Influence of KISS1 gene polymorphisms on the risk of polycystic ovary syndrome and its associated variables, in Saudi women.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex multifactorial disorder, affecting millions of women worldwide. The role of genetic polymorphisms of the KISS1 gene on the development of PCOS is still obscure. This study was designed to investigate the probable influence of KISS1 gene polymorphisms on PCOS and its associated variables: BMI, waist-hip ratio, kisspeptin, LH, FSH, and LH-FSH ratio. METHODS: The study comprised 104 PCOS women and 109 controls, with age ranging from 19 to 36 years. BMI, waist-hip ratio, and circulating levels of kisspeptin, LH, and FSH were measured. DNA was extracted, and genotyping of the KISS1 gene was carried out by nucleotide sequencing. The PCOS-associated variables were analyzed in different genotypes of single nucleotide polymorphisms (SNPs) of the KISS1 gene. RESULTS: The values of waist-hip ratio (WHR), LH, and LH-FSH ratio were significantly higher in PCOS women than controls. BMI, kisspeptin, and FSH levels exhibited no significant difference between the groups. Six novel SNPs of KISS1 gene were identified. Three: rs372790354G > A, rs12998G > A, and rs35431622A > T were investigated. Among these SNPs, the genotype and allele frequencies of rs372790354 showed significant association with PCOS (GA: p = 0.018, AA: p = 0.022, mutant allele-A: p = 0.021) and the G allele was protective. The values of LH, kisspeptin, and WHR of PCOS women were significantly influenced (p < 0.05) by the AA genotype of rs372790354. The other two SNPs rs12998G > A and rs35431622A > T revealed no significant influence on PCOS and associated variables. Haplotypes were constructed, but there was no significant difference between the patients and controls. CONCLUSION: In conclusion, this is the first study, which reports a significant influence of KISS1 gene polymorphism (rs372790354G > A) on PCOS and its associated variables. However, more extensive research is necessary to confirm these findings.

The influence of the rs1137101 genotypes of leptin receptor gene on the demographic and metabolic profile of normal Saudi females and those suffering from polycystic ovarian syndrome.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is of frequent occurrence in Saudi females and is often associated with obesity, insulin resistance, hypogonadotropic hypogonadism, and infertility. Since these features are also associated with leptin receptor (LEP-R) deficiency, several studies have attempted to link LEP-R gene polymorphisms to PCOS. METHODS: The purpose of this study is to assess the possible association of LEP-R gene polymorphism (rs1137101) with the main obesity-linked metabolic parameters in Saudi female patients affected by PCOS. A cohort of 122 Saudi female subjects, attending the outpatient's clinics at Makkah, Saudi Arabia and diagnosed with PCOS was investigated. Metabolic parameters in serum samples, including lipidogram, glucose, leptin, ghrelin and insulin and obesity markers (BMI, W/H ratio, HOMA) were assayed and compared with values from 130 healthy female volunteers (controls). The genotyping of rs1137101 polymorphism in the leptin receptor gene by amplification (PCR) followed by DNA sequencing, was conducted in both groups (PCOS and controls). RESULTS: Waist/hip ratio (W/H ratio), leptin serum levels and triglycerides appeared to be associated with PCOS but, aside from W/H ratio (AA s GG p = 0.009), this association also occurred for controls. No significant association in the leptin gene polymorphic locus rs1137101 with PCOS was seen in the results of the present study. In the control group, BMI, W/H ratio, leptin, Insulin, and HOMA-IR were significantly higher in the GG genotype compared to AA. CONCLUSION: Despite previous suggestion about a relationship between rs1137101, serum leptin levels, and PCOS, our studies do not show any statistical association and further investigations; possibly by also evaluating obese patients should be needed to elucidate this issue better.

rs4889 polymorphism in KISS1 gene, its effect on polycystic ovary syndrome development and anthropometric and hormonal parameters in Saudi women.

BACKGROUND: Kisspeptin is involved in female reproduction. This study was designed to i- estimate kisspeptin levels in women with polycystic ovary syndrome (PCOS), in comparison with controls, ii- study the correlations between kisspeptin and PCOS-related reproductive hormones, and iii- investigate the relation between KISS1 gene polymorphisms and hormone levels in women suffering from PCOS. METHODS: The investigation was a clinically designed study on 28 women with PCOS, and 30 normal, healthy women with no signs of PCOS as controls. Blood samples were collected between day 3 and day 6 of the menstrual cycle in both groups at 8:00 a.m., and circulating levels of LH, FSH and kisspeptin were estimated. DNA was extracted from whole blood and all coding exons of KISS1 gene were sequenced. RESULTS: Women with PCOS had higher LH levels and BMI compared to controls. Plasma kisspeptin levels were positively correlated with LH levels. There was no statistically significant difference between the groups in terms of kisspeptin and FSH levels. The SNP rs4889 C/G, a non-synonymous SNP, was investigated in the PCOS group. The frequency of GG genotype was significantly higher in the PCOS compared to the controls. These patients were more obese, had higher kisspeptin and FSH levels. CONCLUSION: The results of the study show that the genetic variation of KISS1 gene may be a factor contributing to PCOS development. The association between the gene and the gene variation and PCOS need further validation in large-scaled and functional studies.

Septicemia caused by Enterococcus coli in a pregnant woman after cerclage-A case report.

The objective of this case report is to discuss a case of septicemia caused by Escherichia coli following cervical cerclage. The study described a case of a 42-year-old female patient who visited the Ante-natal Clinic for a follow-up appointment during the 8th week of gestation. The patient had previously undergone successful in vitro fertilization treatment following 16 years of primary infertility. A routine ultrasound scan revealed cervical dilatation of 2-3 cm. The patient was advised to undergo cervical cerclage insertion. Two days after the surgery, she presented with pneumonia and also experienced vaginal bleeding, necessitating the removal of the cervical cerclage. Unfortunately, the patient suffered a stillbirth. Her condition deteriorated the following day, leading to septic shock and multiple organ dysfunction. After receiving the treatment, the patient was discharged; 2 days after being discharged the patient's blood culture and sensitivity results indicated a significant growth of Escherichia coli and a diagnosis of toxic myocarditis. Following 2 months of intensive treatment, the patient showed significant improvement; however, there was the presence of some mild renal impairment and he was ultimately discharged home. Maternal sepsis poses a significant risk to the health and lives of pregnant women. Escherichia coli stands out as a primary causative agent after cervical cerclage.

Global Transcriptional Profiling of Granulosa Cells from Polycystic Ovary Syndrome Patients: Comparative Analyses of Patients with or without History of Ovarian Hyperstimulation Syndrome Reveals Distinct Biomarkers and Pathways.

Ovarian hyperstimulation syndrome (OHSS) is often a complication of polycystic ovarian syndrome (PCOS), the most frequent disorder of the endocrine system, which affects women in their reproductive years. The etiology of OHSS is multifactorial, though the factors involved are not apparent. In an attempt to unveil the molecular basis of OHSS, we conducted transcriptome analysis of total RNA extracted from granulosa cells from PCOS patients with a history of OHSS (n = 6) and compared them to those with no history of OHSS (n = 18). We identified 59 significantly dysregulated genes (48 down-regulated, 11 up-regulated) in the PCOS with OHSS group compared to the PCOS without OHSS group (p-value < 0.01, fold change >1.5). Functional, pathway and network analyses revealed genes involved in cellular development, inflammatory and immune response, cellular growth and proliferation (including DCN, VIM, LIFR, GRN, IL33, INSR, KLF2, FOXO1, VEGF, RDX, PLCL1, PAPPA, and ZFP36), and significant alterations in the PPAR, IL6, IL10, JAK/STAT and NF-κB signaling pathways. Array findings were validated using quantitative RT-PCR. To the best of our knowledge, this is the largest cohort of Saudi PCOS cases (with or without OHSS) to date that was analyzed using a transcriptomic approach. Our data demonstrate alterations in various gene networks and pathways that may be involved in the pathophysiology of OHSS. Further studies are warranted to confirm the findings.

Adverse Effects of Selected Markers on the Metabolic and Endocrine Profiles of Obese Women With and Without PCOS.

The aim of the present study, is to investigate the influence of obesity, with and without polycystic ovarian syndrome (PCOS), on the levels of kisspeptin, vitamin D (Vit D), and vascular endothelial growth factor (VEGF) and to explore the relationship between these parameters and endocrine and metabolic variables. The study group included 126 obese Saudi females. Of these 63 were suffering from PCOS while the rest were normo-ovulatory obese women (non-PCOS obese). In the obese PCOS, VEGF was almost four times as high as in the non-PCOS obese, while kisspeptin and Vit D did not differ. A highly significant elevation was recorded in the waist/hip (WHR), cholesterol, LDL-C, fasting glucose, LH, LH/FSH ratio, estradiol (E2), and testosterone, while hip circumference, leptin, progesterone, and sex hormone binding globulin (SHBG) were lower in the obese PCOS subjects. BMI, HDL-C, ghrelin, insulin, and FSH levels did not differ significantly between the two groups. The obese PCOS had the same level of insulin resistance as the non-PCOS group, as judged by QUICK Index. Correlation studies showed a significant negative correlation between kisspeptin and glucose and LH levels, and a positive correlation with LH/FSH ratio in obese PCOS while in the non-PCOS obese, the kisspeptin correlated positively with glucose, and there was no correlation with LH or LH/FSH. VEGF negatively correlated with FSH and positively with LH/FSH ratio in the non-PCOS obese but this was lost in the obese PCOS. PCOS had no effect on the correlation between Vit D and all studied parameters. Multiple regression analysis showed triglyceride as predictor variable for kisspeptin as a dependent variable, while, leptin is a predictor variable for VEGF as a dependent variable. ROC studies showed the highest sensitivity and specificity for VEGF (AOC=1.00), followed by LH/FSH ratio (AOC=0.979). In conclusion, our study shows that PCOS results in significant elevation of VEGF in obese females, while kisspeptin and Vit D levels are not affected. It also leads to elevation in several of the lipid and hormonal abnormalities in the obese females. In addition, PCOS influences relationship between Kisspeptin and VEGF and some parameters such as glucose, LH or FSH and LH/FSH ratio in obese females, but does not affect Vit D relationship with other parameter.

The Gln27Glu polymorphism in ß2-adrenergic receptor gene is linked to hypertriglyceridemia, hyperinsulinemia and hyperleptinemia in Saudis.

BACKGROUND: ß2-adrenoceptor (ß2AR) gene polymorphism glutamine 27 glutamic acid (Gln27Glu) and Arg16Gly were reported to have an association with obesity and obesity related disorders in some population. We evaluated Gln27Glu polymorphism in the ß2AR gene in obese Saudi populations to investigate the association of ß2AR gene with obesity and other related metabolic parameters. DESIGN: We studied possible association of Gln27Glu in ß2AR gene with body mass index (BMI), anthropometric measurements and other metabolic parameters. The ß2AR gene polymorphism (Gln27Glu) was identified by sequencing PCR products representing locus of interest. Based on BMI, the subjects were divided into three groups, normal weight, overweight and obese. The genotype and allele frequency were calculated separately for each group. RESULTS: The allelic frequency of Glu27 did not differ amongst the three groups, though the Glu27 homozygote (Glu/Glu) were more in obese subjects and had higher concentration of triglyceride, leptin and insulin compared to in the Gln27 heterozygotes and Gln/Gln homozygotes. CONCLUSIONS: In this study we were able to provide evidence on the influence of Gln27Glu genetic variant of ß2AR gene on lipid phenotypes, insulin and leptin levels in the Saudi populations.

Polymorphic Variations in VDR Gene in Saudi Women with and Without Polycystic Ovary Syndrome (PCOS) and Significant Influence of Seven Polymorphic Sites on Anthropometric and Hormonal Parameters.

BACKGROUND: This study was designed to evaluate the associations between vitamin D receptor (VDR) gene polymorphisms and biochemical characteristics of Saudi women with polycystic ovary syndrome (PCOS). METHODS: Serum levels of LH, FSH, and Vitamin D were measured in 33 women: 16 patients and 17 normal controls (18 to 36 years). DNA was extracted and used for sequencing of the exons of VDR gene using ABI PRISM 3730xi Genetic Analyzer. RESULTS: Weight, BMI, Vit D, LH and FSH levels were higher in the PCOS patients compared to control group, where Vit D level correlated positively and significantly with FSH, in the control, but showed a negative and non-significant correlation in the PCOS patients. Sequencing results showed extensive polymorphisms in both groups, but the differences in the frequencies were not significant. Demographic and hormonal parameters were compared in the different genotypes of the SNPs. Significant differences were ob served in the values of the studied parameters in rs11168276, rs11168266, rs3858733, rs121909790, rs11168265 and rs731236. Vitamin D level was influenced significantly by the genotypes of rs11168265 (AA) (p=0.008), rs11168276 (AA; p=0.018) and rs731236 (CC; p=0.024). CONCLUSION: Vitamin D deficiency does not associate with PCOS in Saudi females. Several SNPs are identified in the VDR gene, in normal and PCOS females, but there is no difference in their frequencies between the two groups. The results show that polymorphism in VDR gene influences certain anthropometric and hormonal parameters in PCOS patients. Further detailed studies are required to confirm the associations between VDR and PCOS.

Arginine 16 Glycine Polymorphism in ß2-Adrenergic Receptor Gene is Associated with Obesity, Hyperlipidemia, Hyperleptinemia, and Insulin Resistance in Saudis.

Background. Several studies have shown an association between codon 16 polymorphism of the ß2AR gene and obesity. Methods. We studied the association between Arg16Gly polymorphism and obesity and its influence on anthropometric parameters, lipids, insulin resistance and leptin in Saudi individuals. The study group included 329 individuals (males: 109 and females: 220). Metabolic parameters, including glucose, lipids, insulin, and leptin were analyzed and anthropometric parameters including waist and hip circumference, waist/hip (W/H) ratio, and body mass index (BMI) were measured and HOMA-IR was calculated. Genotyping was conducted by DNA sequencing of 353 bp fragments, carrying the Arg16Gly polymorphic site. Results and Conclusion. Overweight and obese subjects had a significantly higher frequency of Gly16 (0.375 and 0.38, resp.) compared with normal-weight subjects (0.200). In addition, subjects carrying Gly16 allele regardless of their BMI had greater waist and hip circumference, W/H ratio, plasma lipids, leptin, glucose level, and insulin resistance as judged from the HOMA-IR, compared to those with the wild-type allele. The findings of this study show a significant association between the Arg16Gly polymorphism in ß2AR gene and the development of insulin resistance, overweight, and obesity in Saudi populations with an influence on the levels of lipid and leptin.

Circulating ghrelin levels and the polycystic ovary syndrome: correlation with the clinical, hormonal and metabolic features.

OBJECTIVES: Dysregulation of ghrelin levels may lead to physiological problems including obesity and polycystic ovary syndrome (PCOS). The aim of the study was to compare ghrelin levels in women with and without PCOS. STUDY DESIGN: Serum ghrelin levels (pre- and post-prandial) were compared between 30 Saudi women suffering from PCOS and 30 healthy controls. The relationship between circulating ghrelin levels and other hormones was investigated. Anthropometric measurements were made for all subjects. Biochemical and hormonal investigations included plasma glucose, insulin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), 17ß-estradiol (E2), progesterone, testosterone and sex hormone binding globulin (SHGB), and serum ghrelin levels. The data were statistically analyzed using independent T-test and ANOVA. Correlation studies were performed between ghrelin levels and other variables. RESULTS: No differences were observed in the levels of ghrelin during fasting and the postprandial period in the PCOS (p=0.487) and control groups (p=0.378). A significant inverse correlation was observed in ghrelin levels (fasting and postprandial) levels and BMI (PCOS: r=-0.529; p=0.009, controls: r=-0.670; p=0.005); PCOS: r=-0.421; p=0.007, controls: r=-0.491; p=0.004 respectively). No correlations between ghrelin levels and other parameters were observed. CONCLUSION: The findings of the study suggest that circulating plasma ghrelin levels were found to be normal and were inversely related to BMI in women with PCOS. No relationship between circulating ghrelin levels and the abnormal hormonal pattern of the PCOS were observed.

Seropositivity of Chlamydia trachomatis among saudi pregnant women in makkah.

OBJECTIVE: To determine the seroprevalence rates of immunoglobulin G (IgG) and immunoglobulin M (IgM) to Chlamydia trachomatis in Saudi pregnant women. SUBJECTS AND METHODS: Using enzyme-linked immunosorbent assay (ELISA), a total of 1600 serum samples were tested for antibodies to Chlamydia trachomatis known to cause a variety of clinical syndromes in women and newborn infants. RESULTS: Chlamydia trachomatis IgG antibodies were detected in 8.7% and IgM antibodies were found in 1.5% of different age groups. CONCLUSION: Pregnant Saudi women have low prevalence rate of Chlamydia trachomatis IgG antibodies and lower prevalence for Chlamydia trachomatis IgM.