Abstract
Introduction: We have examined the association of bone mineral density of patients with inflammatory
bowel disease with a polymorphism in the gene encoding the vitamin D receptor. The
thymine/cytosine (T/C) polymorphism in the first of two start codons can be defined
by a restriction fragment length polymorphism using the restriction endonuclease FokI.
Vitamin D receptor alleles containing the polymorphism have been denoted by f and
alleles lacking the site by F. Methods: We report on an association analysis of a basic population of 244 caucasian patients
with Crohn's disease. We have genotyped the FokI polymorphism of the VDR in these
patients and associated the genotype with the bone mineral density of the lumbar spine
and the femoral neck. Results: In the cohort 42 % of the patients were scored FF homozygous, 43.7 % Ff heterozygous,
and 14.3 % ff homozygous. 14.4 % of the FF patients, 18.8 % of the Ff patients, and
9.7 % of the ff patients had osteoporosis of the lumbar spine and 21.25 % of the FF
patients, 25.3 % of the Ff patients, and 18.5 % of the ff patients had osteoporosis
of the femoral neck. In this cohort no association between the genotype and the bone
mineral density in the group as a whole nor when separated according to sex or age
was found. Conclusions: In summary in our cohort no association of the FokI polymorphism and the BMD of the
lumbar spine and femoral neck in patients with inflammatory bowel disease was found.
Key words
FokI - inflammatory bowel disease - osteoporosis - vitamin D receptor
References
- 1
Abitol V, Roux C, Chaussade S, Guillemant S, Kolta S, Dougados M.
Metabolic bone assessment in patients with inflammatory bowel disease.
Gastroenterology.
1995;
108
417-422
- 2
Ames S K, Ellis K J, Gunn S K, Copeland S K, Abrams S A.
Vitamin D receptor gene FokI polymorphism predicts calcium absorption and bone mineral
density in children.
J Bone Miner Res.
1999;
14
740-746
- 3
Andreassen H, Rungby J, Dahlerup J F, Mosekilde J F.
Inflammatory bowel disease and osteoporosis.
Scand J Gastroenterol.
1997;
32
1247-1255
- 4
Ardizzone S, Bollani M, Bevilaqua G, Manzionna G, Baldi G, Vago T, Bianchi Porro G.
Prevalence of Fok I vitamin D receptor gene polymorphism among patients with inflammatory
bowel disease: a case control study.
Gut.
1999;
45 (Suppl V)
A 17.07
- 5
Baker A R, McDonnell D P, Hughes M, Crisp T M, Mangelsdorf D J, Haussler M R, Pike J W,
Shine J, O'Malley B W.
Cloning and expression of full-length cDNA encoding human vitamin D receptor.
Proc Natal Acad Sci.
1988;
85
3294-3298
- 6
Bernstein C N, Seeger L L, Anton P A, Artinian L, Geffrey S, Goodman W, Belin T R,
Shanahan F.
A randomized, placebo-controlled trial of calcium supplementation for decreased bone
density in corticosteroid-using patients with inflammatory bowel disease: a pilot
study.
Aliment Pharmacol Ther.
1996;
10
777-786
- 7
Bischoff S C, Herrmann A, Göke M, Manns M, Abbate R, zur Mühlen von A, Brabant G.
Altered bone metabolism in inflammatory bowel disease.
Am J Gastroenterol.
1997;
92
1157-1163
- 8
Bjarnason I, Macpherson A, Mackintosh C, Buxton T M, Forgacs I, Moniz C.
Reduced bone density in patients with inflammatory bowel disease.
Gut.
1997;
40
228-233
- 9
Compston J E, Judd D, Crawley E O, Evans W D, Evans C, Church H A, Reid E M, Rhodes J.
Osteoporosis in patients with inflammatory bowel disease.
Gut.
1987;
28
410-415
- 10
Eccleshall T R, Garnero P, Gross C, Delmas P D, Feldman D.
Lack of correlation between start codon polymorphism of the vitamin D receptor gene
and bone mineral density in premenopausal French women: the OFELY study.
J Bone Miner Res.
1998;
13
31-35
- 11
Ferrari S, Rizzoli R, Maenen D, Slosman D, Bonjour J P.
Vitamin D receptor gene start codon polymorphism (FokI) and bone mineral density:
interaction with age, dietary calcium, and 3′-end region polymorphisms.
J Bone Miner Res.
1998;
13
925-930
- 12
Gennari L, Becherini L, Mansani R, Masi L, Falchetti A, Morelli A, Colli E, Gonnelli S,
Cepollaro C, Brandi M L.
FokI polymorphism at the translation initiation site of the vitamin D receptor gene
predicts bone mineral density and vertebral fractures in postmenopausal Italian women.
J Bone Miner Res.
1999;
14
1379-1386
- 13
Ghosh S, Cowen S, Hannan W JFA.
Low bone mineral density in Crohn's disease but not in ulcerative colitis.
Gastroenterology.
1994;
107
1031-1039
- 14
Gross C, Eccleshall T R, Malloy P J, Villa M L, Marcus R, Feldman D.
The presence of a polymorphism at the translation initiation site of the vitamin D
receptor gene is associated with low bone mineral density in postmenopausal Mexican-American
women.
J Bone Miner Res.
1996;
11
1850-1855
- 15
Gross C, Krishnan A, Malloy P, Eccleshall T R.
The vitamin D receptor gene start codon polymorphism: a functional analysis of FokI.
J Bone Miner Res.
1998;
13
1691-1699
- 16
Harris S S, Eccleshall T R, Gross C, Dawson-Hughes B, Feldman D.
The vitamin D receptor start codon polymorphism (FokI) and bone mineral density in
premenopausal American black and white women.
J Bone Miner Res.
1997;
12
1043-1048
- 17
Hustmyer F, Peacock M, Hui S, Johnston C C, Christian J.
Bone mineral density in relation to polymorphism at the vitamin D receptor gene locus.
J Clin Invest.
1994;
94
2130-2134
- 18
Lucotte G, Mercier G BA.
The vitamin D receptor FokI start codon polymorphism and bone mineral density in osteoporotic
postmenopausal French women.
Clin Genet.
1999;
56
221-224
- 19
Morrison N A, Yeoman R, Kelly P J, Eisman J A.
Contribution of trans-acting factor alleles to normal physiological variability: vitamin
D receptor gene polymorphisms and circulating osteocalcin.
Proc Nat Acad Sci.
1992;
89
6665-6669
- 20
Morrison N A, Qi J C, Tokita A, Kelly P J, Crofts L, Nguyen T V, Sambrook P N, Elsman J A.
Prediction of bone density from vitamin D receptor alleles.
Nature.
1994;
367
284-287
- 21
Scharla S H, Minne H W, Lempert U G, Leidig G, Hauber M, Raedsch R, Ziegeler R.
Bone mineral density and calcium regulating hormones in patients with inflammatory
bowel disease (Crohn's disease and ulcerative colitis).
Exp Clin Endocrinol.
1994;
102
44-49
- 22
Vos de M, Keyser de F, Ielants H, Ubelier C, Eys E.
Review article: bone and joint diseases in inflammatory bowel disease.
Aliment Pharmacol Ther.
1998;
12
397-404
Dr. N. Bregenzer
Department of Internal Medicine I
University of Regensburg
93042 Regensburg
Germany
Telefon: + 499419447001
Fax: + 49 94 19 44 70 02
eMail: nicole.bregenzer@klinik.uni-regensburg.de
