title: Bone Metabolism and the c.-223C > T Polymorphism in the 5'UTR Region of the Osteoprotegerin Gene in Patients with Inflammatory Bowel Disease.
abstract: Osteoporosis is more frequent in inflammatory bowel disease (IBD) patients. A reduction in bone mineral mass in these individuals is caused not only by inflammatory processes in the bowel, because osteoporosis occurs already in very young IBD patients and in newly diagnosed individuals who have not yet undergone any pharmacological treatment. One of individual determinants of the bone turnover parameters is osteoprotegerin (OPG) encoded by the TNFRSF11B gene. The c.-223C > T polymorphism in this gene has been extensively studied in post-menopausal osteoporosis patients. However, no such studies exist for osteoporosis related to IBD. The aim of our study was to determine whether the c.-223C > T (rs2073617) polymorphism in the 5'UTR region of the gene encoding osteoprotegerin is a functional polymorphism which may change the gene expression and resulting OPG levels, and so be associated with osteopenia and osteoporosis, and impaired bone metabolism in Crohn's disease and ulcerative colitis patients. Our study included 198 IBD patients and 41 healthy controls. Lumbar spine and femoral neck bone mineral density, T-score, Z-score as well as OPG, RANKL, vitamin D, calcium and interleukin 4 and 10 concentrations were determined for all study subjects. Genotyping of the TNFRSF11B polymorphic site was performed by restriction fragment length polymorphism technique. Statistical analyses were conducted using Statistica software. Odds ratios, 95 % confidence intervals, and P values were calculated using the HWE calculator. Our results did not allow determining an unequivocal association between the polymorphic variants of the TNFRSF11B 5'UTR region and a susceptibility to osteoporosis in IBD patients. We have shown, however, that the c.-223T allele was twice as more frequent in Crohn's disease (CD) patients than among controls (OR = 1.99, P value = 0.009). Interestingly, average osteoprotegerin levels in CD patients did not significantly differ from those in controls, whereas in ulcerative colitis patients, OPG levels were significantly lower. We have concluded that low OPG levels may be associated with osteoporosis in ulcerative colitis, but it is not correlated with the c.-223C > T polymorphism in the TNFRSF11B gene. In CD patients, in turn, we observed increased RANKL levels. Our observations confirm different pathogeneses of Crohn's disease and ulcerative colitis as well as different molecular backgrounds of osteoporosis associated with these two diseases.
authors.affiliation: Department of Gastroenterology, Human Nutrition and Internal Diseases, Poznań University of Medical Sciences, Przybyszewskiego 49, 60-355, Poznan, Poland. krela@op.pl.
authors.forename: Iwona
authors.identifier: 0000-0003-0173-5431
authors.initials: I
authors.lastname: Krela-Kaźmierczak
authors.affiliation: Institute of Human Genetics, Polish Academy of Sciences, Strzeszyńska 32, 60-479, Poznan, Poland. m.kaczmarekrys@gmail.com.
authors.forename: Marta
authors.initials: M
authors.lastname: Kaczmarek-Ryś
authors.affiliation: Department of Gastroenterology, Human Nutrition and Internal Diseases, Poznań University of Medical Sciences, Przybyszewskiego 49, 60-355, Poznan, Poland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Szymczak
authors.affiliation: Department of Computer Science and Statistics, University of Medical Sciences, Poznan, Poland.
authors.forename: Michał
authors.initials: M
authors.lastname: Michalak
authors.affiliation: Institute of Human Genetics, Polish Academy of Sciences, Strzeszyńska 32, 60-479, Poznan, Poland.
authors.forename: Marzena
authors.initials: M
authors.lastname: Skrzypczak-Zielińska
authors.affiliation: Department of Biochemistry and Biotechnology, University of Life Sciences in Poznań, Poznan, Poland.
authors.forename: Natalia
authors.initials: N
authors.lastname: Drwęska-Matelska
authors.affiliation: Department of Family Medicine, University of Medical Sciences, Poznan, Poland.
authors.forename: Michalina
authors.initials: M
authors.lastname: Marcinkowska
authors.affiliation: Department of Gastroenterology, Human Nutrition and Internal Diseases, Poznań University of Medical Sciences, Przybyszewskiego 49, 60-355, Poznan, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Eder
authors.affiliation: Department of Gastroenterology, Human Nutrition and Internal Diseases, Poznań University of Medical Sciences, Przybyszewskiego 49, 60-355, Poznan, Poland.
authors.forename: Lilianna
authors.initials: L
authors.lastname: Łykowska-Szuber
authors.affiliation: Department of Laboratory Diagnostics, University of Medical Sciences, Poznan, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Wysocka
authors.affiliation: Department of Gastroenterology, Human Nutrition and Internal Diseases, Poznań University of Medical Sciences, Przybyszewskiego 49, 60-355, Poznan, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Linke
authors.affiliation: Institute of Human Genetics, Polish Academy of Sciences, Strzeszyńska 32, 60-479, Poznan, Poland.|Department of Biochemistry and Biotechnology, University of Life Sciences in Poznań, Poznan, Poland.
authors.forename: Ryszard
authors.initials: R
authors.lastname: Słomski
mesh_terms: D020121:5' Untranslated Regions; D000328:Adult; D001842:Bone and Bones / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000150:complications* / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000209:etiology*; D053244:Osteoprotegerin / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: D020121:5' Untranslated Regions; D053244:Osteoprotegerin; C506030:TNFRSF11B protein, human
keywords: Inflammatory bowel disease; Osteoporosis; Osteoprotegerin; TNFRSF11B gene polymorphism