Date of Award

12-2-2022

Degree Type

Thesis

Degree Name

MPhil in Biological and Biomedical Sciences

First Advisor

Dr Rehana Rehman

Second Advisor

Dr Ambrin Fatima

Third Advisor

Dr Haq Nawaz Khan

Department

Biological and Biomedical Sciences

Abstract

Polycystic Ovary Syndrome (PCOS) a multifactorial genetic disorder associated with adverse reproductive, endocrine, metabolic, cardiovascular, and psychological outcomes. Association of PCOS with infertility is well studied and is thought to be responsible for 40% of female infertility. There is limited genetic data available on PCOS associated with infertility in the Pakistani population. We have selected the statistically top hits; DENND1A and ERBB4 from the meta-analysis of PCOS genome[1]wide association study to check the association of rs9696009 (DENND1A) and rs2178575 (ERBB4) in the Pakistani population. The objective is to find an association of rs9696009 (DENND1A) and rs2178575 (ERBB4) with phenotypic presentation of the syndrome in infertile Pakistani females. This is a case-control study which included infertile women with PCOS as cases and infertile women with no evidence of PCOS as controls. The genotyping of the SNPs rs9696009 (DENND1A) and rs2178575 (ERBB4) was done by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) which is cost-effective genotyping technique. The results of the RFLP were further validated by gold standard DNA Sanger Sequencing. To evaluate the association of PCOS polymorphisms rs9696009 (DENND1A) and rs2178575 (ERBB4) with infertility, the Chi-square test was performed. The results revealed that rs2178575 (ERBB4) was significantly associated with infertility (χ2=10.282, p=0.005852) while rs9696009 (DENND1A) did not show any significant association (χ2=3.10, p=0.212036). Multinomial logistic regression analysis was carried out to confirm that either the SNPs rs9696009 (DENND1A) and rs2178575 (ERBB4) increases the risk of infertility in PCOS women or play a protective role. Results of regression analysis indicated that rs2178575 (ERBB4) heterozygous genotypes (GA) and mutant genotypes (AA) increases the risk of infertility by 0.541 times (OR=0.541, 95% CI=0.314-0.930, p=0.026) and 0.416 times (OR= 0.416, 95% CI=0.228-0.757, p=0.004) respectively, compared to wild type genotype (GG). The significant association of ERBB4 variant with infertile women with PCOS suggests that ERBB4 (rs2178575) increases the risk of infertility in females with PCOS.

First Page

1

Last Page

84

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