Braga V, Sangalli A, Malerba G, Mottes M, Mirandola S, Gatti D, Rossini M, Zamboni M, Adami S
Rheumatology Unit, Valeggio S/M, University of Verona, Italy.
Calcif Tissue Int. 2002 Jun;70(6):457-62. doi: 10.1007/s00223-001-1088-9. Epub 2002 May 27.
Osteoporosis is a disease characterized by low bone mineral density (BMD) and up to 80% of its variance is under genetic control. Although osteoporosis is more frequent in women, one-third of hip fractures also occur in men. Much information on genetic factors and bone density has been obtained in women, but only a few studies have been performed in osteoporotic men. We have evaluated the relationship between polymorphisms for several candidate genes such as vitamin D receptor (VDR), collagen type Ia1 (COLIA1), and calcitonin receptor (CTR) in a sample of unrelated Italian men (n = 253, mean age 58.41 +/- 15.64 SD). We found no significant differences in BMD when subjects were stratified for their VDR (BsmI and FokI) and COLIA1 genotypes. BMD both at the lumbar spine and at the femoral neck were associated with polymorphism of CTR gene. The CC genotype of CTR gene had the lowest BMD value (P <0.05 and P <0.01 at the spine and hip, respectively) and its prevalence was significantly over-represented in the subgroup of men with prior hip or vertebral fracture as compared with controls (P = 0.004% c2 = 11.10). The men with the CC genotype also showed significantly lower body mass index (BMI), serum sex hormone binding globulin (SHBG), estradiol, total alkaline phosphatase-(total AP) and bone alkaline phosphatase (bone AP) levels and significantly higher free androgen index (FAI). In conclusion, the polymorphism of CTR gene but not VDR and COLIA1 is associated with osteoporosis incidence and the levels of alkaline phosphatase and estradiol. The lower BMD in CC genotype is apparently associated in males with depressed bone formation and lower estradiol levels.
骨质疏松症是一种以骨矿物质密度（BMD）低为特征的疾病，其高达80%的变异受基因控制。虽然骨质疏松症在女性中更为常见，但三分之一的髋部骨折也发生在男性身上。关于女性遗传因素和骨密度的信息已经很多，但针对骨质疏松男性的研究却很少。我们在一组无亲缘关系的意大利男性样本（n = 253，平均年龄58.41 +/- 15.64标准差）中评估了几个候选基因的多态性之间的关系，这些基因包括维生素D受体（VDR）、I型胶原蛋白α1（COLIA1）和降钙素受体（CTR）。当根据VDR（BsmI和FokI）和COLIA1基因型对受试者进行分层时，我们发现骨密度没有显著差异。腰椎和股骨颈的骨密度均与CTR基因的多态性有关。CTR基因的CC基因型骨密度值最低（在脊柱和髋部分别为P <0.05和P <0.01），与对照组相比，在既往有髋部或椎体骨折的男性亚组中其患病率显著过高（P = 0.004，c2 = 11.10）。CC基因型的男性还表现出显著较低的体重指数（BMI）、血清性激素结合球蛋白（SHBG）、雌二醇、总碱性磷酸酶（总AP）和骨碱性磷酸酶（骨AP）水平，以及显著较高的游离雄激素指数（FAI）。总之，CTR基因而非VDR和COLIA1的多态性与骨质疏松症的发生率以及碱性磷酸酶和雌二醇水平有关。在男性中，CC基因型较低的骨密度显然与骨形成受抑制和雌二醇水平较低有关。
