Husted L B, Harsløf T, Gonzalez-Bofill N, Schmitz A, Carstens M, Stenkjaer L, Langdahl B L
Department of Endocrinology and Metabolism, Aarhus University Hospital, Tage-Hansens Gade 2, 8000 Aarhus C, Denmark.
Calcif Tissue Int. 2009 Feb;84(2):85-96. doi: 10.1007/s00223-008-9199-1. Epub 2008 Dec 13.
Osteoporosis is a common age-related disease with a strong genetic influence. COLIA1 is one of the most extensively studied candidate genes and has consistently been associated with BMD and fracture. We examined the effects of the polymorphisms -1997G>T, -1663indelT, and +1245G>T and their haplotypes on vertebral fractures and bone mineral density (BMD) in a case-control study comprising 462 osteoporotic patients and 336 controls. The -1663indelT polymorphism was associated with a decreased lumbar spine (ls) BMD, 0.75 +/- 0.14 g/cm(2), in individuals with the del/del genotype versus 0.83 +/- 0.18 and 0.85 +/- 0.18 g/cm(2) in individuals with the ins/del and ins/ins genotypes, respectively (p = 0.02). The T-allele of the +1245G>T polymorphism, which was in strong linkage disequilibrium (LD) with -1663indelT, was also associated with a decreased lsBMD (p = 0.02). -1997G>T was not significantly associated with lsBMD. The three most common haplotypes accounted for 98.5% of the alleles. Individuals with one or two copies of haplotype 1 (-1997G/-1663ins/+1245G) had a significantly higher lsBMD, 0.84 +/- 0.18 and 0.85 +/- 0.15 g/cm(2), respectively, versus 0.78 +/- 0.15 g/cm(2) in noncarriers (p = 0.01). Individuals with two copies of haplotype 2 (-1997G/-1663del/+1245T) had a significantly lower lsBMD, 0.76 +/- 0.14 g/cm(2), versus 0.85 +/- 0.18 and 0.82 +/- 0.18 g/cm(2), respectively, in individuals with zero or one copy (p = 0.03). The odds ratio for vertebral fracture in individuals carrying the variant T-allele of the -1997G>T polymorphism was 1.49 (CI, 1.03-2.16; p = 0.03). Logistic regression revealed that this effect was partly independent of BMD. In conclusion, the -1663del and +1245T alleles influence BMD negatively, whereas the -1997T-allele has a minor effect on BMD but increases the risk of vertebral fractures. These findings are in agreement with functional studies showing that these polymorphisms influence gene expression.
骨质疏松症是一种常见的与年龄相关的疾病，具有很强的遗传影响。COLIA1是研究最为广泛的候选基因之一，一直与骨密度（BMD）和骨折相关。在一项包含462例骨质疏松症患者和336例对照的病例对照研究中，我们检测了-1997G>T、-1663indelT和+1245G>T多态性及其单倍型对椎体骨折和骨密度（BMD）的影响。-1663indelT多态性与腰椎（ls）BMD降低有关，del/del基因型个体的腰椎BMD为0.75±0.14g/cm²，而ins/del和ins/ins基因型个体的腰椎BMD分别为0.83±0.18g/cm²和0.85±0.18g/cm²（p = 0.02）。与-1663indelT处于强连锁不平衡（LD）状态的+
