Polycystic Ovary Syndrome (PCOS) is a complex genetic disorder in reproductive-aged women which is associated with comorbidities of reproductive, metabolic, cardiovascular, endocrine, and psychological nature. PCOS is the most common cause of anovulatory infertility. Pathogenesis of PCOS involves strong interaction between environmental and genetic factors. Many Single-Nucleotide Polymorphisms (SNPs) have been associated with PCOS in different populations. Currently, very limited association studies of PCOS and infertility have been done on Pakistani population. The variants DENND1A rs9696009 and ERBB4 rs2178575 are significantly associated with PCOS in Chinese and European populations. These candidate genes regulate the production of androgen hormone, Anti-Mullerian Hormone (AMH), and luteinizing hormone. All these hormones are involved pathogenesis of PCOS and infertility. The aim of the study is to find an association of DENND1A rs9696009 and ERBB4 rs2178575 variants with PCOS in infertile Pakistani females. In this case-control study, 300 infertile females were recruited. The cases (n = 160) were infertile female diagnosed with PCOS (Rotterdam Criteria), and controls (n = 140) were infertile women with no evidence of PCOS. The genomic DNA was isolated, and genotyping was done by PCR-Restriction fragment length polymorphism and further validated by DNA Sanger Sequencing. The Chi-Square analysis showed 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). Furthermore, multinomial logistic regression analysis was performed and revealed that rs2178575 (ERBB4) heterozygous genotypes (GA) and mutant genotypes (AA) decrease 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 ERBB4 variant is significantly associated with PCOS infertile women and genetically indicated that ERBB4 (rs2178575) decreases the risk of infertility in females having PCOS.
BACKGROUND: Deficiency of silent information regulator 1 (SIRT1) can trigger inflammation, mitochondrial malfunctioning, and apoptosis through the hypothalamic-pituitary-ovarian axis, producing poor quality oocytes, leading to infertility. Normal vitamin D (VD) levels promote SIRT1 activity required for optimal fertility, and low levels of either may result in fertility problems owing to cell-membrane de-stabilization, increased autophagy, DNA damage leading to increased reactive oxygen species and mitochondrial dysfunction. Therefore, in this study, we want to estimate the levels of VD, SIRT1 and antioxidants (MnSOD; manganese superoxide dismutase, GR; glutathione reductase, visfatin) and oxidants (adrenaline & cortisol) in individuals living with infertility and explore the association of VD with SIRT1 expression (levels), antioxidants, and oxidants contributing to infertility in women. The significance of this study is that it highlights the importance of maintaining optimal levels of VD for reproductive health in females. METHODS: This cross-sectional study included 342 (135 infertile and 207 fertile) female subjects. Serum levels of MnSOD, SIRT1, visfatin, GR, VD, adrenaline, and cortisol were analyzed by ELISA and were compared in fertile and infertile samples using the Mann Whitney U test. RESULTS: There were significantly high levels of VD, SIRT1, GR, MnSOD and visfatin in fertile female participants. However, mean adrenaline and cortisol levels were higher in infertile samples with a significant negative correlation with VD. A significant negative correlation of VD with MnSOD, SIRT1, visfatin and GR was observed (p <0.01). In VD subset groups, MnSOD levels were significantly high in VD sufficient groups however, adrenaline and cortisol levels were significantly high in groups suffering from VD deficiency. CONCLUSIONS: Deficiency of VD is associated with a decrease in SIRT1 and other antioxidants, which may deter natural reproductive functions leading to infertility. Further studies are required to determine the cause-effect relationship of VD deficiency on conception and interpretation of the involved mechanism.
Infertility, Female , Vitamin D Deficiency , Humans , Female , Vitamin D , Antioxidants/metabolism , Sirtuin 1 , Nicotinamide Phosphoribosyltransferase , Hydrocortisone , Cross-Sectional Studies , Vitamins , Vitamin D Deficiency/metabolism , Oxidants
OBJECTIVE: The study was performed to investigate the association of hypertension in pregnancy with prostasin gene polymorphism in Pakistani females. METHODS: This case-control study was performed at University of Karachi, Pakistan from April 2018 to May 2019. A total of 160 females, including 90 hypertensives and 70 healthy pregnant females, were recruited by purposive sampling after obtaining informed written consent. Genotyping was performed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). RESULTS: The frequencies of the TC and CC genotypes were higher in hypertensive pregnant females compared to healthy controls. A significant difference was evident for CC (P=0.012) genotype; however, no significant difference was observed for TC (P=0.49) and TT genotypes (P=0.06) between control and hypertensive groups. The adjusted odds ratio for CC genotype was 6.2 (P=0.025) and 1.48 (P=0.44) for TC genotype compared to the TT genotype. There was a significantly higher prevalence of the C allele of the prostasin gene at rs12597511 in the hypertensive group, suggesting that this allele is a risk factor for hypertension and cardiovascular diseases. CONCLUSION: C allele at rs12597511 of prostasin gene demonstrate as a risk factor for having hypertension in pregnancy.
Coronavirus disease 2019 (COVID-19) is a contagious disease that has a potential of causing cardiovascular illness. Cardiac outcomes of COVID-19 mainly include acute coronary syndrome, heart failure, and left ventricular dysfunction. However, pericardial involvement is very rare. Here, we present a case of pericarditis and pericardial effusion in a known hypertensive COVID-19 patient. Our case was a diagnostic dilemma as the literature review mentioned that cardiovascular manifestations are mostly reported in symptomatic and critically ill patients of COVID-19. However, this patient has no viral respiratory illness, and is otherwise healthy.
Objectives To measure serum neopterin levels in blood donors of the local population and to study its relationship with age and blood group of transfusion-transmitted infection (TTI) negative blood donors. Methodology This cross-sectional study was carried out in the Department of Physiology at Liaquat National Hospital and Medical College (LNMC), Karachi, Pakistan, in collaboration with the Basic Medical Sciences Institute and Jinnah Post Graduate Medical Centre (JPMC). Data were collected from January 2018 to July 2018. A total of 174 blood donors participated in the study, who were selected by using a random sampling technique. They were screened through the standard procedures used for screening at the JPMC blood bank for TTIs as per the World Health Organization recommendations. Serum neopterin was estimated using enzyme-linked immunosorbent assay (ELISA) kits. Data analysis was performed using Statistical Package for Social Sciences (SPSS) version 23 (IBM Corp., Armonk, NY, USA). Chi-square and ANOVA (analysis of variance) were applied, and tests of significance were kept as P < 0.05. Results Neopterin level in the serum of TTI-positive blood donors was 15.1 ± 4.59 nmol/L, which was above the normal range and cutoff value of 10 nmol/L, whereas the neopterin level in the serum of TTI-negative blood donors was 6.1 ± 1.82 nmol/L (P = 0.001). In TTI-negative blood donors, the neopterin levels were within normal limits and were not influenced by age and blood groups (P > 0.05). Conclusions Serum neopterin levels did not report any significant difference in terms of age and blood group of TTI-negative blood donors and were seen to be within normal limits.
