Association analysis of vitamin D receptor gene polymorphisms with bone mineral density in young women with Graves' disease

• Authors: Wanda Horst-Sikorska , Magdalena Ignaszak-Szczepaniak , Michalina Marcinkowska , Marta Kaczmarek , Malgorzata Stajgis , Ryszard Slomski
• Languages of publication: EN

Abstracts

EN

Graves' (GD) hyperthyroidism induces accelerated bone turnover that leads to decreased bone mineral density (BMD). The role of the VDR gene in predisposition to primary osteoporosis has been recognized. Recent studies show associations between the VDR gene polymorphisms and susceptibility to autoimmune diseases. Here we analyzed if VDR gene polymorphisms: BsmI, ApaI, TaqI, and FokI may predispose women with Graves' hyperthyroidism to BMD reduction or to disease development. The subjects were 75 premenopausal female Polish patients with GD and 163 healthy women. The genotyping was performed by the use of the restriction fragment length polymorphism analysis (RFLP). We studied the association of the VDR polymorphisms and their haplotypes with patients' BMD and also SNPs and haplotypes association with Graves' disease. We found a strong linkage disequilibrium for the BsmI, ApaI, and TaqI polymorphims that formed three most frequent haplotypes in Graves' women: baT (47.9%), BAt (34.9%), and bAT (16.4%). We did not show statistically significant association of analyzed VDR polymorphisms or haplotypes with decreased bone mineral density in Graves' patients. However, the presence of F allele had a weak tendency to be associated with Graves' disease (with OR=1.93; 95% CI: 0.97-3.84; p=0.058). In conclusion: VDR gene polymorphisms do not predict the risk of decreased BMD in Polish women with Graves'. It may be speculated that the F allele carriers of the VDR-FokI polymorphism are predisposed to Graves' disease development.

Keywords

EN

Graves' disease; bone mineral density; VDR polymorphisms

• Publisher: Polish Biochemical Society
• Journal: Acta Biochimica Polonica
• Year: 2008
• Volume: 55
• Issue: 2
• Pages: 371-380

Dates

published

2008

received

2007-09-14

revised

2008-04-09

accepted

2008-04-23

(unknown)

2008-05-26

Contributors

author

Wanda Horst-Sikorska

• Department of Family Medicine, Poznan University of Medical Sciences, Poznań, Poland

author

Magdalena Ignaszak-Szczepaniak

• Department of Family Medicine, Poznan University of Medical Sciences, Poznań, Poland

author

Michalina Marcinkowska

• Department of Family Medicine, Poznan University of Medical Sciences, Poznań, Poland

author

Marta Kaczmarek

• Institute of Human Genetics, Polish Academy of Sciences, Poznań, Poland

author

Malgorzata Stajgis

• Endocrinology Outpatient Clinic of Juraszow Hospital, Poznań, Poland

author

Ryszard Slomski

• Department of Biochemistry and Biotechnology, Poznan University of Agriculture, Poznań, Poland

References

• Ban Y, Taniyama M, Ban Y (2000a) Vitamin D receptor gene polymorphism is associated with Graves' disease in the Japanese population. J Clin Endocrinol Metab 85: 4639-4643.
• Ban Y, Ban Y, Taniyama M, Katagiri T (2000b) Vitamin D receptor initiation codon polymorphism in Japanese patients with Graves' disease. Thyroid 10: 475-480.
• Braga V, Sangalli A, Malerba G (2002) Relationship among VDR (BsmI and FokI), COLIA1 and CTR polymorphisms with bone mass, bone turnover markers and sex hormones in men. Calcif Tissue Int 70: 457-462.
• Chen H, Chen W, Hsu C (2001) Relation of BsmI vitamin D receptor gene polymorphism to bone mineral density and occurrence of osteoporosis in postmenopausal Chinese women in Taiwan. Osteoporos Int 12: 1036-1041.
• Colin E, Uitterlinden A, Meurs J (2003) Interaction between vitamin D receptor genotype and estrogen receptor alpha genotype influences vertebral fracture risk. J Clin Endocrinol Metab 88: 3777-3784.
• Collins JE, Heward JM, Nithiyananthan S, Nithiyananthan R, Nejentsev S, Todd JA, Franklyn JA, Gough SC (2004) Lack of the vitamin D receptor gene with Graves' disease in UK Caucasians. Clin Endocrinol (Oxf) 60: 618-624.
• Deng H, Shen F, Xu F (2002) Tests of linkage and/or association of genes for vitamin D receptor, osteocalcin, and parathyroid hormone with bone mineral density. J Bone Miner Res 17: 678-686.
• Diamond T, Nery I, Hales I (1991) A therapeutic dilema: supressive doses of thyroxin significantly reduce bone mineral measurements in both premenopausal and postmenopausal women with thyroid cancer. J Clin Endocrinol Metab 72: 1184-1188
• Diamond T, Vine J, Smart R (1994) Thyrotoxic bone disease in women: a potentially reversible disorder. Ann Intern Med 120: 8-21.
• Donner H, Rau H, Walfish P (1997) CTLA-4 alanine-17 confers genetic susceptibility to Graves' disease and to type 1 diabetes mellitus. J Clin Endocrinol Metab 82: 143-146.
• Ferrari S, Rizolli R, Manen D (1998) Vitamin D receptor gene start codon polymorphisms (FokI) and bone mineral density: interaction with age, dietary calcium and 3'-end region polymorphisms. J Bone Miner Res 13: 925-930.
• Greenspan S, Greenspan F (1999) The effect of thyroid hormone on skeletal integrity. Ann Intern Med 130: 750-758.
• Hansen T, Abrahamsen B, Henriksen FL, Hermann AP, Jensen LB, Hørder M, Gram J (1998) Vitamin D receptor alleles do not predict bone mineral density or bone loss in Danish perimenopausal women. Bone 22: 571-575.
• Horst-Sikorska W, Wawrzyniak A, Celczyńska-Bajew L (2005) Polymorphism of VDR gene - the most effective molecular marker of osteoporotic bone fractures risk within postmenopausal women from Wielkopolska region of Poland. Endokrynol Pol 56: 233-239 (in Polish).
• Horst-Sikorska W (2005) Hyperthyroidism In Metabolic disorders of bone. Badurski J, Borgis, eds, pp 210-216, Warszawa (in Polish).
• Jodar E, Munoz-Torres M, Escobar-Jiminez F (1997) Bone loss in hyperthyroid patients and in former hyperthyroid controlled on medical therapy: influence of aetiology and menopause. Clin Endocrinol (Oxf) 47: 279-285.
• Langdahl B, Gravholt C, Brixen K (2000) Polymorphisms in the vitamin D receptor gene and bone mass, bone turnover and osteoporotic fractures. Eur J Clin Invest 30: 608-617.
• Kalak R, Horst-Sikorska W, Słomski R (2000) Genetic background of osteoporosis. Current state of research. Post Biol Komórki 27: 53-71 (in Polish).
• Kisakol G, Kaya A, Gonen S (2003) Bone and calcium metabolism in subclinical autoimmune hyper and hypothyroidism. Endocr J 50: 657-661.
• Kubota M, Yoshida S, Kieda M (2001) Association between two types of vitamin D receptor gene polymorphism and bone status in premenopausal Japanese women. Calcif Tissue Int 68: 16-22.
• Kuryłowicz A, Ramos-Lopez E, Badenhoop K (2005) Association of the vitamin D receptor (VDR) polymorphisms with Graves' disease in Polish population. Endokrynol Pol 4: 433 (in Polish).
• Morita A, Iki M, Dohi Y (2004) Prediction of bone mineral density from vitamin D receptor polymorphisms is uncertain in representative samples of Japanese women. The Japanese population-based osteoporosis (JPOS) study. Int J Epidemiol 33: 979-988.
• Morrison N, Qi J, Tokita A (1994) Prediction of bone density from vitamin D receptor alleles. Nature 367: 284-287.
• Morrison N, Qi J, Tokita A (1997) Prediction of bone density from vitamin D receptor alleles (correction). Nature 387: 106.
• Obermayer-Pietsch B, Fruhauf G, Chararas K (2000) Association of the vitamin D receptor genotype BB with low density in hyperthyroidism. J Bone Miner Res 15: 1950-1955.
• Ramoz-Lopez E, Kurylowicz A, Bednarczuk T, Paunkovic J, Seidl C, Badenhoop K (2005) Vitamin D receptor polymorphisms are associated with Graves' disease in German and Polish but no in Serbian patients. Thyroid 15: 1125-1130.
• Rubin L, Hawker G, Peltekova V (1999) Determinants of peak bone mass: clinical and genetic analyses in a young female Canadian cohort. J Bone Miner Res 14: 633-643.
• Skowrońska-Jóźwiak E, Adamczewski Z, Marcinkowska M (1999) The influence of suppressive dose of l-thyroxin on bone mineral density in premenopausal and postmenopausal women. Endokrynol Pol 50: 361-366 (in Polish).
• Walker-Bone K, Walter G, Cooper C (2002) Recent developments in the epidemiology of osteoporosis. Curr Opin Rheumatol 14: 411-415.