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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.
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Kisspeptinas/genética , Síndrome do Ovário Policístico/genética , Adulto , Índice de Massa Corporal , Feminino , Hormônio Foliculoestimulante/metabolismo , Genótipo , Humanos , Kisspeptinas/metabolismo , Hormônio Luteinizante/metabolismo , Fenótipo , Síndrome do Ovário Policístico/metabolismo , Polimorfismo de Nucleotídeo Único , Arábia Saudita , Relação Cintura-Quadril , Adulto JovemRESUMO
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.
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Síndrome Metabólica/genética , Obesidade/genética , Síndrome do Ovário Policístico/genética , Polimorfismo de Nucleotídeo Único/genética , Receptores para Leptina/genética , Adulto , Índice de Massa Corporal , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Leptina/genética , Leptina/metabolismo , Arábia SauditaRESUMO
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.
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Índice de Massa Corporal , Hormônio Foliculoestimulante/sangue , Kisspeptinas/genética , Hormônio Luteinizante/sangue , Síndrome do Ovário Policístico/genética , Polimorfismo Genético , Adulto , Feminino , Humanos , Obesidade/complicações , Obesidade/epidemiologia , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/epidemiologia , Arábia Saudita/epidemiologia , Adulto JovemRESUMO
Genetic polymorphism in proinflammatory cytokine genes may be associated with the etiology of preterm birth (PTB). The current study was designed with the aim to explore the association of genetic polymorphisms and mRNA expression of IL-1α, IL-1ß, and TNF-α gene with preterm birth in the Saudi population. Genotyping of genomic DNA of 50 PTB patients and an equal number of controls were carried out using TaqMan Genotyping assay kits. Gene expression of each gene was carried out using quantitative RT-PCR. The cytokine levels in the serum of PTB patients and controls were measured by ELISA. A statistically significant association was observed between the rs361525 alleles (G and A) of TNF-α and PTB, where the mutant A allele was significantly protective against PTB development (OR= 0.362; χ2=4.31; p=0.038). The gene expression of all studied genes (IL1α, IL-1ß, IL-6, and TNF-α) was higher in the PTB patients, but the results reached significance only for IL-1ß (p=0.035). Elevated gene expression was also evident from the level of these proteins in plasma, where the level of IL1α, IL-ß were significantly higher in the serum of PTB patients compared to the controls, however, IL6 and TNF-α were significantly lower despite higher gene expression. For IL6, the lower level could be due to tocolytic treatment that was given to all women suffering from PTB. Receiver operating curves (ROC) were drawn for the studied cytokines. In conclusion, this study revealed that rs361525 polymorphism plays a role as a protective marker for PTB and the levels of IL-1α, IL-6, TNF- α can be used as predicative biomarkers for PTB I Saudi women.
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Interleucina-1alfa/genética , Interleucina-1beta/genética , Interleucina-6/genética , Polimorfismo de Nucleotídeo Único , Nascimento Prematuro/genética , Fator de Necrose Tumoral alfa/genética , Adulto , Feminino , Frequência do Gene , Humanos , Recém-Nascido , Interleucina-1alfa/sangue , Interleucina-1beta/sangue , Interleucina-6/sangue , Gravidez , Nascimento Prematuro/sangue , Nascimento Prematuro/epidemiologia , Arábia Saudita/epidemiologia , Transcriptoma , Fator de Necrose Tumoral alfa/sangueRESUMO
BACKGROUND: Polycystic ovary syndrome (PCOS) is considered as one of the most frequently encountered hormonal pathologies in women during their reproductive years. Leptin and ghrelin, peptide hormones with adipostatic and orexigenic effect, respectively, seem to be involved in the metabolic changes that occur in PCOS. The aim of this study was to determine serum ghrelin and leptin levels in obese and lean Saudi women with PCOS and to investigate their relationship to the metabolic profiles in these women. METHODS: This study was conducted as a prospective, observational, cross-sectional, case-control study, at the Department of Obstetrics and Gynecology, Al-Noor Hospital, Makkah, Kingdom of Saudi Arabia. The study population included 252 women [130 women with PCOS (diagnosed according to the Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus, 2003) and 122 normo-ovulatory women as matched controls] attending the outpatient Gynecology Clinic. Demographic details were recorded, blood was extracted following overnight fast and serum was used for the determination of serum ghrelin and leptin levels and other hormonal and biochemical parameters including total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, glucose, and insulin. Insulin resistance and sensitivity were calculated as HOMA-IR and HOMA-S. RESULTS: No significant differences in ghrelin (P = 0.1830) and leptin (P = 0.8329) levels were detected between the PCOS and control groups. However, ghrelin levels were significantly lower; and leptin levels were significantly higher in obese PCOS patients in comparison with lean patients (P = 0.0001 for both). In the PCOS group, there were significant correlations between ghrelin and leptin levels with Body Mass Index (BMI), waist-hip ratio, total cholesterol, triglycerides, HDL, LDL and insulin levels. Multiple regression analysis demonstrated that insulin was the main determinant for ghrelin (R2 = 0.316) and leptin (R2 = 0.352) levels (P = 0.0001 for both). CONCLUSIONS: Although serum ghrelin and leptin levels were found to be normal in women with PCOS; yet, there is a relationship, possibly linked to obesity, hyperinsulinemia and insulin resistance between these levels and metabolic profile of Saudi PCOS.
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Grelina/sangue , Leptina/sangue , Metabolômica , Obesidade/sangue , Síndrome do Ovário Policístico/sangue , Magreza/sangue , Adulto , Estudos de Casos e Controles , Feminino , Homeostase , Humanos , Resistência à Insulina , Arábia SauditaRESUMO
BACKGROUND: In some populations, obesity and body weight related disorders show a correlation with polymorphisms in three subtypes of beta-adrenoceptor (ß1, ß2, and ß3) [ADRB1, ADRB2 and ADRB3] genes. We scanned for the polymorphism of Arg389Gly (rs1801253) in ADRB1 and Trp64Arg (rs4994) in ADRB3 genes in Saudi population to determine association, if any, of these polymorphisms with obesity and related disorders. METHODS: We studied 329 non-related adults (33.1% men and 66.9% women), aged 18-36 years. Anthropometric measurements were recorded, and Body mass index (BMI) and waist/hip ratio were calculated; leptin, insulin, lipidogram, and glucose concentrations were determined. ADRB1 and ADRB3 polymorphisms (Arg389Gly and Trp64Arg, respectively) were screened by DNA sequencing. The subjects were divided into three groups according to BMI: normal weight (BMI < 25 kg/m2), overweight (BMI ≥25.1-29.9 kg/m2) subjects, and obese (≥30 kg/m2). RESULTS: In the age-matched groups of the normal weight, overweight and obese male and female subjects, all anthropometric parameters were found to be significantly higher, and in the obese group, all biochemical parameters were significantly elevated compared to the normal weight controls. The allelic frequency of Gly389 ADRB1 did not differ amongst the three groups, whereas the frequency of Arg64 of ADRB3 gene was significantly higher in the overweight and obese subjects, compared with the normal weight subjects. In addition, subjects carrying Arg64 allele regardless of their BMI had a greater waist and hip circumference, W/H ratio, plasma cholesterol, triglyceride, LDL, leptin, insulin, and glucose level compared to those with the wild-type Trp allele. CONCLUSION: The results of this study have shown a significant association between the Trp64Arg polymorphism in ADRB3 gene and the development of overweight and obesity in Saudi populations. It also has an influence on the levels of lipid, insulin, leptin, and glucose, whereas, Arg389Gly polymorphism in ADRB1 is not associated with overweight, obesity or dyslipidaemias in Saudis.
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Dislipidemias/genética , Polimorfismo Genético/genética , Receptores Adrenérgicos beta 3/genética , Adolescente , Adulto , Peso Corporal/genética , Peso Corporal/fisiologia , Feminino , Genótipo , Humanos , Masculino , Receptores Adrenérgicos beta 1/genética , Adulto JovemRESUMO
The mRNAs of most inflammatory mediators are short-lived due to AU-rich elements (AREs) in their 3'-untranslated regions. AREs ensure a low basal level of expression during homeostasis and a transient nature of expression during the inflammatory response. Here, we report that the mRNA of the pro-inflammatory chemokine IL-8, which contains an archetypal ARE, is unexpectedly constitutively abundant and highly stable in primary human monocytes and macrophages. Using the pre-monocyte-like THP-1 cell line that can differentiate into macrophage-like cells, we show that a low level of unstable IL-8 mRNA in undifferentiated cells (half-life<30 min) becomes constitutively elevated and the mRNA is dramatically stabilized in differentiated THP-1 cells with a half-life of more than 15 h similar to primary monocytes and macrophages. In contrast, the level and stability of TNF-α mRNA also containing an ARE is only slightly affected by differentiation; it remains low and unstable in primary macrophages and differentiated THP-1 cells with an estimated half-life of less than 20 min. This differentiation-dependent stabilization of IL-8 mRNA is p38 MAPK-independent and is probably coupled with reduced protein translation. Reporter assays in THP-1 cells suggest that the ARE alone is not sufficient for the constitutive stabilization in macrophage-like cells and imply an effect of the natural biogenesis of the transcript on the stabilization of the mature form. We present a novel, cell type-dependent sustained stabilization of an ARE-containing mRNA with similarities to situations found in disease.
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Interleucina-8/genética , Interleucina-8/metabolismo , Macrófagos/metabolismo , Monócitos/metabolismo , RNA Mensageiro/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Elementos Ricos em Adenilato e Uridilato/fisiologia , Diferenciação Celular , Linhagem Celular Tumoral , Dactinomicina/farmacologia , Células HeLa , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Inibidores da Síntese de Ácido Nucleico/farmacologia , Ésteres de Forbol/farmacologia , Estabilidade de RNA , Fator de Necrose Tumoral alfa/genéticaRESUMO
OBJECTIVES: To determine the allelic frequencies and effects of genotypic variations in cytokine gene polymorphisms in a Saudi Arabian population. METHODS: This cross-sectional study involved 41 patients with Primary Sjögren's syndrome (pSS) and 71 healthy controls between October 2018 and May 2019. Single nucleotide polymorphisms genotyping was performed using the SEQUENOM MassARRAY® System, targeting nine polymorphisms in different cytokine genes. Chi-square tests were used to compare the patients and controls. RESULTS: The interleukin-1 beta (IL-1ß) rs1143627 CT (control, 52.7%; patients, 21.2%) and TT + CT (p= 0.003; p=0.033) genotypes were less frequent in patients with pSS than in healthy controls. The C allele in rs10488631 in the interferon regulatory factor 5 (IRF5) gene and the A allele in rs12583006 in the B-cell activating factor (BAFF) gene were associated with an increased risk of pSS development in the patient group. CONCLUSION: The CT genotype at -31 (rs1143627) in the IL-1ß gene was not associated with a high risk of pSS development in the Saudi population, in contrast to what has been verified in other ethnicities. However, the C allele in rs10488631 in IRF-5 and the A allele in rs12583006 in BAFF were associated.
Assuntos
Polimorfismo de Nucleotídeo Único , Síndrome de Sjogren , Humanos , Estudos Transversais , Arábia Saudita , Síndrome de Sjogren/genética , Citocinas/genéticaRESUMO
Rheumatoid arthritis (RA) is a complex, multifactorial disorder with an autoimmune etiology. RA is highly heritable and is associated with both human leucocyte antigen (HLA) and non-HLA genes. We investigated the associations of 33 single nucleotide polymorphisms (SNPs) with RA in the Saudi population. METHODS: This study included 105 patients with RA and an equal number of age- and sex-matched controls. The patients with RA attended outpatient clinics at King Khalid University Hospital in Riyadh, Saudi Arabia. Blood samples were collected, and DNA was extracted using Qiagen kits. Primers were designed for the 33 selected SNPs using the MassEXTEND primers program, and samples were genotyped on the Sequenom MassARRAY iPLEX platform. The allele frequencies and genotypes were determined for each SNP, and the results obtained for the patients were compared to those for the controls. RESULTS: The allele and genotype frequencies of six SNPs were significantly associated with RA: rs1188934, rs10919563, rs3087243, rs1980422, rs10499194, and rs629326. The minor alleles of rs1188934, rs10919563, rs10499194, and rs629326 were protective, with odds ratios of 0.542, 0.597, 0.589, and 0.625, and p-values of 0.002, 0.023, 0.013 and 0.036, respectively. In addition, the heterozygote frequencies of two SNPs (rs6859219 and rs11586238) were significantly higher in the controls than in the patients. CONCLUSIONS: There is considerable heterogeneity in the genetics of RA in different populations, and the SNPs that are associated with RA in some populations are not in others. We studied 33 SNPs and only eight were associated with RA. The remaining SNPs showed no allelic or genotypic associations with RA.
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Rheumatoid arthritis (RA) is an autoimmune inflammatory disease that causes multi-articular synovitis. The illness is characterized by worsening inflammatory synovitis, which causes joint swelling and pain. Synovitis erodes articular cartilage and marginal bone, resulting in joint deterioration. This bone injury is expected to be permanent. Cytokines play a prominent role in the etiology of RA and could be useful as early diagnostic biomarkers. This research was carried out at Riyadh's King Khalid University Hospital (KKUH). Patients were enrolled from the Rheumatology unit. Seventy-eight RA patients were recruited (67 (85.9%) females and 11 (14.1%) males). Patients were selected for participation by convenience sampling. Demographic data were collected, and disease activity measurements at 28 joints were recorded using the disease activity score (DAS-28). Age- and sex-matched controls from the general population were included in the study. A panel of 27 cytokines, chemokines, and growth factors was determined in patient and control sera. Binary logistic regression (BLR) and discriminant analysis (DA) were used to analyze the data. We show that multiple cytokine biomarker profiles successfully distinguished RA patients from healthy controls. IL-17, IL-4, and RANTES were among the most predictive variables and were the only biomarkers incorporated into both BLR and DA predictive models for pooled participants (men and women). In the women-only models, the significant cytokines incorporated in the model were IL-4, IL-17, MIP-1b, and RANTES for the BLR model and IL-4, IL-1Ra, GM-CSF, IL-17, and eotaxin for the DA model. The BLR and DA men-only models contained one cytokine each, eotaxin for BLR and platelet-derived growth factor-bb (PDGF-BB) for DA. We show that BLR has a higher fidelity in identifying RA patients than DA. We also found that the use of gender-specific models marginally improves detection fidelity, indicating a possible benefit in clinical diagnosis. More research is needed to determine whether this conclusion will hold true in various and larger patient populations.
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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.
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Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme deficiency disorder affecting over 400 million individuals worldwide. G6PD protects red blood cells (RBC) from the harmful effects of oxidative substances. There are more than 400 G6PD mutations, of which 186 variants have shown to be linked to G6PD deficiency by decreasing the activity or stability of the enzyme. Different variants manifest different clinical phenotypes which complicate comprehending the mechanism of the disease. In order to carry out computational approaches to elucidate the structural changes of different G6PD variants that are common to the Asian population, a complete G6PD monomer-ligand complex was constructed using AutoDock 4.2, and the molecular dynamics simulation package GROMACS 4.6.7 was used to study the protein dynamics. The G410D and V291M variants were chosen to represent classes I and II respectively and were created by in silico site-directed mutagenesis. Results from the Root mean square deviation (RMSD), Root mean square fluctuation (RMSF) and Radius of gyration (Rg) analyses provided insights on the structure - function relationship for the variants. G410D indicated impaired dimerization and structural NADP binding while the impaired catalytic activity for V291M was indicated by a conformational change at its mutation site.
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The sickle cell (HbS) gene occurs at a variable frequency in the Middle Eastern Arab countries, with characteristic distribution patterns and representing an overall picture of blood genetic disorders in the region. The origin of the gene has been debated, but studies using ß-globin gene haplotypes have ascertained that there were multiple origins for HbS. In some regions the HbS gene is common and exhibits polymorphism, while the reverse is true in others. A common causative factor for the high prevalence and maintenance of HbS and thalassaemia genes is malaria endemicity. The HbS gene also co-exists with other haemoglobin variants and thalassaemia genes and the resulting clinical state is referred to as sickle cell disease (SCD). In the Middle Eastern Arab countries, the clinical picture of SCD expresses two distinct forms, the benign and the severe forms, which are related to two distinct ß-globin gene haplotypes. These are referred to as the Saudi-Indian and the Benin haplotypes, respectively. In a majority of the Middle Eastern Arab countries the HbS is linked to the Saudi-Indian haplotype, while in others it is linked to the Benin haplotype. This review outlines the frequency, distribution, clinical feature, management and prevention as well as gene interactions of the HbS genes with other haemoglobin disorders in the Middle Eastern Arab countries.
Assuntos
Anemia Falciforme/genética , Doenças Endêmicas , Haplótipos/genética , Hemoglobina Falciforme/genética , Globinas beta/genética , Anemia Falciforme/epidemiologia , Humanos , Malária/epidemiologia , Malária/genética , Oriente Médio/epidemiologia , Talassemia/genéticaRESUMO
BACKGROUND: Polycystic ovarian syndrome (PCOS) is a frequently encountered disorder. This study aimed to identify polymorphisms in ADRB2 in Saudi PCOS development and to study its influence on lipids, hormones, and anthropometric parameters. METHODS: Saudi females (100) suffering from PCOS and healthy controls (100) were investigated. The estimation of cholesterol, triglycerides, high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C), plasma glucose, leptin Insulin, and ghrelin were carried out. The DNA was extracted, and ADRB2 fragment carrying the exon 1 was amplified and sequenced. RESULTS: The waist, W/H ratio, lipids, glucose, and insulin were significantly higher in the obese PCOS compared to the normal weight group. The leptin and ghrelin were not different. Two single nucleotide polymorphisms (SNPs): rs1042713 (Arg16Gly; A>G) and rs1042714 (Gln27Glu; C>G) were identified. The genotype and allele frequency of rs1042713 did not differ in the total PCOS and normal weight, and obese PCOS compare to the controls. However, rs1042714 was significantly associated with PCOS development, where the minor G allele was protective against PCOS development. CONCLUSIONS: The rs1042714 polymorphism of the ADRB associates with PCOS development in Saudis, while rs1042713 does not. However, the GG genotype of rs1042713 associates significantly with elevated BMI, waist, hip, W/H, and leptin, and decreased ghrelin. On the other hand, rs1042714 genotypes do not associate with any abnormality except the homozygous GG have higher triglycerides and lower HDL-C. Interestingly, glucose showed different correlation patterns in individuals carrying different genotypes of the two studied SNP, indicating clearly that the metabolic responses to a normal nutrient are significantly influenced by the genotypes of the SNPs in ADRB2.
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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.
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Biomarcadores/sangue , Resistência à Insulina , Obesidade/fisiopatologia , Síndrome do Ovário Policístico/epidemiologia , Adulto , Índice de Massa Corporal , Estudos de Casos e Controles , Estudos Transversais , Feminino , Hormônio Foliculoestimulante/sangue , Seguimentos , Grelina/sangue , Humanos , Insulina/sangue , Hormônio Luteinizante/sangue , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/patologia , Prognóstico , Estudos Prospectivos , Globulina de Ligação a Hormônio Sexual/metabolismo , Testosterona/sangue , Adulto JovemRESUMO
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.
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Hiperinsulinismo/genética , Hipertrigliceridemia/genética , Leptina/sangue , Obesidade/sangue , Obesidade/genética , Polimorfismo Genético , Adolescente , Adulto , Substituição de Aminoácidos , Antropometria , Índice de Massa Corporal , Feminino , Frequência do Gene , Estudos de Associação Genética , Humanos , Lipídeos/sangue , Masculino , Reação em Cadeia da Polimerase , Arábia Saudita , Adulto JovemRESUMO
"Residual ridge resorption" (RRR) is a multifactorial condition involving bone resorption of the residual ridge. We investigated 10 single nucleotide polymorphisms (SNPs) in seven genes with the aim of identifying the genetic factors associated with RRR susceptibility. The study group included 96 RRR patients and 96 controls. Age at first edentulism, duration of edentulism, and bone height were recorded. Saliva was collected from the subjects for DNA extraction. Genotype analysis was performed on the 'SequenomMassARRAYiPLEX'. The genotype and allele frequencies calculated in patients and controls were compared. We found that rs1800896 in the IL10 gene and rs5743289 in NOD2 gene showed significant association with RRR. Within the RRR group, genotypes for each SNP were separated, and we observed that the age at first edentulism and bone height showed variations in the different genotypes of the ten studied SNPs. This study showed an association between SNPs in IL10 and NOD2 genes. It also revealed that the genotypes of the different SNPs influence bone resorption and health. Additionally, age at first edentulism and bone height were much lower in some genotypes. This study demonstrates the need for larger multicenter trials to confirm these findings. Finally, we suggest that the results of this study may be utilized for developing novel genetic diagnostic tests and for identifying Saudi individuals who may be more susceptible to RRR development following dental extraction.
RESUMO
The Gln233Arg (A>G; rs1137101) polymorphism of the leptin receptor gene (LEPR) has been investigated extensively and is reported to be associated with different metabolic states. In this investigation, we aimed to study the frequency of Gln233Arg genotypes and alleles in a group of Saudi women stratified by their body mass index (BMI), to correlate the LEPR genotypes with variations in anthropometric, lipid and hormonal parameters and to investigate conformational and structural variations in the mutant LEPR using molecular dynamic (MD) investigations. The study group included 122 Saudi women (normal weight = 60; obese = 62) attending the clinics for a routine checkup. Anthropometric data: height, weight, waist and hip circumference were recorded and fasting serum sample was used to estimate glucose, lipids, ghrelin, leptin and insulin. BMI, W/H ratio, and HOMA-IR values were calculated. Whole blood sample was used to extract DNA; exon 6 of the LEPR gene was amplified by PCR and sequencing was conducted on an ABI 3100 Avant Genetic Analyser. Molecular Dynamic Simulation studies were carried out using different softwares. The results showed the presence of all three genotypes of Gln233Arg in Saudi women, but the frequencies were significantly different when compared to reports from some populations. No differences were seen in the genotype and allele frequencies between the normal weight and obese women. Stratification by the genotypes showed significantly higher BMI, waist and hip circumference, leptin, insulin, fasting glucose and HOMA-IR and lower ghrelin levels in obese women carrying the GG genotype. Even in the normal weight group, individuals with GG genotype had higher BMI, waist and hip circumference and significantly lower ghrelin levels. The MD studies showed a significant effect of the Gln/Arg substitution on the conformation, flexibility, root-mean-square fluctuation (RMSF), radius of gyration (Rg) values, solvent-accessible surface area (SASA) and number of inter- and intra-molecular H-bonds. The results suggest that the structural changes brought about by the mutation, influence the signaling pathways by some unknown mechanism, which may be contributing to the abnormalities seen in the individuals carrying the G allele of rs1137101.
Assuntos
Proteínas Mutantes/química , Proteínas Mutantes/genética , Obesidade/genética , Polimorfismo de Nucleotídeo Único , Receptores para Leptina/química , Receptores para Leptina/genética , Adulto , Substituição de Aminoácidos , Índice de Massa Corporal , Peso Corporal/genética , Estudos de Casos e Controles , Éxons , Feminino , Frequência do Gene , Humanos , Ligação de Hidrogênio , Resistência à Insulina/genética , Metaboloma/genética , Simulação de Dinâmica Molecular , Obesidade/metabolismo , Arábia Saudita , Circunferência da Cintura/genética , Adulto JovemRESUMO
PURPOSE: The purpose of this clinical and radiographic study was to evaluate the effect of age, gender and duration of edentulism on the amount of mandibular residual ridge resorption in a Saudi population. MATERIAL AND METHODS: Partially and completely edentulous Saudi patients (50 male and 64 female) attending the outpatient clinics at College of Dentistry, King Saud University, Riyadh, Saudi Arabia were included. Current age, gender of subjects and date of start of edentulism were recorded. Digital panoramic dental radiograph less than 1â¯year old of each patient was examined. The height of edentulous mandible was measured as described in the American College of Prosthodontists Prosthodontic Diagnostic Index (PDI) classification. Students t-test and ANOVA post hoc tests, Pearson's correlation coefficient (r) and chi square (χ2) analysis were performed as indicated. Level of statistical significance was set at 0.05. RESULTS: Male patients showed a significantly greater mandibular bone height compared to female patients. Age and bone height were statistically significantly negatively correlated (pâ¯=â¯0.0001). However, age and mandibular bone height in only male patients was negatively correlated and reached statistical significance (pâ¯=â¯0.001) A negative correlation was observed between duration of edentulism and mandibular bone height in both genders, but was not statistically significant (pâ¯>â¯0.05). CONCLUSIONS: In a Saudi population, men have greater mandibular bone height than women and also exhibit a negative correlation between age and mandibular bone height that is statistically significant. In contrast, women exhibited a negative correlation between age and mandibular bone height, but was not statistically significant.
RESUMO
BACKGROUND: Mutations in BRCA1 gene have been implicated in ovarian cancers, and BRCA testing may be conducted in high-risk women. This study was designed to determine the frequency of three single nucleotide polymorphisms (SNPs) variants in BRCA1 gene and BRCA1 expression in Saudi females with ovarian cancer. METHODS: Expression levels of mRNA of BRCA1 gene were studied in 10 ovarian cancer and 10 normal ovarian tissues, by quantitative real time polymerase chain reaction (qPCR). The study also included 28 females who had suffered from ovarian cancer and had been successfully operated upon and 90 healthy females with no history of cancer. Blood was drawn in EDTA tubes and used for extraction of DNA. The genotyping was carried out using Taqman® SNP Genotyping kit by RT-PCR. The variants investigated included c.871 T>C (rs799917), c.1040 G>A (rs4986852), c.181 T>G (rs28897672) in BRCA1 gene. RESULTS: The c.181 T>G (rs28897672) showed significantly different genotype and allele frequencies between the patients and the control subjects (p value = 0.002 and 0.02, respectively). The genotype TG was significantly protective (OR = 0.36, p value = 0.024). The mRNA expression of BRCA1 gene was found to be low in the ovarian cancer tissues. CONCLUSIONS: This study showed that c.181 T>G in BRCA1 genes is associated with the development of ovarian cancer in Saudis. More studies are needed to unveil other SNPs that may be associated with ovarian cancer and to understand the mechanism(s) involved in reducing the expression of BRCA1 gene in ovarian cancer tissues.