The influence of IL6, COL1A1 and VDR gene polymorphisms on bone mineral density in Crohn's disease

Catherine E Todhunter ¹, Alison Sutherland-Craggs ¹, Sarah A Bartram ², Peter Donaldson ¹, Ann Daly ¹, Roger Francis ¹, John C Mansfield ³ and Nick P Thompson ^4*

¹ University of Newcastle upon Tyne, United Kingdom
² Newcastle upon Tyne Hospitals NHS Trust, United Kingdom
³ Royal Victoria Infirmary, United Kingdom
⁴ Freeman Hospital (Trust Headquarters), United Kingdom

^* To whom correspondence should be addressed. E-mail: nick.thompson{at}tfh.nuth.northy.nhs.uk.

Accepted 21 June 2005

Abstract

Background: Osteoporosis is an important cause of morbidity in patients with Crohn's disease. The pathogenesis of reduced bone mineral density (BMD) is multi-factorial. A range of genetic factors have been implicated in other populations of patients with osteoporosis.

Aim: To investigate the influence of interleukin-6 (IL6), collagen type 11 (COL1A1) and vitamin D receptor gene (VDR) single nucleotide polymorphisms (SNP) on bone mineral density in patients with Crohn's disease.

Patients: A cohort of 245 well characterised patients with Crohn's disease was recruited from the inflammatory bowel disease register at the Freeman Hospital and Royal Victoria Infirmary, Newcastle upon Tyne and the Queen Elizabeth Hospital, Gateshead.

Methods: Patients were genotyped for IL6 C-174G SNP, COL1A1 Sp1 binding site G T SNP, VDR Taq1 and Fok1 SNPs and CARD15 R702W, G908R and L1007fs SNPs. Bone mineral density (BMD) was measured at the lumbar spine (LSP) and hip using dual energy x-ray absorptiometry.

Results: 158 female, 87 male patients aged 24 to 70 years (mean 44 years) were recruited. There were no significant differences in the distribution of the tested SNPs when analysed for age, body mass index (BMI), pre/post-menopausal status, smoking or steroid use. 213 patients were genotyped for the IL6 SNP. LSP and total hip BMD was significantly lower in patients with GG genotype (48%) than CC genotype (15%), p=0.041, p=0.014. 180 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 genotype for the two VDR SNPs or CARD15 genotypes examined.

Conclusion: The IL6 and COL1A1 gene polymorphisms studied influence BMD in patients with Crohn's disease, but the particular VDR gene polymorphisms studied do not have a major effect.

Keywords: COL1A1 polymorphism, Crohn's disease, IL6 polymorphism, VDR polymorphism, bone mineral density

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