Molecular studies of CAPN-10 gene (rs2975760) and its association with Insulin Resistance in Polycystic Ovarian Syndrome of Iraqi women


  • Hadbaa H. Al-Murshedi Department of Chemistry and Biochemistry, College of Medicine, University of Kerbala, Kerbala, Iraq.
  • Ammar Fadhil Jawad Department of Pharmacognosy, College Pharmacy, University of Kerbala, Kerbala, Iraq.
  • Fadhil J. Al-Tu’ma Department of Chemistry and Biochemistry, College of Medicine, University of Kerbala, Kerbala, Iraq.
  • Eman A. Hadi Department of Chemistry, College of Science, University of Mosul, Mosul, Iraq.
  • Maha Mohammed Kadhim Al-Tu’ma Department of Anesthesia Techniques, College of Health and Medical Techniques, Al-Zahraa University for Women, Kerbala, Iraq.



Polycystic Ovary Syndrome, Insulin Resistance, CAPN10 gene


Objectives: To explore an association between CAPN10, SNP-44 (rs2975760) with IR condition in women with PCOS.

Methods: A study included 120 participants of which 68 women have PCOS subdivide according to their body mass index (BMI) into 45 obese (BMI≥30) and 23 non-obese (BMI<30). The remaining 52 represent the control group who were apparently healthy women with normal weight and normal menstrual cycle. Patients with PCOS were selected from the Infertility Department, Gynecology and Obstetrics Teaching Hospital, Kerbala Health Directorate / Kerbala-Iraq between Nov., 2021 and June, 2022. Diagnosis of PCOS is based on 2 of 3 findings: oligo/anovulation, hyperandrogenism, polycystic ovaries in ultrasound (Rotterdam criteria). Patients were interviewed and examined for weight, height, waist circumference, and hip circumference. Venous blood samples were collected at 9 AM after an overnight fast. IR was assessed by calculating homeostatic model assessment of insulin resistance (HOMA-IR) using the formula (fasting glucose mg/dl x fasting insulin µU/ml)/405, taking normal value <2.7. Genotypes of CAPN10, SNP-44 has been identified using Allele-specific polymerase chain reaction (AS-PCR) technique.

Results: The prevalence of IR based on HOMA-IR was (80%) in obese PCOS and (48%) in non-obese PCOS women. CAPN10, SNP-44 has been reconstructed and analyzed in patients and controls. Genotypes of 45 obese PCOS subjects (TT, N=26; TC, N=12; and CC, N=7), 23 non-obese PCOS subjects (TT, N=15; TC, N=6; and CC, N=2) and control subjects (TT, N=39; TC, N=11; and CC, N=2) were identified. The genotype distribution was statistically different between obese PCOS women and controls (OR=5.25, P=0.048). The association of SNP-44 allele with IR status was detected. HOMA-IR was greater in CC (10.54 ± 1.29, 9.88 ± 1.41) than in TT (3.30 ± 1.52, P<0.001; 2.82 ± 1.45, P<0.001) and TC (3.76 ± 1.58, P<0.001; 4.10 ±1.57, P<0.05) in obese PCOS and non-obese PCOS subjects respectively.

Conclusion: In obese PCOS, the C allele was associated with higher insulin secretion and HOMA-IR compared with the T allele. The increased HOMA-IR is an indicator of IR. In this scenario, the C allele might be involved in the pathophysiology of insulin resistance in PCOS.


Amato, M. C., Vesco, R., Vigneri, E., Ciresi, A. and Giordano, C. 2015. Hyperinsulinism and Polycystic Ovary Syndrome (PCOS): Role of Insulin Clearance. J Endocrinol Invest, 38, 1319-26.

Amisi, C. A. 2022. Markers of Insulin Resistance in Polycystic Ovary Syndrome Women: An Update. World Journal of Diabetes, 13, 129.

Azziz, R., Woods, K. S., Reyna, R., Key, T. J., Knochenhauer, E. S. And Yildiz, B. O. 2004. The Prevalence and Features of The Polycystic Ovary Syndrome In An Unselected Population. The Journal of Clinical Endocrinology and Metabolism, 89, 2745-2749.

Barber, T. M. and Franks, S. 2021. Obesity and Polycystic Ovary Syndrome. Clinical Endocrinology, 95, 531-541.

Broekmans, F., Knauff, E., Valkenburg, O., Laven, J., Eijkemans, M. and Fauser, B. 2006. PCOS According to The Rotterdam Consensus Criteria: Change in Prevalence Among WHO‐II Anovulation and Association with Metabolic Factors. Bjog: An International Journal of Obstetrics and Gynaecology, 113, 1210-1217.

Castelo-Branco, C., Steinvarcel, F., Osorio, A., Ros, C. and Balasch, J. 2010. Atherogenic Metabolic Profile in Pcos Patients: Role of Obesity and Hyperandrogenism. Gynecological Endocrinology, 26, 736-742.

Crisosto, N., De Guevara, A. L., Echiburú, B., Maliqueo, M., Cavada, G., Codner, E., Paez, F. and Sir-Petermann, T. 2019. Higher Luteinizing Hormone Levels Associated with Antimüllerian Hormone In Postmenarchal Daughters of Women with Polycystic Ovary Syndrome. Fertility and Sterility, 111, 381-388.

Dahan, M., Abbasi, F. and Reaven, G. 2007. Prevalence of Insulin Resistance among American Women with Polycystic Ovary Syndrome (PCOS) as a Function of Body Mass Index (BMI). Fertility and Sterility, 88, S78-S79.

Fauser, B. C., Tarlatzis, B. C., Rebar, R. W., Legro, R. S., Balen, A. H., Lobo, R., Carmina, E., Chang, J., Yildiz, B. O. and Laven, J. S. 2012. Consensus on Women’s Health Aspects of Polycystic Ovary Syndrome (PCOS): The Amsterdam Eshre/Asrm-Sponsored 3rd PCOS Consensus Workshop Group. Fertility and Sterility, 97, 28-38. E25.

Franks, S., Gharani, N., Waterworth, D., Batty, S., White, D., Williamson, R. and Mccarthy, M. 1997. The Genetic Basis of Polycystic Ovary Syndrome. Human Reproduction (Oxford, England), 12, 2641-2648.

Franks, S., White, D., Gilling-Smith, C., Carey, A., Waterworth, D. and Williamson, R. 1996. Hypersecretion Of Androgens By Polycystic Ovaries: The Role of Genetic Factors in The Regulation of Cytochrome P450c17α. Bailliere's Clinical Endocrinology and Metabolism, 10, 193-203.

Gonzalez, A., Abril, E., Roca, A., Aragón, M. J., Figueroa, M. J., Velarde, P., Ruiz, R. O., Fayez, O., Galán, J. J. and Herreros, J. A. 2003. Specific Capn10 Gene Haplotypes Influence The Clinical Profile of Polycystic Ovary Patients. The Journal of Clinical Endocrinology and Metabolism, 88, 5529-5536.

Haddad, L., Evans, J. C., Gharani, N., Robertson, C., Rush, K., Wiltshire, S., Frayling, T. M., Wilkin, T. J., Demaine, A. and Millward, A. 2002. Variation within The Type 2 Diabetes Susceptibility Gene Calpain-10 and Polycystic Ovary Syndrome. The Journal of Clinical Endocrinology and Metabolism, 87, 2606-2610.

Haddad, L., Gharani, N., Evans, J., Cela, E. and Franks, S. M M Linkage And Association of Variants of The Diabetes Susceptibility-Gene Niddm1 CAPN10 with Polycystic Ovarian Syndrome in European Parent-Offspring Trios. 82nd Annual Meeting of The Endocrine Society, Toronto, Ontario, Canada, 2000. 75.

Hestiantoro, A., Karimah, P. D., Shadrina, A., Wiweko, B., Muharam, R. and Astuti, B. P. K. 2019. Triglycerides, Independent of Ferriman Gallwey Score, Is A Main Determinant of Free Testosterone Index in PCOS. F1000research, 8.

Horikawa, Y., Oda, N., Cox, N. J., Li, X., Orho-Melander, M., Hara, M., Hinokio, Y., Lindner, T. H., Mashima, H. and Schwarz, P. E. 2000. Genetic Variation In The Gene Encoding Calpain-10 Is Associated With Type 2 Diabetes Mellitus. Nature Genetics, 26, 163-175.

Itriyeva, K. 2022. The Effects Of Obesity On The Menstrual Cycle. Current Problems In Pediatric And Adolescent Health Care, 101241.

Jensen, D. P., Urhammer, S. A., Eiberg, H., Borch-Johnsen, K., Jørgensen, T., Hansen, T. and Pedersen, O. 2006. Variation In Capn10 In Relation To Type 2 Diabetes, Obesity And Quantitative Metabolic Traits: Studies In 6018 Whites. Molecular Genetics And Metabolism, 89, 360-367.

Jones, M. R. and Goodarzi, M. O. 2016. Genetic Determinants Of Polycystic Ovary Syndrome: Progress And Future Directions. Fertility And Sterility, 106, 25-32.

Legro, R. S., Arslanian, S. A., Ehrmann, D. A., Hoeger, K. M., Murad, M. H., Pasquali, R. and Welt, C. K. 2013. Diagnosis And Treatment Of Polycystic Ovary Syndrome: An Endocrine Society Clinical Practice Guideline. The Journal Of Clinical Endocrinology and Metabolism, 98, 4565-4592.

Legro, R. S., Azziz, R., Ehrmann, D., Fereshetian, A. G., O’keefe, M., Ghazzi, M. N. and Group, P. T. S. 2003. Minimal Response Of Circulating Lipids In Women With Polycystic Ovary Syndrome To Improvement In Insulin Sensitivity With Troglitazone. The Journal Of Clinical Endocrinology and Metabolism, 88, 5137-5144.

Liu, Q., Xie, Y.-J., Qu, L.-H., Zhang, M.-X. and Mo, Z.-C. 2019. Dyslipidemia Involvement In The Development Of Polycystic Ovary Syndrome. Taiwanese Journal Of Obstetrics And Gynecology, 58, 447-453.

Lyssenko, V., Almgren, P., Anevski, D., Orho-Melander, M., Sjögren, M., Saloranta, C., Tuomi, T., Groop, L. and Group, B. S. 2005. Genetic Prediction Of Future Type 2 Diabetes. Plos Medicine, 2, E345.

March, W. A., Moore, V. M., Willson, K. J., Phillips, D. I., Norman, R. J. and Davies, M. J. 2010. The Prevalence Of Polycystic Ovary Syndrome In A Community Sample Assessed Under Contrasting Diagnostic Criteria. Human Reproduction, 25, 544-551.

Mayer, S. B., Evans, W. S. and Nestler, J. E. 2015. Polycystic Ovary Syndrome And Insulin: Our Understanding In The Past, Present And Future. Women’s Health, 11, 137-149.

Neumeyer, S., Hemani, G. and Zeggini, E. 2020. Strengthening Causal Inference For Complex Disease Using Molecular Quantitative Trait Loci. Trends In Molecular Medicine, 26, 232-241.

Rizzo, M., Berneis, K., Hersberger, M., Pepe, I., Di Fede, G., Rini, G. B., Spinas, G. A. and Carmina, E. 2009. Milder Forms Of Atherogenic Dyslipidemia In Ovulatory Versus Anovulatory Polycystic Ovary Syndrome Phenotype. Human Reproduction, 24, 2286-2292.

Shorakae, S., Ranasinha, S., Abell, S., Lambert, G., Lambert, E., De Courten, B. and Teede, H. 2018. Inter‐Related Effects Of Insulin Resistance, Hyperandrogenism, Sympathetic Dysfunction And Chronic Inflammation In Pcos. Clinical Endocrinology, 89, 628-633.

Simoni, M., Tempfer, C., Destenaves, B. and Fauser, B. 2008. Functional Genetic Polymorphisms And Female Reproductive Disorders: Part I: Polycystic Ovary Syndrome And Ovarian Response. Human Reproduction Update, 14, 459-484.

Spritzer, P. M. 2014. Polycystic Ovary Syndrome: Reviewing Diagnosis And Management Of Metabolic Disturbances. Arq Bras Endocrinol Metabol, 58, 182-7.

Unluer, A., Findik, R., Sevinc, N. and Karakaya, J. 2013. Comparison Of Hba1c Levels In Obese And Non-Obese Polycystic Ovarian Patients. Clinical And Experimental Obstetrics and Gynecology, 40, 148-150.




How to Cite

Al-Murshedi, H. H. ., Fadhil Jawad, A. ., Al-Tu’ma, F. J. ., Hadi, E. A. ., & Al-Tu’ma, M. M. K. . (2022). Molecular studies of CAPN-10 gene (rs2975760) and its association with Insulin Resistance in Polycystic Ovarian Syndrome of Iraqi women. Journal of Contemporary Medical Sciences, 8(6), 382–387.