Genotype Distribution Of Polymorphism Research Articles

Association analysis between CD14 gene polymorphisms and peri-implantitis susceptibility in a Chinese population.

The goal of the study was to examine the genetic correlation of cluster of differentiation 14 (CD14) gene polymorphisms with peri-implantitis (PI) predisposition in a Chinese Han population. In the case-control study, blood samples were collected from PI patients and healthy individuals (n = 120/group), who were admitted to the Affiliated Hospital of Yangzhou University from 2021 to 2023. One-way analysis of variance (ANOVA) was applied to compare differences of continuous variables among different groups. Genotype and allele distributions of CD14 gene rs2569190 and rs2915863 polymorphisms were analyzed between groups via χ2 test. A high percentage of rs2569190 GG genotype or G allele carriers were identified in PI group compared with control group (p < .01). Rs2569190 GG genotype carriers had high risk to develop PI (odds ratio: 2.545, 95% confidence interval: 1.257-5.156, p = .009). The rs2569190 AA genotype carriers had the lowest values of gingival index, plaque index, calculus index, peri-implant pocket depth, and clinical attachment level, which were the highest in cases with GG genotype. Rs2569190 polymorphism of CD14 gene was significantly associated with PI predisposition in the Chinese Han population, and the GG genotype and G allele were risk factors for the development of PI.

The effect of leptin gene polymorphisms (LEP rs7799039 and LEPR rs1137101) on febrile neutropenia

Background and aimLeptin is mainly produced in adipose tissue and released into systemic circulation. Leptin and its receptor LEPR activate the Janus kinase/signal transducers and activators of transcription signaling cascade and increase cytokine discharge. In our study, we aimed to examine the role of leptin gene (LEP) rs7799039 and LEPR rs1137101 polymorphisms on the susceptibility for febrile neutropenia (FEN) attacks and their relationship with clinical findings during the course of FEN. MethodsThis study included pediatric patients with a diagnosis of malignancy who applied to the pediatric emergency department between December 2019 and June 2022 and healthy controls. The genotypes of the LEP rs7799039 and LEPR rs1137101 genes were statistically compared between patients and healthy controls. In addition, the relationship between the genotype distribution of LEP rs7799039 and LEPR rs1137101 polymorphisms and clinical features during the course of FEN was investigated. ResultsIn the statistical analysis in terms of LEP rs7799039 and LEPR rs1137101 genotype distributions between the patient and healthy groups, there was no significant difference. Patients with the AA genotype of LEPR rs1137101 polymorphism had significantly more commonly a body mass index (BMI) value of <25, and all the patients with the AG/GG genotype had a BMI value of 25 and above. LEP rs7799039 and LEPR rs1137101 genotype distributions were not statistically significant with other clinical features. ConclusionsIt was revealed that leptin gene polymorphisms did not have a significant effect during the course of FEN.

Association of combined -344T/C and K173R polymorphisms in aldosterone synthase gene with type 2 diabetes mellitus in the Moroccan population.

Background: Aldosterone synthase (CYP11B2) is crucial for aldosterone production, and variations in its gene may influence type 2 diabetes mellitus (T2DM) development. This study explores the link between two single nucleotide polymorphisms (SNPs) in the CYP11B2 gene - -344T/C and K173R and T2DM in the Moroccan population . Methods: The research involved 86 individuals with T2DM and 75 control subjects. Genotyping for the -344T/C and K173R SNPs was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis . Result: Results indicated significant differences in the genotype and allelic distribution of the CYP11B2 K173R polymorphism between T2DM patients and control subjects, with P-values of 0.02 and 0.04, respectively. The -344T/C polymorphism showed no significant genomic level differences, but its allelic variations were statistically significant (P=0.01), indicating a notable association between the C allele and T2DM. Furthermore, the K173R polymorphism was found to significantly increase T2DM risk, with a 2.34-fold higher risk in individuals carrying the KR genotype. The study also examined the combined effect of these SNPs. The dominant model analysis (TT vs. TC+CC and KK vs. KR+RR) showed significant differences between T2DM patients and controls for both SNPs. Additionally, a haplotype-based analysis revealed that the C-R haplotype was associated with an increased risk of T2DM. Conclusion: Our study suggests a significant association between the CYP11B2-K173R polymorphism and T2DM in the Moroccan population. Conversely, while the CYP11B2 -344T/C polymorphism exhibits a significant difference in allelic distribution, no significant difference is observed at the genomic level.

Association of OX40L gene polymorphism with multiple sclerosis in Iranians

IntroductionThe exact etiology of multiple sclerosis is unknown but recent studies indicated a link between tumor necrosis factor superfamily member 4 and the disease. Polymorphisms located in the regulatory region of the gene may affect its phenotype. Hence, we aimed to investigate the association of promoter polymorphisms of the gene with multiple sclerosis and also to estimate the frequency of haplotypes in the patients and healthy subjects. MethodsTwo hundred age- and sex-matched subjects including 100 patients and 100 healthy subjects were investigated in the study. Genotype and allele distributions of rs3850641, rs1234313, and rs10912580 polymorphisms in the promoter region of the gene were investigated by polymerase chain reaction-restriction fragment length polymorphism. In addition, haplotype frequencies estimation and linkage disequilibrium analysis were performed by SNPStats web tool. ResultsThe distribution of AA, AG and GG genotypes of rs3850641 was significantly different between the patient and healthy groups (P = 0.009). In addition, frequencies of A and G alleles of rs3850641 were different between the groups (P < 0.001). Also the distribution of rs3850641 genotypes was different between the women of the both groups (P = 0.007). Our analysis revealed that rs3850641 AG (Odds ratio = 0.393, 95 % confidence interval = 0.170–0.907, P = 0.029) and GG (Odds ratio = 0.373, 95 % confidence interval = 0.168–0.830, P = 0.016) genotypes were associated with decreased risk of the disease. However, rs1234313 genotype and allele distributions were not different between the groups. The distribution of rs10912580polymorphism. AA, AG, and GG genotypes was significantly different between the groups (P = 0.007). rs10912580 AG genotype was associated with low risk of the disease (Odds ratio = 0.252, 95 % confidence interval = 0.102–0.623, P = 0.003). The distribution of haplotypes was statistically different between the patient and healthy groups (P < 0.001). A-G-A was the most frequent haplotype among the patients and the estimated frequency was higher than that of the control group (0.5527 versus 0.3739). ConclusionThe distribution of rs3850641 and rs10912580 genotypes was different between the patients and healthy subjects. Moreover, rs3850641 AG and GG genotypes and also rs10912580 AG genotype were associated with low risk of the disease in Iranians. Further studies with large groups are recommended to show whether genotype variation in the patients could alter the response to treatment or not.

The Association Between Genetic Variants in ACE1and ACE2 Genes with Susceptibility to COVID-19 Infection.

Angiotensin-converting enzyme 2 (ACE2) receptors facilitate the entry of the causative virus severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) into target cells. Some ACE gene variants have been suggested to be involved in COVID-19 pathogenesis. So, the aim was to assess the association between ACE1 rs4646994 and ACE2 rs2285666 genes polymorphisms and the susceptibility and severity of COVID-19. This case-control study was conducted on 197 patients with COVID-19 and 197 healthy controls. ACE-1 insertion/deletion (I/D) (rs4646994) and ACE2 rs2285666 genes polymorphisms were determined by the amplification refractory mutation system- polymerase chain reaction (ARMS-PCR) technique. The DD genotype of ACE1 I/D polymorphism was associated with increased susceptibility to COVID-19 infection (p = 0.012), whereas the ID genotype of this polymorphism was associated with decreased susceptibility (p = 0.003) (significance level = 0.017). There was no significant association in allele and genotype distribution of ACE2 rs2285666 polymorphism between cases and controls. The ACE1 I/D polymorphism may be considered as a risk factor for COVID-19 susceptibility.

Association of polymorphism (RS1800896) of IL-10 gene and IL-10 gene expression in ovarian cancer patients from Georgia

Background/Aim: Ovarian cancer is one of the most important causes of tumour-associated mortality and morbidity in women. Some genetic alterations, determining predisposition to ovarian cancer have already been identified, but these are mostly syndrome-associated cases, most ovarian tumours are still regarded as sporadic. The aim of this research was to identify new predisposing factors that might increase ovarian cancer risk. Genetic variants of IL-10 gene in patients with ovarian cancer was analysed. Methods: Forty-eight patients with ovarian cancer along with 48 agematched controls were included in the study. Single nucleotide polymorphism (SNP) genotyping and gene expression assays for IL-10 were performed using TaqMan assay (Thermo Scientific, USA). The selected SNP was rs1800896 upstream of IL-10 gene (IL-10-1082). All statistical analyses were performed by GraphPad Prism 9.3.1 for Mac. Results: The genotype distributions of IL-10 gene polymorphisms among cancer and control groups were all according to the expected Hardy-Weinberg equilibrium. There was no statistically significant difference in frequency of genotypes and alleles between the two study groups (p &gt; 0.05). In another analysis, the samples were grouped according to the polymorphic variant IL-10 (-1082) A/G. Subjects having the homozygous variant (A/A) had lower IL-10 mRNA levels than those with the homozygous wild (G/G) genotype in both, ovarian cancer patients and controls, p &lt; 0.05. mRNA levels on IL-10 were different among cases and controls (p &lt; 0.05). Patients with ovarian cancer had higher level of mRNA for IL-10. Conclusions: These results support the theory that IL-10 gene expression levels differ in patients with and without ovarian cancer. Polymorphic variant IL-10 (-1082) A/G couldn't be confirmed to explain this difference in gene expression levels.

Genetic Variants Associated with High Susceptibility of Premature Ischemic Stroke.

Several polymorphisms had been associated with an increased risk of ischemic stroke, but results are inconclusive. The aim of this study was to examine the association between AGTR1 A1166C and TSP-1 N700S polymorphisms and ischemic stroke in a young Mexican population. In a case-control study, 250 patients ≤ 45 years of age with ischemic stroke and 250 controls matched by age and gender were included. The polymorphisms were determined in all participants by polymerase chain reaction. There were statistical differences in genotype distribution (p = 0.01) and allele frequency (p = 0.001) of AGTR1 A1166C polymorphism. In contrast, there was a similar genotype distribution (p = 0.96) and allele frequency (p = 0.76) of the TSP1 N700S genetic variant between groups. Hypertension (p = 0.03), smoking (p = 0.02), and family history of atherothrombotic disease (p = 0.04) were associated with stroke, but not diabetes (p = 0.30) and dyslipidemia (p = 0.08). This is the first study in Mexican population to explore several genetic variants in young patients with ischemic stroke. Our results suggest that polymorphisms in the renin-angiotensin-aldosterone system could contribute to premature hypertension, endothelial dysfunction, atherothrombosis, vasoconstriction, smooth muscle cell migration, and proliferation. In contrast, polymorphisms in the coagulation factors are not associated with ischemic stroke. Environmental factors such as diabetes and dyslipidemia could be less important in the pathogenesis of ischemic stroke at a young age. We suggest that those polymorphisms should be determined in individuals with a family history of thrombosis to avoid the stroke development. Therefore, genotype-environmental combination could determine several possible phenotypes at different moments in life.

The association between MMP-13 rs478927 gene polymorphism and dental caries susceptibility in children with mixed dentition from Birjand, Iran: A case-control study.

Gene polymorphisms are responsible for at least part of the variation in caries susceptibility despite similar environmental factors. Genes involved in enamel formation like matrix metalloproteinase-13 (MMP-13) may participate in caries process. The aim was to investigate the association between MMP-13 rs478927 polymorphism and caries susceptibility in 6-years-old children from Birjand, Iran. Six-years old children from Birjand, Iran, participated in this study. The total decayed, missing, and filled teeth were calculated and defined as caries index (CI). Based on this CI, two groups of high-caries (case) and low-caries (control) were taken into account. Saliva samples were collected and DNA was extracted. The allele and genotypes of MMP-13 rs478927 polymorphism were determined by tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) method. p Value was significant if p < 0.05. Three hundred sixty-seven children consisted of 186 low-caries children and 181 high-caries children were included in this study. The mean CI was 6.02 ± 0.81. There was no significant association between high and low-caries groups based on socioeconomic status, eating sweet snacks, parents' susceptibility to dental caries, duration of breastfeeding, and the brushing habit (p > 0.05). There wasn't any significant association between genotype distribution of MMP-13 rs478927 polymorphism and CI groups (p = 0.924). This polymorphism was associated with increased caries susceptibility under all genetic models but this effect was not significant (p > 0.05). The MMP-13 rs478927 gene polymorphism was not significantly associated with dental caries susceptibility in Birjandi children with mixed dentition. It is recommended to conduct studies on children of different dentitions to better understand the role of this polymorphism on caries susceptibility in primary and permanent teeth of children.

Genetic association of PTPN22 polymorphisms with Type 1 diabetes in Pakistani children

ObjectiveType 1 diabetes, a multigenic autoimmune disorder, is caused by the destruction of pancreatic beta-cells leads to insufficient insulin production and hyperglycemia, resulting in early morbidities and mortality. This study was designed to explore the genetic association of PTPN22 gene polymorphisms with T1D susceptibility among Pakistani children. MethodsBlood samples of T1D patients were obtained from the Department of Diabetes and Endocrinology of Children Hospital & University of Child Health Sciences, Lahore. Genotyping of rs2476601, rs1310182, and rs1217414of the PTPN22 gene was performed by Tetra ARMS-PCR assay. Statistically, binary logistic regression was applied to determine variation in genotype distribution and association of PTPN22 gene polymorphism with T1D. ResultsGenetic analysis showed that the A allele of rs2476601 (OR = 0.53, 95 % CI = 0.31–0.90; P < 0.02) and T allele of rs1310182 was found to be risk allele for T1D development (OR = 0.51, 95 % CI = 0.36–0.76; P < 0.01) while the A allele of rs1217414 was a protective allele against T1D (OR = 1.19, 95 % CI = 0.80–1.77; P = 0.36). Genetic models revealed that GG genotypes of rs2476601 (OR = 2.01, 95 % CI = 1.13–3.58; P < 0.01), and AA genotypes of rs1310182 in the dominant model (OR = 1.83, 95 % CI = 1.03–3.24; P < 0.03) showed significant risk association with T1D. ConclusionFrom the results, it is concluded that PTPN22gene has a strong genetic association with SNP rs2476601andrs1310182with T1D in Pakistani children.

Association between interleukin-12B gene polymorphisms and multiple sclerosis in turkish population

Elevated levels of IL-12p40 have been observed in the cerebrospinal fluid and serum of MS patients, and it has been suggested that genetic variants in the IL-12B gene may contribute to MS susceptibility and/or pathogenesis. In this study, we investigated the association between MS and IL-12B gene rs17860508 and rs3212227 polymorphisms in the Turkish population. We identified two polymorphic regions in the IL-12B gene using bioinformatics tools and genotyped 351 MS patients and 221 healthy controls for these variants. Our results showed a significant association between the IL-12B rs17860508 polymorphism and MS, but no significant relationship between rs17860508 genotype distribution and allele frequency and MS age onset or subtypes. Genotype distribution and allele frequency of IL-12B rs3212227 polymorphism did not show any significant association with MS directly. However, AC genotype of IL-12B rs3212227 polymorphism in early-onset multiple sclerosis (EOMS) was a risk factor according to age of onset. Additionally, we observed a higher risk for the relapsing-remitting multiple sclerosis (RRMS) subtype in females. This is the first study to investigate the association between IL-12B polymorphisms and MS in the Turkish population.

FTO gene variants (rs9939609, rs8050136 and rs17817449) and type 2 diabetes mellitus risk: A Meta-Analysis

Background and aimsThere is tremendous increase in type 2 diabetes mellitus (T2DM) worldwide. The impact of FTO gene polymorphisms on the risk of T2DM is not yet clear because of the controversial results of studies. This meta-analysis aimed to better clarify the association between three FTO gene polymorphisms SNPs (rs9939609, rs8050136 and rs17817449) and T2DM in a larger combined population worldwide. Material and methodsA comprehensive search on the PubMed, Science Direct, and Web of Science databases was conducted to identify investigations in relationship between different FTO gene polymorphisms (rs9939609, rs8050136 and rs17817449) and T2DM globally. Published papers from January 2007 to May 2023 were collected. Inclusion criteria are limited to human case-control studies published in English and peer-reviewed, which provided data on the genotype distributions of FTO gene polymorphisms and T2DM risk. Odds ratios (OR) and 95% confidence intervals (CI) were calculated to express the results of the meta-analysis. Potential sources of bias and heterogeneity using Egger's regression analysis were also assessed. ResultsOf 234695 identified articles, forty-eight studies were selected including 36,051 patients with T2DM and 51,266 control subjects. Overall, we found a significant increased risk of T2DM susceptibility and rs9939609 FTO gene polymorphism in the Allele contrast (A vs. T: OR = 1,30, 95% CI = 1.14; 1.48, P < 0,05, I2 = 0,94), Recessive model (AA vs. AT + TT: OR = 1,54, 95% CI = 1.19; 2.00, P < 0,05, I2 = 0,94), Dominant model (AA + AT vs. TT: OR = 1,26, 95% CI = 1.10; 1.45, P < 0,05, I2 = 0,89), homozygote model (AA vs. TT: OR = 1,60, 95% CI = 1.26; 2.03, P < 0,05, I2 = 0,90), and heterozygote model (AA vs. AT: OR = 1,43, 95% CI = 1.09; 1.88, P = 0,008, I2 = 0,93). we also found a significantly increased risk of T2DM susceptibility and rs8050136 FTO gene polymorphism under all models. For rs17817449 we did not find any association between with T2DM. ConclusionThe present meta-analysis confirms that rs9939609 and rs8050136 in the FTO gene are significantly associated with T2DM, while rs17817449 does not show any association.

ABCA3 and LZTFL1 Polymorphisms and Risk of COVID-19 in the Czech Population.

SARS-CoV-2 infection, which causes the respiratory disease COVID-19, has spread rapidly from Wuhan, China, since 2019, causing nearly 7 million deaths worldwide in three years. In addition to clinical risk factors such as diabetes, hypertension, and obesity, genetic variability is an important predictor of disease severity and susceptibility. We analyzed common polymorphisms within the LZTFL1 (rs11385942) and ABCA3 (rs13332514) genes in 519 SARS-CoV-2-positive subjects (164 asymptomatic, 246 symptomatic, and 109 hospitalized COVID-19 survivors) and a population-based control group (N?=?2,592; COVID-19 status unknown). Rare ABCA3 AA homozygotes (but not A allele carriers) may be at a significantly increased risk of SARS-CoV-2 infection [P?=?0.003; OR (95 % CI); 3.66 (1.47-9.15)]. We also observed a borderline significant difference in the genotype distribution of the LZTFL1 rs11385942 polymorphism (P?=?0.04) between the population sample and SARS-CoV-2-positive subjects. In agreement with previous studies, a nonsignificantly higher frequency of minor allele carriers was detected among hospitalized COVID-19 subjects. We conclude that a common polymorphism in the ABCA3 gene may be a significant predictor of susceptibility to SARS-CoV-2 infection.

IL12B and IL17 genes polymorphisms associated with differential susceptibility to juvenile idiopathic arthritis and juvenile-onset systemic lupus erythematosus in Chinese children

Genetic factors play a crucial role in the immune response of juvenile idiopathic arthritis (JIA) and juvenile-onset systemic lupus erythematosus (JSLE). This study aimed to investigate the association of IL12B (rs3212227, rs6887695) and IL17 (rs2275913, rs763780) gene polymorphisms with the susceptibility of JIA and JSLE in Chinese children. A total of 303 healthy controls and 304 patients including 160 JIA and 144 patients were analyzed, and the genetic polymorphisms were genotyped by using a Sequenom MassArray system. There was a significant association between the IL12B rs3212227 genotype and the increased risk of JSLE (P = .01). For rs6887695, the minor allele C was significantly associated with the increased risk of JIA (odds ratio = 1.48, 95% confidence interval [CI] = 1.12–1.95, P = .005). Moreover, rs6887695 genotype was significantly associated with both JIA and JSLE susceptibility (P &lt; .05). Besides, IL12B haplotype GC significantly associated with the increased risk of JIA (P = .016). However, no significant difference was found between the IL17 (rs2275913, rs763780) gene polymorphisms and JIA or JSLE susceptibility (P &gt; .05). And similar genotype distributions of IL12B and IL17 polymorphisms were found between the patients with nephritis and without nephritis in JSLE (P &gt; .05). Our results indicated that IL12B polymorphisms was associated with an increased risk for the development of JIA and JSLE in Chinese children, highlighting the involvement of inflammation in the pathogenesis of JIA and JSLE. Moreover, there was a risk haplotype in IL12B which could increase the risk of JIA.

The Role of Angiotensin II Type 1 Receptor A1166C Polymorphism in Autosomal Dominant Polycystic Kidney Disease.

Introduction Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic disorder that affects the kidney, which affects all ethnical groups worldwide, with varied clinical presentations and severity. The studies done in various parts of the world on the association between angiotensin II type 1 receptor (AT1R) A1166C gene polymorphism and ADPKD patientshave revealed inconsistent results. This study was done to assess the role of AT1R A1166C gene polymorphism in ADPKDin the South Indian population, which is the first of its kind. Methodology This is a case-control study, conducted at a tertiary care centerin South India. This study was concerned with the frequency of exposure (genotype) in ADPKD patients. Peripheral blood samples from 85 unrelated ADPKD patients and 94 controls without diabetes, hypertension, or any kidney-related disease were collected. The AT1R A1166C polymorphism was compared between (i) the cases and controls, (ii) early and late stages of chronic kidney disease(CKD) (ADPKD) subjects, and (iii) ADPKD subjects with and without hypertension. Results Among the ADPKD patients, 45 (52.9%) subjects showed early stage (CKD stages 1-3), and 40 (47%) subjects showed late stage CKD (CKD stages 4 and 5). The genotype distribution of the studied 85 ADPKD patients was almost similar. No significant association was found between the genotype distribution of AT1R A1166C polymorphism in AA vs. AC (OR = 1.11; 95% CI = 0.37-3.32; p < 0.844) and A vs. C (OR = 1.11; 95% CI = 0.38-3.32; p < 0.847) between cases and controls. The genotype distributions in genetic model AA vs. AC (OR = 3.07; 95% CI = 0.56-16.8; p < 0.177) and allelic model A vs. C (OR = 2.13; 95% CI = 0.40-11.3; p < 0.364) between the early and late CKD stages of ADPKD were also not significant. No significant association of gene polymorphism was found between the non-hypertensive and hypertensive groups of ADPKD. Conclusion The results of our study suggest there is no significant association between AT1R A1166C polymorphisms and ADPKD in the South Indian population. Further, the gene polymorphism is not related to the progression of ADPKD or the presence of hypertension in ADPKD cases in South India.

The Investigation of Lectin-Like Oxidized LDL Receptor 1 (LOX-1) K167N Polymorphism, Inflammation, and Lipid Status in Patients with Coronary Artery Bypass Grafting

Objective: Coronary artery disease (CAD) is a pathological condition resulting from atherosclerosis in the coronary arteries. Besides traditional risk factors, genetic factors such as single nucleotide polymorphs (SNPs) can be involve in disease process. Inflammation plays a role in pathological changes throughout atherosclerosis, from initiation to progress. In this study, we aimed to evaluate the effects of lectin-like oxidized LDL receptor 1 (LOX-1) K167N polymorphism, inflammation, and lipid status in patients with coronary artery bypass grafting (CABG). Material and Methods: The study population consisted of 129 CAD patients who had undergone CABG, and 71 healthy controls. The LOX-1 K167N polymorphism was genotyped using PCR-RFLP technique. Plasma interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin-33 (IL-33) levels were determined by enzyme-linked immunosorbent assay (ELISA) kits. Results: The distribution of the LOX-1 K167N genotypes and alleles did not differ significantly between CAD patients with CABG and controls. There were no significant differences in plasma IL-1β, TNF- α, IL-33, HDL-C, and LDL-C levels between the patients and controls. IL-1β and systolic blood pressure values were significantly higher in KK genotype patients compared to the same genotype controls(P&lt;0.05). Similarly, systolic blood pressures were higher in NK genotype patients compared with NK genotype controls (P&lt;0.01). Conclusions: IL-1β and systolic blood pressure values were found to be higher in post CABG CAD patients with the KK genotype compared to healthy controls with the same genotype while inflammatory markers and lipid profiles selected according to LOX-1 K167N polymorphism genotype and allele distributions did not differ between groups. Although we couldn’t find an assocation between LOX-1 K167N polymorphism and CAD other than high BP in our study, studies with larger sample sizes might reveal such a relation.

#3145 ASSOCIATION OF ENDOTHELIAL NITRIC OXIDE SYNTHASE GENE POLYMORPHISM WITH ENDOTHELIAL DYSFUNCTION IN DIABETIC NEPHROPATHY AMONG AZERBAIJANIS

Abstract Background and Aims Vascular endothelial dysfunction resulting from impaired nitric oxide synthase (NOS) activity in the endothelial cells of blood vessels has been suggested as playing an important role in the pathogenesis of Diabetic nephropathy (DN). It regulates endothelial function and maintains endothelial-dependent vasodilation in multiple organs, including the kidney. The study was carried out to investigate the association of T-786C single nucleotide polymorphisms with the flow mediated dilation (FMD) in DN among type 2 diabetic subjects. Method 90 patients (45 male and 45 female) with diabetic nephropathy were recruited from Nephrology and Endocrinology departments of the Azerbaijan Medical University hospital. As a control group the results were compared with the findings in 100 healthy Azerbaijani individuals (50 males and 50 females). The study was approved by ethics committee and informed consent was obtained from all patients in written form. Brachial endothelial function was determined by brachial artery vasodilator response or brachial FMD in the dominant arm according to previously validated techniques. T786C polymorphism was detected using polymerase chain reaction-restriction fragment length polymorphism analysis. Results The results showed significant differences between DN group and control group regarding the genotype and allele distributions of the T786C single nucleotide polymorphisms. The CC genotype was significantly more frequent in diabetics nephropathy patients than in control group (42% vs. 8%, p = 0.01). FMD in allele homozygote T786C(TT), T786C(CC) and heterozygote T786C(CT) were respectively 13.5 ±0.16%, 12.3±0.19%,13.9 ±0,28%. In the study groups, Azerbaijani patients showed dominance of the C allele and a mutant homozygous genotype CC of the T786C gene of eNOS. Subjects with the 786C(CC) (n = 48) showed significantly reduced FMD with those with T786C (TT) (n = 7) (p = 0.021) and T786C (CT) (n = 35) (p = 0.023), whereas there was no significant difference in endothelial-independent vasodilation between these groups. Although subjects with homozygote T786C(TT), did not show significantly reduced levels of FMD. Who were carriers of the T786C allele demonstrated markedly reduced levels of FMD compared with noncarriers (p = 0.019). Conclusion The data suggest that in diabetic nephropathy, the eNOS T786C allele may be involved in endothelial dysfunction. Azerbaijani patients showed dominance of the C allele and a mutant homozygous genotype CC of the T786C gene of eNOS.

Association Between Follicle-Stimulating Hormone Receptor (FSHR) rs6166 and Estrogen Receptor 1 (ESR1) rs2234693 Polymorphisms and Polycystic Ovary Syndrome Risk, Phenotype, and Reproductive Outcomes in an Infertile Portuguese Population.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder often leading to anovulatory infertility. PCOS pathophysiology is still unclear and several potential genetic susceptibility factors have been proposed. The effect of polymorphisms in two genesrelated to follicular recruitment and development, the follicle-stimulating hormone receptor (FSHR) and the estrogen receptor 1 (ESR1), have been studied in different populations with contradictory results. To evaluate the influence of FSHR rs6166 (c.2039A>G) and of ESR1 rs2234693 (Pvull c.453-397 T > C) polymorphisms on PCOS risk, phenotype, and response to controlled ovarian stimulation (COS). Genotyping of the FSHR rs6166 andthe ESR1 rs2234693 polymorphisms was performed inPCOS women and a control group undergoing in vitro fertilization (IVF). Demographic, clinical, and biochemical data, genotype frequency, and IVF outcomes were compared between groups. We evaluated 88 PCOS women and 80 controls. There was no significant difference in the genotype distribution of FSHR rs6166 polymorphism between PCOS women and controls (AA 31.8%/AS 48.9%/SS 19.3% in PCOS women vsAA 37.5%/AS 40.0%/SS 22.5%in controls; p = 0.522). The same was true for the ESR1 rs2234693 (CC 24.1%/CT 46.0%/TT 29.9% in PCOS women vsCC 18.8%/CT 48.8%/TT 32.5%in controls; p = 0.697).In PCOS women, we found higher follicle-stimulating hormone (FSH) levels on the third day of the menstrual cycle associated with the SS variant of the FSHR polymorphism (9.2 vs6.2 ± 1.6 and 5.6 ± 1.6 mUI/mL; p = 0.011). We did not find other associations between the baseline hormonal parameters, antral follicle count, and response measures to COS with FSHR or ESR1 genotypes. We found, however, a need for higher cumulative doses of FSH for COS in patients with the SS variant of the FSHR rs6166 polymorphism (1860.5 ± 627.8 IU for SSvs1498.1 ± 359.3 for AA and 1425.4 ± 474.8 for SA; p = 0.046 and p = 0.046). Our data suggest thatin the population,FSHR rs6166and ESR1 rs2234693 polymorphisms do not influence the risk of developing PCOS nor do they influence the patient's phenotype and IVF success. However, the SS variant of the FSHR rs6166 polymorphism may beassociated with FSH resistance requiring higher FSH doses for COS.

Genetic Association of VDR gene Apa1 and Taq1 Variants with Scleroderma in an Iranian Northeast Population.

Despite vigorous research efforts, the etiology of scleroderma (systemic sclerosis (SSc)) remains still unclear and both genetic and environmental factors clearly contribute to the pathogenesis of scleroderma. Reports of aberrant vitamin D status in scleroderma patients suggest a need for considering the genotype and allele frequencies of VDR gene polymorphisms. This case-control study aimed to investigate the possible association of two common polymorphisms of the VDR gene (ApaI, and TaqI) with susceptibility to scleroderma in an Iranian population. Using polymerase chain reaction and restriction fragment length polymorphism (PCRRFLP), ApaI and TaqI polymorphisms in the VDR region were genotyped in 51 patients with scleroderma and 50 healthy controls. Logistic regression analysis was performed to calculate the genotypes odds ratios (ORs) as a measure of association with the presence of scleroderma. Haplotype and linkage disequilibrium analyses were also performed on the detected genotypes. No significant differences were found for the allelic and genotype distributions of ApaI and TaqI polymorphisms between patients with scleroderma and healthy controls (p>0.05). In haplotype analysis, three haplotypes TA, CA, and TC, with a frequency greater than 1% were identified. However, none of them was associated with the risk of scleroderma. Our preliminary study showed no evidence of an association between ApaI and TaqI polymorphisms and scleroderma. As the association between VDR polymorphisms and autoimmune diseases varies across the different ethnic populations, further large cohort studies are necessary to confirm the results.

Estimating the role of single-nucleotide polymorphism (rs1800629)-308 G/A of TNF-alpha gene as genetic marker associated with angina pectoris in a sample of Iraqi patients

BackgroundAngina pectoris (AP) occurs when oxygen and other nutrients are insufficient to meet the metabolic needs of the heart muscle. Stable angina is the most common, while the unstable angina is less frequent. Tumor necrosis factor alpha (TNF-alpha) is a pleiotropic cytokine plays a vital function in the immune response regulation. TNF gene cluster contains many polymorphisms; the most commonly investigated polymorphism is the rs1800629 SNP. This SNP, located at − 308 position with regard to the TNF promoter region, replaces guanine (G) with adenine (A), with the allelic types − 308 G/A, and has been linked to a variety of inflammatory condition and autoimmune diseases. The − 308 G/A SNP was investigated in AP and interconnected to the TNF level to figure out the responsibilities of TNF-alpha gene polymorphism in the pathogenesis of AP. MethodThe current work design as a case–control study that involves 300 participant divided to 200 patients evaluated as (stable angina n = 100 and unstable angina n = 100) compared with 100 apparently healthy control subjects. The serum level of TNF-alpha was assessed via enzyme-linked immunosorbent assay (ELISA)/sandwich method. The genotype and allele frequency distribution of TNF-alpha rs1800629 gene polymorphism were investigated by TaqMan probe of allelic discrimination method. ResultsThe levels of TNF-alpha were significantly higher in patients with stable and unstable angina pectoris in comparison with controls. The deviation from Hardy–Weinberg equilibrium (HWE) of TNF-alpha genotypes was obvious in control and unstable angina pectoris groups. Moreover, the significant differences between patients with AP and controls under the five genetic models consider the association between TNF-alpha (rs1800629) − 308 G/A and AP with OR > 1. However, data analysis of allelic and genotypic of (rs1800629) − 308 G/A revealed higher significantly differences of GG homozygous and GA heterozygous proportions between stable angina patients and control. The A allele was more represented as etiological allele, and G allele was represented as protective allele. The serum levels of TNF-alpha were significantly higher in subjects with genetically mutated AA genotypes than in subjects with wild GG genotypes in the study groups. ROC curve analysis found the best cutoff value of TNF-alpha level was 77.25 pg/ml. ConclusionAs the results, our data observed a linked of TNF-alpha (rs1800629) − 308 G/A genetic variant with angina pectoris patients, and the A allele has been linked to the production or expression of TNF-alpha serum level and represented an etiological factor of angina pectoris.

ITGA2 Gene Polymorphism Is Associated with Type 2 Diabetes Mellitus in the Kazakhstan Population.

Background and Objectives: Nowadays, every tenth adult in the world suffers from diabetes mellitus (DM). Diabetic retinopathy (DR) is the most common microvascular complication of type 2 DM (T2DM) and a leading cause of acquired blindness in middle-aged individuals in many countries. Previous studies have identified associations of several gene polymorphisms with susceptibility to microvascular complications of DM in various worldwide populations. In our study, we aimed to test the hypothesis of the associations of single nucleotide polymorphisms (SNP) of the VEGF (−2549I/D), RAGE (−429T/C and −374T/A), TCF7L2 (rs7903146), and ITGA2 (BglII) genes with a predisposition to DR among T2DM patients in the Kazakhstan population. Materials and Methods: We conducted a case–control study comparing the genotype distribution and allele frequencies between groups of DR patients (N = 94), diabetic patients without DR (N = 94), and healthy controls (N = 51). Genotypes were identified using the PCR-RFLP method. Results: In all cases, the genotype distribution corresponded to the Hardy–Weinberg equilibrium. The groups of diabetic patients with and without DR did not significantly differ in the genotype distribution of the SNPs studied. Differences between both groups of diabetic patients and healthy controls in four out of five SNPs were also not significant. At the same time, both groups of diabetic patients differed significantly from healthy controls in genotype distribution (p = 0.042 and 0.005, respectively) and allele frequencies (p = 0.021 and 0.002, respectively) of the BglII polymorphism in the ITGA2 gene. After adjusting for multiple comparisons, the differences between the group of diabetic patients without DR and the control group remained significant (pBonf = 0.027 for genotypes and pBonf = 0.009 for alleles). The BglII− allele was associated with diabetes: OR = 1.81 [1.09–2.99] for DR patients, and OR = 2.24 [1.34–3.75] for diabetic patients without DR. The association was also observed in the subset of Kazakhs. Conclusions: This study shows that the BglII polymorphism in the ITGA2 gene can be associated with T2DM but not with DR. According to our data, the risk allele for diabetes is the wild BglII− allele, and not the minor BglII+, which is considered as risky for DR.