Association Study of HSD11B1 rs12086634 (T>G) Gene Polymorphism with Polycystic Ovarian Syndrome in Erbil Province.
Background: Polycystic ovarian syndrome (PCOS) is one of the most prevalent gynaecological imbalances of endocrine hormones and metabolic disorders that affect women during puberty, with a prevalence of up to 17.8%.
Objective: The current study focused on the presence of rs12086634 T>G genetic variant of 11β-hydroxysteroid dehydrogenase type 1 (HSD11B1) gene polymorphism in Erbil province PCOS women.
Participants and methods: The present study was conducted on 104 PCOS women and 94 control women to investigate the association HSD11B1 rs12086634 (T>G) gene polymorphism with PCOS. The extracted genomic DNA from whole blood according to the protocol provided by the manufacturer company. HSD11B1 rs12086634 T>G gene polymorphism was detected by tetra primer-amplification refractory mutation system based polymerase chain reaction (T-ARMS-PCR) method.
Result: The obtained results suggest that the frequency of the HSD11B1 TG and GG genotypes in women with PCOS increased 3.60-fold and 4.39-fold compared to the control group (odds ratio [OR]; 3.60 and 4.39, 95% confidence interval [CI], 1.951-6.668 and 0.175-110.2; P-value <0.0001 and 0.22) respectively, the body mass index of women with G-allele was significantly greater than women with T-Allele (28.32 kg/ mt2 vs. 26.20 kg/ mt2,and p = 0.0256).
Conclusions: Our findings indicated and proved that the findings indicate that both homozygous and heterozygous genotypes of HSD11B1 rs12086634 T>G gene polymorphism was associated with PCOS in Erbil province.
ALFAISAL, A. H. M., AL NAJAR, A. F. & AL-DERESAWI, M. S. 2014. Detection of five substitution TPO mutations in Polycystic Ovary Syndrome (PCOS) and thyroid hormones disturbance patients. Jornal of Biotechnology Research Center, 8, 5-10.
ALI, R. J. 2016. Genetic Polymorphism in MTHFR and PCO genes associated with the incidence of Polycystic Ovary Syndrome in A sample of Iraqi Women. Master degree Msc, Al-Nahrain University.
AZZIZ, R., CARMINA, E., CHEN, Z., DUNAIF, A., LAVEN, J. S., LEGRO, R. S., LIZNEVA, D., NATTERSON-HOROWTIZ, B., TEEDE, H. J. & YILDIZ, B. O. 2016. Polycystic ovary syndrome. Nat Rev Dis Primers, 2, 16057.
BAPTISTE, C. G., BATTISTA, M.-C., TROTTIER, A. & BAILLARGEON, J.-P. 2010. Insulin and hyperandrogenism in women with polycystic ovary syndrome. The Journal of Steroid Biochemistry and Molecular Biology, 122, 42-52.
CHUA, A. K., AZZIZ, R. & GOODARZI, M. O. 2012. Association study of CYP17 and HSD11B1 in polycystic ovary syndrome utilizing comprehensive gene coverage. MHR: Basic science of reproductive medicine, 18, 320-324.
COOPER, M. S. & STEWART, P. M. 2009. 11β-Hydroxysteroid Dehydrogenase Type 1 and Its Role in the Hypothalamus-Pituitary-Adrenal Axis, Metabolic Syndrome, and Inflammation. The Journal of Clinical Endocrinology & Metabolism, 94, 4645-4654.
DEVANG, N., M, N., RAO, S. & ADHIKARI, P. 2016. HSD11B1 gene polymorphisms in type 2 diabetes and metabolic syndrome—Do we have evidence for the association? International Journal of Diabetes in Developing Countries, 36, 95-102.
DEVANG, N., SATYAMOORTHY, K., RAI, P. S., NANDINI, M., BASU, A. & ADHIKARI, P. 2018. Association of HSD11B1 rs12086634 and HSD11B1 rs846910 gene polymorphisms with polycystic ovary syndrome in South Indian women. International Journal of Diabetes in Developing Countries, 38, 381-386.
DEVANG, N., SATYAMOORTHY, K., RAI, P. S., NANDINI, M., RAO, S., PHANI, N. M. & ADHIKARI, P. 2017. Association of HSD11B1 gene polymorphisms with type 2 diabetes and metabolic syndrome in South Indian population. Diabetes research clinical practice, 131, 142-148.
DRAPER, N., POWELL, B. L., FRANKS, S., CONWAY, G. S., STEWART, P. M. & MCCARTHY, M. I. 2006. Variants implicated in cortisone reductase deficiency do not contribute to susceptibility to common forms of polycystic ovary syndrome. Clinical Endocrinology, 65, 64-70.
DRAPER, N., WALKER, E. A., BUJALSKA, I. J., TOMLINSON, J. W., CHALDER, S. M., ARLT, W., LAVERY, G. G., BEDENDO, O., RAY, D. W. & LAING, I. 2003. Mutations in the genes encoding 11β-hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate dehydrogenase interact to cause cortisone reductase deficiency. Nature genetics, 34, 434.
DUJIC, T., BEGO, T., MLINAR, B., SEMIZ, S., MALENICA, M., PRNJAVORAC, B., OSTANEK, B., MARC, J. & CAUSEVIC, A. 2012. Association between 11β-hydroxysteroid dehydrogenase type 1 gene polymorphisms and metabolic syndrome. Biochemia Medica, 22, 76-85.
ESHRE, T. R. & GROUP, A.-S. P. C. W. 2004. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertility and Sterility, 81, 19-25.
GAMBINERI, A., VICENNATI, V., GENGHINI, S., TOMASSONI, F., PAGOTTO, U., PASQUALI, R. & WALKER, B. R. 2006. Genetic variation in 11β-hydroxysteroid dehydrogenase type 1 predicts adrenal hyperandrogenism among lean women with polycystic ovary syndrome. The Journal of Clinical Endocrinology Metabolism, 91, 2295-2302.
HASHEMI, M., MOAZENI-ROODI, A., BAHARI, A. & TAHERI, M. 2012. A tetra-primer amplification refractory mutation system–polymerase chain reaction for the detection of rs8099917 IL28B genotype. Nucleosides, Nucleotides, Nucleic Acids, 31, 55-60.
HUGHES, K. A., WEBSTER, S. P. & WALKER, B. R. 2008. 11-Beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitors in type 2 diabetes mellitus and obesity. Expert opinion on investigational drug, 17, 481-496.
JAIN, S., PANDEY, P., JAIN, M. & SINGH, K. 2015. A Genetic Polymorphism of CYP1A1 (T6235C) Gene as a Risk Factor for Polycystic Ovary Syndrome. Andrology, 4, 2167-0250.10001.
JAKUBOWSKI, L. 2005. Genetic aspects of plycystic ovary syndrome. Endokrynologia Polska, 56, 285-291.
JOSEPH, S. & DAVID, W. R. J. T. Q. R. O. B. 2001. Molecular cloning: a laboratory manual. 76, 348-349.
KANNISTO, K., PIETILÄINEN, K. H., EHRENBORG, E., RISSANEN, A., KAPRIO, J., HAMSTEN, A., YKI-JÄRVINEN, H. J. T. J. O. C. E. & METABOLISM. 2004. Overexpression of 11β-hydroxysteroid dehydrogenase-1 in adipose tissue is associated with acquired obesity and features of insulin resistance: studies in young adult monozygotic twins. The Journal of Clinical Endocrinology Metabolism, 89, 4414-4421.
KHOSHNAW, A. A. O. 2018. SNPs Analysis in the CDKN2A/CDKN2B Genes in human assayed by DNA sequencing and ARMS™ test. ZANCO Journal of Pure Applied Sciences, 30, 57-66.
LEGRO, R. S., ARSLANIAN, S. A., EHRMANN, D. A., HOEGER, K. M., MURAD, M. H., PASQUALI, R. & WELT, C. K. 2013. Diagnosis and treatment of polycystic ovary syndrome: an Endocrine Society clinical practice guideline. The Journal of Clinical Endocrinology & Metabolism, 98, 4565-4592.
LIU, Y., MLADINOV, D., PIETRUSZ, J. L., USA, K. & LIANG, M. 2008. Glucocorticoid response elements and 11β-hydroxysteroid dehydrogenases in the regulation of endothelial nitric oxide synthase expression. Cardiovascular research, 81, 140-147.
MASUZAKI, H., PATERSON, J., SHINYAMA, H., MORTON, N. M., MULLINS, J. J., SECKL, J. R. & FLIER, J. S. 2001. A transgenic model of visceral obesity and the metabolic syndrome. Science, 294, 2166-2170.
MOHAMMED, M. B., AL-AWADI, S. J. & OMRAN, M. A. 2015. Association between polycystic ovary syndrome and genetic polymorphisms of CYP 17 gene in Iraqi women. Iraqi Journal of Biotechnology, 14, 99-110.
MOHAMMED, S. & AMEEN, E. 2017. Effect of Polycystic Ovarian Syndrome and Obesity on Women Fertility in Erbil Governorate. ZANCO Journal of Pure and Applied Sciences, 29, 56-65.
NADER, M. I. M. M. I. & AZIZ, I. H. 2014. Molecular Study of Insulin Resistance and Polycystic Ovary Syndrome. Iraqi Journal of Biotechnology, 13, 273-283.
NAIR, S., LEE, Y., LINDSAY, R., WALKER, B., TATARANNI, P., BOGARDUS, C., BAIER, L. & PERMANA, P. 2004. 11β-Hydroxysteroid dehydrogenase Type 1: genetic polymorphisms are associated with Type 2 diabetes in Pima Indians independently of obesity and expression in adipocyte and muscle. Diabetologia, 47, 1088-1095.
RAMADHAN, R. S. 2018. Molecular analysis of FSH receptor gene in Iraqi women with PCOS syndrome. Middle East Fertility Society Journal, 23, 404-408.
RODIN, A., THAKKAR, H., TAYLOR, N. & CLAYTON, R. 1994. Hyperandrogenism in Polycystic Ovary Syndrome--Evidence of Dysregulation of 11β-Hydroxysteroid Dehydrogenase. New England Journal of Medicine, 330, 460-465.
SAN MILLÁN, J. L., BOTELLA-CARRETERO, J. I., ÁLVAREZ-BLASCO, F., LUQUE-RAMÍREZ, M., SANCHO, J., MOGHETTI, P. & ESCOBAR-MORREALE, H. C. F. 2005. A study of the hexose-6-phosphate dehydrogenase gene R453Q and 11β-hydroxysteroid dehydrogenase type 1 gene 83557insA polymorphisms in the polycystic ovary syndrome. The Journal of Clinical Endocrinology Metabolism, 90, 4157-4162.
SHIMODAIRA, M., NAKAYAMA, T., SATO, I., SATO, N., IZAWA, N., MIZUTANI, Y., FURUYA, K. & YAMAMOTO, T. 2013. Glucocorticoid synthesis-related genes: HSD11B1 and HSD11B2 in hypertensive disorders in pregnancy. Gynecological Endocrinology, 29, 657-661.
TEEDE, H., DEEKS, A. & MORAN, L. 2010. Polycystic ovary syndrome: a complex condition with psychological, reproductive and metabolic manifestations that impacts on health across the lifespan. BMC medicine, 8, 41.
TOMLINSON, J. W., WALKER, E. A., BUJALSKA, I. J., DRAPER, N., LAVERY, G. G., COOPER, M. S., HEWISON, M. & STEWART, P. M. 2004. 11β-hydroxysteroid dehydrogenase type 1: a tissue-specific regulator of glucocorticoid response. Endocrine reviews, 25, 831-866.
WELT, C. K. & DURAN, J. M. 2014. Genetics of polycystic ovary syndrome. Semin Reprod Med, 32, 177-82.
WHITE, P. C. 2005. Genotypes at 11β-hydroxysteroid dehydrogenase type 11B1 and hexose-6-phosphate dehydrogenase loci are not risk factors for apparent cortisone reductase deficiency in a large population-based sample. 90, 5880-5883.
Copyright (c) 2019 Abdullah Abubaker Shareef, Mustafa Saber Al-Attar
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
At Zanco Journal, we're dedicated to protecting your rights as an author, and ensuring that any and all legal information and copyright regulations are addressed. Whether an author is published with Zanco Journal or any other publisher, we hold ourselves and our colleagues to the highest standards of ethics, responsibility and legal obligation