多态性无关。
