Volume 13, Issue 12 (12-2015)                   IJRM 2015, 13(12): 793-800 | Back to browse issues page

XML Persian Abstract Print

Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
Mahmoudi T, Majidzadeh K, Farahani H, Mirakhorli M, Dabiri R, Nobakht H et al . Association of vitamin D receptor gene variants with polycystic ovary syndrome: A case control study. IJRM 2015; 13 (12) :793-800
URL: http://ijrm.ir/article-1-610-en.html
Association of vitamin D receptor gene variants with polycystic ovary syndrome: A case control study
Touraj Mahmoudi * 1, Keivan Majidzadeh2 , Hamid Farahani3 , Mojgan Mirakhorli4 , Reza Dabiri5 , Hossein Nobakht5 , Asadollah Asadi6
1- Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran , mahmouditouraj@gmail.com
2- Cancer Genetics Department, Breast Cancer Research Center (BCRC), ACECR, Tehran, Iran
3- Department of Physiology, School of Medicine, Qom University of Medical Sciences, Qom, Iran
4- Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
5- Internal Medicine Department, Semnan University of Medical Sciences, Semnan, Iran
6- Department of Biology, Faculty of Science, University of Mohaghegh Ardabili, Ardabil, Iran
Abstract:   (3234 Views)
Background: Vitamin D and insulin play an important role in susceptibility to polycystic ovary syndrome (PCOS), and therefore vitamin D receptor (VDR), parathyroid hormone (PTH), and insulin receptor (INSR) gene variants might be involved in the pathogenesis of PCOS. Objective: The present study was designed to investigate the possible associations between polymorphisms in VDR, PTH, and INSR genes and the risk of PCOS. Materials and Methods: VDR, PTH, and INSR gene variants were genotyped in 35 women with PCOS and 35 controls using Polymerase chain reaction – Restriction fragment length polymorphism method. Furthermore, serum levels of glucose and insulin were measured in all participants. Results: No significant differences were observed for the VDR FokI, VDR Tru9I, VDR TaqI, PTH DraII, INSR NsiI, and INSR PmlI gene polymorphisms between the women with PCOS and controls. However, after adjustment for confounding factors, the VDR BsmI “Bb” genotype and the VDR ApaI "Aa" genotype were significantly under transmitted to the patients (p= 0.016; OR= 0.250; 95% CI= 0.081-0.769, and p= 0.017; OR= 0.260; 95% CI= 0.086-0.788, respectively). Furthermore, in the women with PCOS, insulin levels were lower in the participants with the INSR NsiI "NN" genotype compared with those with the "Nn + nn" genotypes (P= 0.045). Conclusion: The results showed an association between the VDR gene BsmI and ApaI polymorphisms and PCOS risk. These data also indicated that the INSR "NN" genotype was a marker of decreased insulin in women with PCOS. Our findings, however, do not lend support to the hypothesis that PTH gene DraII variant plays a role in susceptibility to PCOS.
Keywords: Insulin, Insulin receptor, Polycystic ovary syndrome, Vitamin D receptor
Full-Text [PDF 452 kb]   (779 Downloads)    
Type of Study: Original Article |
References
1. Azziz R, Woods KS, Reyna R, Key TJ, Knochenhauer ES, Yildiz BO. The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab 2004; 89: 2745-2749. [DOI:10.1210/jc.2003-032046]
2. Moran LJ, Misso ML, Wild RA, Norman RJ. Impaired glucose tolerance, type 2 diabetes and metabolic syndrome in polycystic ovary syndrome: A systematic review and meta-analysis. Hum Reprod Update 2010; 16: 347-363. [DOI:10.1093/humupd/dmq001]
3. Kurabayashi T, Yahata T, Quan J, Tanaka K. Association of polymorphisms in the beta2 and beta3 adrenoceptor gene with polycystic ovary syndrome. J Reprod Med 2006; 51: 389-393.
4. Cankaya S, Demir B, Aksakal SE, Dilbaz B, Demirtas C, Goktolga U. Insulin resistance and its relationship with high molecular weight adiponectin in adolescents with polycystic ovary syndrome and a maternal history of polycystic ovary syndrome. Fertil Steril 2014; 102: 826-830. [DOI:10.1016/j.fertnstert.2014.05.032]
5. Panidis D, Balaris C, Farmakiotis D, Rousso D, Kourtis A, Balaris V, et al. Serum parathyroid hormone concentrations are increased in women with polycystic ovary syndrome. Clin Chem 2005; 51: 1691-1697. [DOI:10.1373/clinchem.2005.052761]
6. Hahn S, Haselhorst U, Tan S, Quadbeck B, Schmidt M, Roesler S, et al. Low serum 25-hydroxyvitamin D concentrations are associated with insulin resistance and obesity in women with polycystic ovary syndrome. Exp Clin Endocr Diab 2006; 114: 577-583. [DOI:10.1055/s-2006-948308]
7. Mahmoudi T, Gourabi H, Ashrafi M, Yazdi RS, Ezabadi Z. Calciotropic hormones, insulin resistance and the polycystic vary syndrome. Fertil Steril 2010; 93: 1208-1214. [DOI:10.1016/j.fertnstert.2008.11.031]
8. Grundberg E, Brandstrom H, Ribom EL, Ljunggren O, Mallmin H, Kindmark A. Genetic variation in the human vitamin D receptor is associated with muscle strength, fat mass and body weight in Swedish women. Eur J Endocrinol 2004; 150: 323-328. [DOI:10.1530/eje.0.1500323]
9. Wehr E, Trummer O, Giuliani A, Gruber H, Pieber TR, Obermayer-Pietsch B. Vitamin D-associated polymorphisms are related to insulin resistance and vitamin D deficiency in polycystic ovary syndrome. Eur J Endocrinol 2011; 164: 741-749. [DOI:10.1530/EJE-11-0134]
10. Ranjzad F, Mahban A, Irani Shemirani A, Mahmoudi T, Vahedi M, Nikzamir A, et al. Influence of gene variants related to calcium homeostasis on biochemical parameters of women with polycystic ovary syndrome. J Assist Reprod Genet 2011; 28: 225-232. [DOI:10.1007/s10815-010-9506-4]
11. Zofkova II, Zajickova K, Hill M. Serum parathyroid hormone levels are associated with FokI polymorphism of the vitamin D receptor gene in untreated postmenopausal women. Eur J Intern Med 2003; 14: 232-236. [DOI:10.1016/S0953-6205(03)00065-7]
12. Lin MW, Tsai SJ, Chou PY, Huang MF, Sun HS, Wu MH. Vitamin D receptor 1a promotor -1521 G/C and -1012 A/G polymorphisms in polycystic ovary syndrome. Taiwan J Obstet Gynecol 2012; 51: 565-571. [DOI:10.1016/j.tjog.2012.09.011]
13. Mahmoudi T. Genetic variation in the vitamin D receptor and polycystic ovary syndrome risk. Fertil Steril 2009; 92: 1381-1383. [DOI:10.1016/j.fertnstert.2009.05.002]
14. Gohda T, Shou I, Fukui M, Funabiki K, Horikoshi S, Shirato I, et al. Parathyroid hormonr gene polymorphism and secondary hyperparathyroidism in hemodialysis patients. Am J Kidney Dis 2002; 39: 1255-1260. [DOI:10.1053/ajkd.2002.33399]
15. Goodarzi MO, Louwers YV, Taylor KD, Jones MR, Cui J, Kwon S, et al. Replication of association of a novel insulin receptor gene polymorphism with polycystic ovary syndrome. Fertil Steril 2011; 95: 1736-1741. [DOI:10.1016/j.fertnstert.2011.01.015]
16. Lee EJ, Yoo KJ, Kim SJ, Lee SH, Chan KY, Baek KH. Single nucleotide polymorphism in exon 17 of the insulin receptor gene is not associated with polycystic ovary syndrome in a Korean population. Fertil Steril 2006; 86: 380-384. [DOI:10.1016/j.fertnstert.2005.12.073]
17. Ranjzad F, Mahmoudi T, Irani Shemirani A, Mahban A, Vahedi M, Ashrafi M, et al. A common variant in the adiponectin gene and polycystic ovary syndrome risk. Mol Biol Rep 2012; 39: 2313-2319. [DOI:10.1007/s11033-011-0981-1]
18. Ferriman D, Gallwey JD: Clinical assessment of body hair growth in women. J Clin Endocrinol Metab 1961; 21: 1440–1447. [DOI:10.1210/jcem-21-11-1440]
19. Zawadski JK, Dunaif A. Diagnostic criteria for polycystic ovary syndrome: towards a rational approach. In: Dunaif A, Givens JR, Haseltine FP, Meriiam GR, Ed., Polycystic ovary syndrome. In: Hershman SM, Series Ed., Current Issues in Endocrinology and Metabolism. Blackwell, Boston, MA, USA, 1992; 377-384.
20. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412-419. [DOI:10.1007/BF00280883]
21. Flores-Martínez SE, Islas-Andrade S, Machorro-Lazo MV. DNA polymorphism analysis of candidate genes for type 2 diabetes mellitus in a Mexican ethnic group. Ann Genet 2004; 47: 339-348. [DOI:10.1016/j.anngen.2004.05.004]
22. Urbanek M, Legro RS, Driscoll D, Strauss JF, Dunaif A, Spielman RS. Searching for the polycystic ovary syndrome genes. J Pediatr Endocrinol Metab 2000; 13: 1311-1313.
23. Mukherjee S, Shaikh N, Khavale S, Shinde G, Meherji P, Shah N, et al. Genetic variation in exon 17 of INSR is associated with insulin resistance and hyperandrogenemia among lean Indian women with polycystic ovary syndrome. Eur J Endocrinol 2009; 160: 855-862. [DOI:10.1530/EJE-08-0932]
24. Oh JY, Barrett-Connor E. Association between vitamin D receptor polymorphism and type 2 diabetes or metabolic syndrome in community-dwelling older adults: the Rancho Bernardo study. Metabolism 2002; 51: 356-359. [DOI:10.1053/meta.2002.29969]
25. Fang Y, van Meurs JB, Alesio A, Jhamai M, Zhao H, Rivadeneira F, et al. Promoter and 3'-untranslated-region haplotypes in the vitamin d receptor gene predispose to osteoporotic fracture: the rotterdam study. Am J Hum Genet 2005; 77: 807-823. [DOI:10.1086/497438]
26. Whitfield GK, Remus LS, Jurutka PW, Zitzer H, Oza AK, Hope T, et al. Are human vitamin D receptor gene polymorphisms functionally significant? In: Norman AW, Bouillon R, Thomasset M. Vitamin D Endocrine System: structural, Biological Genetic and Clinical Aspects. California, USA: University of California, Riverside; 2000; 817- 824.
27. Apparao KB, Lovely LP, Gui Y, Lininger RA, Lessey BA. Elevated endometrial androgen receptor expression in women with polycystic ovarian syndrome. Biol Reprod 2002; 66: 297-304. [DOI:10.1095/biolreprod66.2.297]
28. Maestro B, Campion J, Davila N, Calle C. Stimulation by 1, 25-dihydroxyvitamin D3 of insulin receptor expression and insulin responsiveness for glucose transport in U-937 human promonocytic cells. Endocr J 2000; 47: 383-391. [DOI:10.1507/endocrj.47.383]
29. Darwish H, DeLuca HF. Vitamin D-regulated gene expression. Crit Rev Eukaryot Gene Expr 1993; 3: 89-116.
Send email to the article author

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Designed & Developed by : Yektaweb