بررسی ارتباط پلی‌مورفیسم rs587777844 در ژن KISS1R با ناباروری در جمعیتی از زنان استان گیلان

نویسندگان
زکیه سیاهپوش
حمیدرضا وزیری
حسین روحی
دانشگاه گیلان
10.29252/jmj.15.1.16
چکیده
گیرنده­یKISSPEPTIN، به عنوان یک GPCR، انتقال دهنده­ی بسیاری از پیام­های خارج سلولی به داخل سلول است و بنابراین نقش کلیدی در تنظیم فعالیت و فیزیولوژی سلول دارد. ژن KISS1R در ناحیه­ی کروموزومی   19p13.3 قرار دارد. عدم عملکرد آن مسئول طیف وسیعی از بیماری­ها از جمله ناباروری و سرطان است. یکی از علت­های بالقوه مهم در ناباروری جهش­ در ژن KISS1R می­باشد. چون KISS1R در مسیر هیپوتالاموس- هیپوفیز- غددجنسی نقش مهمی دارد و منجر به تنظیم تولیدمثل و بلوغ در مهره­داران می­شود. هدف این مطالعه، بررسی ارتباط پلی­مورفیسمrs587777844  ژنKISS1R  که منجر به جایگزینی اسیدآمینه تیروزین   با   هیستیدین  در موقعیت 313 پروتئین گیرنده می­شود  با ناباروری در زنان استان گیلان بود. در این پژوهش نمونه خون از 40 زن نابارور (گروه بیمار) و 40 زن سالم (گروه کنترل) گرفته شد.  DNAژنومی از خون این افراد استخراج گردید. قطعات پلی­مورفیسمی مورد نظر تحت واکنش زنجیره­ای پلیمراز اختصاصی الل (AS-PCR) قرار گرفت. در نهایت آنالیز داده­ها با استفاده از نرم­افزار Medcalc (v 13.0)  انجام گرفت. نتایج به­دست آمده نشان می­دهد که ارتباط معنی داری در توزیع ژنوتیپی (03/0=P < /span>) و همچنین در توزیع آللی (0113/0=P < /span>) بین افراد بیمار و کنترل وجود دارد. به طور کلی، نتایج به دست آمده از این پژوهش پیشنهاد می­کند که در جمعیت مورد بررسی، احتمال همراهی  پلی­مورفیسم کدون 313 ژن KISS1R  به عنوان یک عامل خطر منجر با ناباروری در زنان نشان میدهد.
کلیدواژه‌ها
ناباروری
ژن KISS1R
پلی‌مورفیسم

عنوان مقاله English

Studying the association of rs587777844 KISS1R gene polymorphism with infertility in a woman population from Guilan province

نویسندگان English

Zakieh Siahpoosh
Hamidreza Vaziri
Hossein Roohi
چکیده English

The KISS1-derived peptide receptor (KISS1R), as a G protein-coupled receptor (GPCR), transduces a wide variety of extracellular signals into the cell and therefore has a key role in regulating cell function and physiology. KISS1R gene is located on chromosome 19p13.3 and its dysfunction is responsible for wide ranges of diseases including cancer and infertility. Infertility is an inability to conceive after at least one year of unprotected sexual intercourses. It is a multifactorial disorder which affected by male and female factors. Mutations in the KISS1R gene is one of the most important potential causes of infertility. KISS1R has an important role in regulating the Hypothalamic-Pituitary-Gonadal (HPG) axis that leads to regulate reproduction and maturation in vertebrates. The aim of this study was to evaluate the association of Tyr313His (rs587777844) polymorphism of KISS1R gene with female infertility in Guilan province. At first, the blood samples were obtained from 40 infertile women as cases and 40 healthy women as controls. Genomic DNA was extracted from peripheral blood leukocytes and allele specific PCR (AS-PCR) method was applied for determination of codon variation. Statistical analysis using Medcalc software (v 13.0) showed significant differences in genotype frequencies between healthy and patient groups (P-Value = 0.009). The distribution of allele frequencies between two groups also showed significant differences (P-Value = 0.0113). In conclusion, our study suggests that Tyr313His polymorphism of KISS1R gene may be considered as a risk factor for female infertility.

کلیدواژه‌ها English

infertility
KISS1R gene
Polymorphism
1. Warren BD, Kinsey WK, McGinnis LK, Christenson LK, Jasti S, Stevens AM, et al. Ovarian autoimmune disease: clinical concepts and animal models. Cellular & molecular immunology. 2014;11(6):510-21. 2. Zegers-Hochschild F, Adamson GD, de Mouzon J, Ishihara O, Mansour R, Nygren K, et al. The international committee for monitoring assisted reproductive technology (ICMART) and the world health organization (WHO) revised glossary on ART terminology, 2009. Human Reproduction. 2009:dep343. Hull M, Glazener C, 3. Kelly N, Conway D, Foster P, Hinton R, et al. Population study of causes, treatment, and outcome of infertility. Br Med J (Clin Res Ed). 1985;291(6510):1693-7. 4. Tinneberg H-R, Gasbarrini A. Infertility today: the management of female medical causes. International Journal of Gynecology & Obstetrics. 2013;123:S25-S30. 5. Luciano AA, Lanzone A, Goverde AJ. Management of female infertility from hormonal causes. International Journal of Gynecology & Obstetrics. 2013;123:S9-S17. Abrao MS, Muzii L, Marana 6. R. Anatomical causes of female infertility and their management. International Journal of Gynecology & Obstetrics. 2013;123:S18-S24. 7. Weiss RV, Clapauch R. Female infertility of endocrine origin. Arquivos Brasileiros de Endocrinologia & Metabologia. 2014;58(2):144-52. 8. Crujeiras AB, Casanueva FF. Obesity and the reproductive system disorders: epigenetics as a potential bridge. Human reproduction update. 2014:dmu060. 9. Hameed S, Jayasena CN, Dhillo WS. Kisspeptin and fertility. Journal of Endocrinology. 2011;208(2):97-105. 10. Seminara S, Crowley Jr W. Kisspeptin and GPR54: discovery of a novel pathway in reproduction. Journal of neuroendocrinology. 2008;20(6):727-31. 11. Skorupskaite K, George JT, Anderson RA. The kisspeptin-GnRH pathway in human reproductive health and disease. Human reproduction update. 2014;20(4):485-500. 12. Pinilla L, Aguilar E, Dieguez C, Millar RP, Tena-Sempere M. Kisspeptins and reproduction: physiological roles and regulatory mechanisms. Physiological reviews. 2012;92(3):1235-1316. 13. Kotani M, Detheux M, Vandenbogaerde A, Communi D, Vanderwinden J-M, Le Poul E, et al. The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54. Journal of Biological Chemistry. 2001;276(37):34631-6. 14. Cvetković D, Babwah AV, Bhattacharya M. Kisspeptin/KISS1R system in breast cancer. J Cancer. 2013;4(8):653. 15. Lee J-H, Miele ME, Hicks DJ, Phillips KK, Trent JM, Weissman BE, et al. KiSS-1, a novel human malignant melanoma metastasis-suppressor gene. Journal of the National Cancer Institute. 1996;88(23):1731-7. 16. Muir AI, Chamberlain L, Elshourbagy NA, Michalovich D, Moore DJ, Calamari A, et al. AXOR12, a novel human G protein-coupled receptor, activated by the peptide KiSS-1. Journal of Biological Chemistry. 2001;276(31):28969-75. 17. Reynolds RM, Logie JJ, Roseweir AK, McKnight AJ, Millar RP. A role for kisspeptins in pregnancy: facts and speculations. Reproduction. 2009;138(1):1-7. Roseweir A, Millar R. The role of 18. kisspeptin in the control of gonadotrophin secretion. Human reproduction update. 2009;15(2):203-12. Simpson JL. Genetic and Nongenetic Causes of Pregnancy Loss. Women. 2013;3(30):4.19 20. Greil AL, Slauson‐Blevins K, McQuillan J. The experience of infertility: a review of recent literature. Sociology of health & illness. 2010;32(1):140-62. 21. Brioude F, Bouligand J, Francou B, Fagart J, Roussel R, Viengchareun S, et al. Two families with normosmic congenital hypogonadotropic hypogonadism and biallelic mutations in KISS1R (KISS1 receptor): clinical evaluation and molecular characterization of a novel mutation. PLoS One. 2013;8(1): e53896. 22. Seminara SB, Messager S, Chatzidaki EE, Thresher RR, Acierno Jr JS, Shagoury JK, et al. The GPR54 gene as a regulator of puberty. New England Journal of Medicine. 2003;349(17):1614-27. 23. Semple R, Achermann J, Ellery J, Farooqi I, Karet F, Stanhope R, et al. Two novel missense mutations in g protein-coupled receptor 54 in a patient with hypogonadotropic hypogonadism. The Journal of Clinical Endocrinology & Metabolism. 2005;90(3):1849-55. 24. Pankov YA. Kisspeptin and leptin in the regulation of fertility. Molecular Biology. 2015;49(5):631-7. 25. Teles MG, Trarbach EB, Noel SD, Guerra-Junior G, Jorge A, Beneduzzi D, et al. A novel homozygous splice acceptor site mutation of KISS1R in two siblings with normosmic isolated hypogonadotropic hypogonadism. European Journal of Endocrinology. 2010;163(1):29-34. 26. Luan X, Zhou Y, Wang W, Yu H, Li P, Gan X, et al. Association study of the polymorphisms in the KISS1 gene with central precocious puberty in Chinese girls. European Journal of Endocrinology. 2007;157(1):113-8.