Association between Follicle Stimulating Hormone Receptor (FSHR) Polymorphism and Polycystic Ovary Syndrome among Egyptian Women.

Background: Polycystic ovary syndrome (PCOS) is an endocrine disorder and the criteria are specified by common complex genetic hyperandrogenism, oligomenorrhea or amenorrhea and polycystic ovary morphology. It is a leading cause of female infertility. The prevelance of PCOS among reproductive age women has been estimated to be 4-12%. The association between PCOS and FSH receptor (FSHR) polymorphism attracts wide attention. The aim of the present study was to evaluate whether polymorphism of FSHR at Ala307Thr codon is associated with PCOS and with clinical features of PCOS patients in Egypt. Results: PCOS patients (n=64) and control subjects (n=65) in the reproductive age were recruited from the outpatient clinic of Obstetrics and Gynecology Department, Mansoura University, Egypt. The Ala307Thr polymorphism in FSHR, and the frequency of respective genotypes was studied and statistical analysis was performed. We found that the heterozygote Ala/Thr genotype was associated with PCOS (64.1%, OR=2.68, CI=0.97, P= 0.033) compared with controls. Conclusion: The variant of Ala307Thr polymorphism of FSHR was associated with PCOS but it may be related to high total testosterone levels. In addition the FSHR polymorphism was not associated with either luteinizing hormone or follicular stimulating hormone. The present study suggests that the variant of the FSHR gene may act as a causative factor of PCOS in Egyptian women.

Association of polymorphisms G(–174)C in IL-6 gene and G(–1082)A in IL-10 gene with traditional cardiovascular risk factors in patients with coronary artery disease.

Interleukin-6 (IL-6) polymorphism has been associated with the genetic susceptibility to coronary artery disease (CAD) and also with the lipid profile in different populations. The present work aimed at studying the association, if any between the IL-6 (174) G/C and IL-10 (1082) G/A genes with hypertension or hyperlipidimia in Egyptian patients with CAD and the association of the IL-6 -174 G/C polymorphism with serum IL-6 levels. 108 Egyptian patients with CAD and 143 unrelated healthy subjects were included in the study. The different genotypes of IL-6 and IL-10 were detected by polymerase chain reaction. Serum levels of lipoprotein(a) [Lp(a)] and IL-6 were estimated in the patients, as well as in the healthy subjects. Increased frequency of G allele, GG and GC genotypes in IL-6, as well as decreased frequency of C allele and CC genotype were found in CAD patients, compared to healthy subjects [P = < 0.0001, OR = 3.95, 95% CI (2.16–7.22) for GG and GC vs CC genotype], [P = < 0.0001, OR = 3.44, 95% CI (2.26–5.23) for G allele]. There was an increased frequency of G allele vs A allele in IL-10 genotype in CAD patients, compared to healthy subjects [P = 0.005, OR = 1.866, 95% CI (1.2–2.9]. Higher levels of both Lp(a) and IL-6 were observed in CAD patients, compared to control subjects (P = 0.0012, P = 0.0346, respectively). Increased frequency of IL-6 -174 G-allele was implicated in a greater cardiovascular risk and the presence of G allele or homozygosity for G allele of IL-10 G/A (1082) was associated with an increased prevalence of CAD. The GC genotype and G allele in IL-6 had significant correlation with hyperlipidimic CAD patients; however, G allele in IL-6 and IL-10 showed significant association with hypertension. Thus, G allele in IL-6 and IL-10 was considered as an independent risk factor in hypertensive CAD patients.

Association of Angiotensin-I-Converting Enzyme (ACE) Insertion/Deletion Gene Polymorphism with End Stage Renal Disease in Egyptian Patients.

Angiotensin-I-converting enzyme (ACE) insertion/deletion (I/D) polymorphism has been associated with the genetic susceptibility to end stage renal disease (ESRD) in different populations. ACE DD genotype and D allele are associated with ESRD as risk factors in several studies. In this study, we investigated the association between ACE I/D gene polymorphism and ESRD in the Egyptian patients. Frequencies of D allele and DD genotype were significantly increased, while frequencies of I allele and ID genotype were significantly decreased in the ESRD patients when compared with the control subjects (P = .012, OR = 1.82, 95% CI = 1.139-2.915 for DD) and (P = .018, OR = 1.6, 95% CI = 1.082-2.33 for D). In conclusion, ACE DD genotype and D allele are associated with ESRD as risk factors for ESRD in the Egyptian population.

Role of Human Beta Defensin-2 and Oxidative Stress Parameters in Ovarian Cancer Patients.

To determine the role of human beta defensin-2 and oxidative stress by measuring serum human beta defensin-2 and antioxidant parameters in ovarian cancer patients. Study Design: Serum human beta defensin-2 (HBD-2), and the levels of antioxidants such as serum superoxide dismutase (SOD) and catalase (CAT), as well as blood reduced glutathione (GSH) and serum total antioxidant capacity (TAC) and serum malondialdhyde (MDA) were estimated in the circulation of 29 ovarian cancer patients and 15 of agematched normal subjects as control. Place and Duration of Study: Department of Gynecology, Mansoura University Hospital, between May 2011 and November 2012. Methodology: We included 29 patients (all women; age range 20-76 years) with ovarian cancer and the control group comprised 15 age-matched women free from diseases (age range 22-65 years)and was recruited from the gynecology outpatient clinic, Mansoura University. Exclusion criteria were lack of informed consent, patients with associated gynecologic malignancies like cervical, uterine, breast cancers, preexisting immunological as rheumatoid arthritis, psoriasis, Crohn's disease, smoking, and other associated malignancies as colonic, lung carcinoma. Also, patients with any concomitant illness such as obvious systemic infection, diabetes mellitus, hypertension, and renal diseases prior chemo- or radiotherapy, or using corticosteroid therapy were excluded. Results: A highly significant lowered levels of human beta defensin-2 (.85 +/- .26 ng/ml, P=0.001), catalase activities (504.98 +/- 107.65 U/L, P=0.001), reduced glutathione levels (7.24 +/- 5.36 mg/dl, P=0.001) and total antioxidant capacity levels (1.53 +/- .24 mmol/L, P=0.001) compared with controls (2.74 +/- .92 ng/ml, 717.57 +/- 67.32 U/L, 14.79 +/- 4.29 mg/dl and 2.10 +/- .27 mmol/L respectively). On the other hand, highly significant increased in the concentration of malondialdhyde (9.36 +/- 3.30 mmol/ml, P=0.001) and significantly increased of superoxide dismutase % inhibition (56.70 +/- 9.23 %inhibition, P=0.044) were observed in ovarian cancer patients as compared with controls (6.00 +/- 2.06 mmol/ml and 49.69 +/- 16.83 %inhibition respectively). Conclusion: The results would suggest that lower human beta defensin-2 as well as oxidative stress may be putative factors in the pathogenesis of ovarian cancer.

Glutathione S-Transferase Enzyme (GSTT1 and GSTM1) Gene Polymorphisms and Oxidative Stress in Egyptian Patients with End Stage Renal Disease.

Glutathione S-transferase enzyme (GSTT1 and GSTM1) gene polymorphisms have been associated with the genetic susceptibility to end stage renal disease (ESRD) in different populations. We investigated the association between GSTT1 and GSTM1 genes, and ESRD in Egyptian population. The samples of 133 ESRD and 91 control subjects were collected, and their clinical characteristics were assayed. Glutathione S-transferase enzyme (GSTT1 and GSTM1) gene polymorphisms were detected by polymerase chain reaction (PCR). Serum level of malondialdehyde (MDA), the oxidative stress and lipid peroxidation biomarker, and plasma glutathione S-transferase enzyme (GST), the antioxidant enzyme, were estimated in the ESRD patients as well as in the control subjects. We demonstrated the association of MDA and GST enzyme levels with GSTT1 and GSTM1 genotypes. We investigated the association between MDA and lipid parameters in the ESRD patients. Increased of the GSTM1 deletion genotype, (GSTT1/0) and both deletion genotypes (0/0) in the ESRD patients when compared with the control subjects (P < 0.0001, OR = 3.786, 95% CI = 2.151-6.664), (P = 0.001, OR = 3.172, 95% CI = 1.595-6.308) and (P = 0.045, OR = 1.945, 95% CI = 1.009-3.749), respectively. Highly significant increase of MDA level in the ESRD patients as compared with the control subjects (P < 0.0001). Highly significant decrease of GST enzyme level in the ESRD patients as compared with the control subjects (P < 0.0001).The level of MDA is significantly increased in all GST genotypes in the ESRD patients as compared with the control group. Also, there were significant association between The genetic risk factors of GSTT1 and GSTM1 genes in the ESRD, and high level of MDA in the ESRD patients, while the level of GST enzyme is significantly decreased in GST genotypes except the both deletion (0/0) genotypes, in which the level of GST enzyme is not significantly decreased in the ESRD patients as compared with the control subjects. There are significant association between the genetic risk factors of GSTT1 and GSTM1 genes in the ESRD, (GSTM1 null and GSTT1/0 genotypes), and low level of GST enzyme in the ESRD patients. There were significant positive correlation between MDA and total cholesterol, triglyceride, and LDL-cholesterol, and significant negative correlation between MDA and HDL-cholesterol in the ESRD patients as compared with the control subjects. In conclusion, the GSTM1 (null) genotype, (GSTT1/0) and (0/0) genotypes are independent risk factors for ESRD. The oxidative stress and lipid abnormalities are associated with ESRD in the studied Egyptian population.

Angiotensin-I-Converting Enzyme (ACE) Insertion/Deletion Polymorphism in Egyptian Patients with Coronary Artery Disease.

Angiotensin-I-converting enzyme (ACE) insertion/deletion (I/D) polymorphism has been associated with the genetic susceptibility to coronary artery disease (CAD) and also with the lipid profile in different populations. One hundred and eight Egyptian patients with CAD and one hundred forty three unrelated healthy subjects were included in the study. ACE I/D polymorphism was detected by polymerase chain reaction. We investigated the association between I/D polymorphism of the ACE gene and the presence of CAD as well as its association with hypertension in the patients. Serum levels of lipoprotein (a), Lp (a), and interleukin-6 (IL-6) were estimated in the patients as well as in the healthy subjects. Increased frequency of D allele and DD genotype as well as decreased frequency of I allele and ID genotype were found in CAD patients compared to healthy subjects (P = .004, OR= 0.419, 95% CI (.2 - .8), for DD genotype), (P = .008, OR= 0.475, 95% CI (0.27- 0.84), for D allele). Higher levels of both Lp (a) and IL-6 were observed in CAD patients compared to control subjects (P = .0012, P = .0346, respectively). No association was observed in ACE gene polymorphism with diabetes mellitus or hyperlipidemia. However, there is a trend for DD genotype to develop more hypertension than ID genotype (P=0.08, OR=2.88). In conclusion, theI/D polymorphism of the ACE gene (carrying the D allele) is an independent risk factor for CAD in the studied Egyptian population.