Todhunter C E, Sutherland-Craggs A, Bartram S A, Donaldson P T, Daly A K, Francis R M, Mansfield J C, Thompson N P
Department of Medicine, Freeman Hospital, High Heaton, Newcastle Upon Tyne, NE7 7DN, UK.
Gut. 2005 Nov;54(11):1579-84. doi: 10.1136/gut.2005.064212. Epub 2005 Jul 11.
Osteoporosis is an important cause of morbidity in patients with Crohn's disease. The pathogenesis of reduced bone mineral density (BMD) is multifactorial. A range of genetic factors have been implicated in other populations of patients with osteoporosis.
To investigate the influence of interleukin 6 (IL-6), collagen type 1alpha1 (COL1A1), and vitamin D receptor gene (VDR) single nucleotide polymorphisms (SNP) on BMD in patients with Crohn's disease.
A cohort of 245 well characterised patients with Crohn's disease were recruited from the inflammatory bowel disease register at the Freeman Hospital and Royal Victoria Infirmary, Newcastle upon Tyne, and the Queen Elizabeth Hospital, Gateshead, UK.
Patients were genotyped for IL-6 C-174G SNP, COL1A1 Sp1 binding site G T SNP, VDR Taq1, and Fok1 SNPs, and CARD15 R702W, G908R, and L1007fs SNPs. BMD was measured at the lumbar spine (LSP) and hip using dual energy x ray absorptiometry.
A total of 158 female and 87 male patients, aged 24-70 years (mean 44), were recruited. There were no significant differences in the distribution of the tested SNPs when analysed for age, body mass index, pre/post-menopausal status, smoking, or steroid use. Two hundred and thirteen patients were genotyped for the IL-6 SNP. LSP and total hip BMD was significantly lower in patients with the GG genotype (48%) than the CC genotype (15%) (p = 0.041, p = 0.014). One hundred and eighty patients were genotyped for the COL1A1 SNP. There was no significant difference in BMD at LSP. Hip BMD was significantly lower in heterozygous patients compared with homozygous wild-types (p = 0.034). There were no significant differences in BMD between genotypes for the two VDR SNPs or the CARD15 genotypes examined.
IL-6 and COL1A1 gene polymorphisms influence BMD in patients with Crohn's disease but the particular VDR gene polymorphisms studied do not have a major effect.
骨质疏松症是克罗恩病患者发病的重要原因。骨矿物质密度（BMD）降低的发病机制是多因素的。一系列遗传因素与其他骨质疏松症患者群体有关。
研究白细胞介素6（IL-6）、1α1型胶原蛋白（COL1A1）和维生素D受体基因（VDR）单核苷酸多态性（SNP）对克罗恩病患者骨密度的影响。
从英国泰恩河畔纽卡斯尔的弗里曼医院和皇家维多利亚医院以及盖茨黑德的伊丽莎白女王医院的炎症性肠病登记处招募了245名特征明确的克罗恩病患者。
对患者进行IL-6 C-174G SNP、COL1A1 Sp1结合位点G>T SNP、VDR Taq1和Fok1 SNP以及CARD15 R702W、G908R和L1007fs SNP的基因分型。使用双能X线吸收法测量腰椎（LSP）和髋部的骨密度。
共招募了158名女性和87名男性患者，年龄在24至70岁之间（平均44岁）。在按年龄、体重指数、绝经前/后状态、吸烟或使用类固醇进行分析时，所检测的SNP分布没有显著差异。对213名患者进行了IL-6 SNP基因分型。GG基因型（48%）患者的LSP和全髋骨密度显著低于CC基因型（15%）患者（p = 0.041，p = 0.014）。对180名患者进行了COL1A1 SNP基因分型。LSP处的骨密度没有显著差异。杂合子患者的髋部骨密度显著低于纯合野生型患者（p = 0.034）。所检测的两种VDR SNP或CARD15基因型之间的骨密度没有显著差异。
IL-6和COL1A1基因多态性影响克罗恩病患者的骨密度，但所研究的特定VDR基因多态性没有主要影响。
