SP1 binding site polymorphism in the col1A1 gene is associated with BMD: The rotterdam study

Abstract

Vitamin D treatment in elderly populations has in recent years been shown to reduce hip fractures. The aim of the present study was to perform a longitudinal study of calcidiol (25 OH vitamin D) in a community based population and to analyze correlations to J risk factors for osteoporosis. PoPulation and methods. The study is a part of the geriatric and gerontological population studies in G6teborg, Sweden. A randomized population of men and women born 1901/02 has been investigated with regular intervals since 1970/71. Blood samples were taken in a standardized way and stored at -20 C. For this study 25 OH vitamin D was analyzed at the age of 85 (men n=41, women n=130) and 92 (men n=25, women n= 67) with a RIA assay. In 17 men and 47 women a longitudinal analysis was performed.Results. At the age of 85 the mean value of calcidiol for the whole population examined was 54.7 nmol/1 (SD 20.4) in men and 48.4 nmol/l (SD 19.9) in women. In 92-year-olds the values decreased to 40.9 nmol/l (SD 13.9) in men and 39.8 nmol/l (SD 17.1) in women, respectively. Among the population which was studied longitudinal calcidiol decreased in men from 51.5 nmol/l (SD 15.0) to 40.1 nmol/l (SD 16.0) and in women from 44.1 nmol/1 (SD 19.5) to 39.0 (SD 16,2), p<O.O1 and p<O.05, respectively. No seasonal variation was observed. There was a good correlation between calcidiol at 85 and 92 years of age (r= 0.45, p<O.O01). No correlation was found between calcidiol and bone mineral density (BMD) in calcaneus at 85 years of age (n=123) or betwee*~ BMD in femoral neck at 92 year of age (n=19). In 85-year-olds there was a significant correlation between calcidiol and free calcium in women (p<O.05) but not in men, No correlation was however found to PTH. Conclusion. A significant decrease in calcidiol was found between 85 and 92 years of age and calcidiol was significantly correlated to free calcium in 85-year-old women. In this random population, however, no correlation was found between calcidiol and BMD.

An Sp1 Binding Site Polymorphism in the COLIA1 Gene Predicts Osteoporotic Fractures in Both Men and Women

“…Individuals with the low bone density‐associated ss genotype were 10 times more frequent in the osteoporotic group (14.3%) when compared with the control group (1.4%), reflecting a relative risk of 11.83 for the presence of osteoporotic vertebral fracture in those with the rare ss genotype. The over‐representation of s alleles in osteoporotic patients from Denmark are consistent with those found in osteoporotic U.K. women 14 , 20 and in osteoporotic Dutch women, 21 suggesting that the COLIA1 polymorphism has potential clinical value as a predictor of osteoporotic vertebral fracture in diverse populations. A preliminary study by Hustmeyer et al published in abstract form 22 did not find any over‐representation of ss in the osteoporotic group.…”

“…Indeed, the lack of an association between COLIA1 genotype and BMD in the controls, which we found in this study, is in accordance with recent data, published in abstract form, which have shown no association between COLIA1 genotype and bone mass in certain populations 25–27 . Nonetheless, data from other large population‐based cohorts in The Netherlands 21 and France 26 has shown an association between COLIA1 genotype and BMD, while also showing that the effect is relatively small. Since the number of individuals studied here in the control and fracture groups was relatively small and comprised of both males and females, we may have had limited power to detect genotype differences in BMD.…”

Osteoporosis in chronic obstructive pulmonary disease

“…Some researchers have investigated the polymorphism of the genes encoding receptors for vitamin D or oestrogens and the genes for collagen type I or interleukin (IL)-6 (a cytokine involved in the differentiation of osteoclasts) [24,[26][27][28]. While there is still considerable controversy on the genetic determinism of osteoporosis [24,75], the most promising finding remains the identification of a polymorphism in the gene COLIA1 which encodes the type I collagen and mutations of this gene have been associated with a low BMD [29,30].…”