Rs1799983 Polymorphism Research Articles

Association of <i>VEGF</i> gene rs699947 and rs2010963 polymorphisms with vascular endothelial growth factor levels in the blood serum of children with lupus nephritis

The growth factor genes VEGF and TGFB1 are involved in the normal functioning of the kidneys, and some polymorphic loci of these genes determine a genetic predisposition to the autoimmune diseases, including systemic lupus erythematosus (SLE) and its dangerous complication, lupus nephritis (LN). The products of these genes, in particular, the vascular endothelial growth factor protein and the transforming growth factor β1 protein are used in clinical practice as markers of endothelial dysfunction for early diagnosis of kidney pathology. However, the relationship between the expression of these proteins and the genotypes/alleles of the polymorphic loci of these genes has not been studied enough, which requires clarification of this issue for the child population of Belarus. In this work, we analyzed the associations of the TGFB1 (rs1800469) and VEGF (rs699947 and rs2010963) gene genotypes with the concentration of their products in the blood serum of patients with LN during exacerbation and remission of the disease. The study did not find a significant relationship between polymorphic variants of the TGFB1 gene (rs1800469) and levels of its product in the blood. An association has been established between the rs699947 and rs2010963 polymorphic variants of the VEGF gene and the serum concentration of the gene product in pediatric patients with LN during exacerbation. It was found that the homozygous minor genotype AA of the polymorphic locus rs699947 and the group of genotypes GC + CC containing at least one minor allele of the locus rs2010963 are associated with higher levels of the gene product in the blood serum of children with LN during disease exacerbation (p < 0.001 and p = 0.036, respectively). Thus, VEGF polymorphic variants associated with an increased concentration of the gene product in the blood serum during disease exacerbation can be considered as markers of the risk of disease exacerbation in patients with LN.

Association of ANRIL Gene Single-Nucleotide Polymorphisms With Allergic Rhinitis in Kurdish Population From Kermanshah, Iran.

Allergic rhinitis (AR) is the most common inflammatory disorder of the upper airway caused by aberrant immune responses to allergens in genetically predisposed individuals. Recently, the long noncoding RNA (lncRNA) antisense noncoding RNA in the INK4 locus (ANRIL) has been identified as a novel genetic factor associated with increased AR risk. This study aimed to evaluate the potential correlation of ANRIL gene single nucleotide polymorphisms (SNPs) with AR risk in the Kurdish population of Kermanshah, Iran. In this case-control study, 130 AR patients and 130 healthy controls were recruited to genotype for two SNPs of the ANRIL gene (rs1333048 and rs10757278) using the Tetra-primer amplification refractory mutation system polymerase chain reaction (T-ARMS-PCR) method. Our results showed no significant difference for the alleles and genotypes frequency distribution of lncRNA ANRIL SNPs (rs1333048 and rs10757278) between AR patients and healthy controls (p > 0.05). Additionally, the dominant, additive and recessive genetic models of both SNPs were not associated with altered susceptibility to AR risk (p > 0.05). The results demonstrated that the ANRIL gene rs1333048 and rs10757278 polymorphisms might not be associated with susceptibility to AR in the Kurdish population of Kermanshah, Iran.

Polymorphism and Association of the E-selectin and ICAM-1-K469E Genes with Sickle Cell Disease in Congo

Introduction: E-selectin and ICAM-1 are cellular adhesion molecules that play important roles in the pathogenesis of Sickle Cell Disease (SCD), especially in the vaso-occlusion process. Numerous studies reported that single nucleotide polymorphisms in E-selectin and ICAM-1 genes may be associated with the clinical expression of several diseases. However, no evidence exists regarding the association with SCD. Objectives: Investigate the association of E-selectins (S128R and S149R) and ICAM-1K469E polymorphisms with SCD in Congolese patients. Methodology: This case-control study included 110 SCD patients in vaso-occlusive pain crisis and 120 controls (healthy non-sickle cell subjects). Polymorphisms were genotyped by PCR-RFLP method. The differences in genotype and allele frequencies between both groups were analyzed with the Fisher’s exact test. A P level of <0.05 was considered significant. Results: The frequency of the ICAM-1-K469E EE genotype was significantly higher in SCD patients compared to controls (8.2% vs 0.8%; P=0.008). The odd ratio value (OR=11.89; 95% CI = 1.48-96.53; P=0.01) indicated a high association with SCD. Furthermore, the E allele was also significantly associated with SCD (OR=1.72; 95% CI=1.10-2.68; P=0.008). By contrast, no statistically significant differences were found between SCD patients and controls regarding the allele and genotype frequencies of E- selectin S128R and S149R polymorphisms. Conclusion: Our findings suggest that the ICAM-1-K469E polymorphism may be associated with SCD among Congolese patients, possibly with the vaso-occlusive crisis. The EE genotype and the E allele may be genetic risk factors. However, because of the small sample size, this report should be considered as exploratory and further studies are required to confirm these genetic associations with SCD.

VEGF gene polymorphisms in Iranian patients with intracranial glioblastoma.

Glioblastoma is one of the most common malignant brain tumors in adults with poor prognosis. Neovascularization is one of the characteristics of these tumors, which is associated with overexpression of vascular endothelial growth factor (VEGF). Accordingly, single nucleotide polymorphisms of this gene could play an important role in structural and functional alterations leading to overexpression of this gene in GBM. A total number of 49 patients with GBM and 50 healthy controls were included in the current study. The Genomic DNA was extracted from brain tumor/tissue samples, and after purification assessment, the alleles, and genotypes of rs3025039 and rs2010963 polymorphisms of the VEGF gene were investigated using T-ARMS-PCR. The "T" allele of rs3025039 was 2.79 times more frequent in GBM patients compared to controls (P=0.01). Moreover, the "CT" genotype was 2.83 times more common among patients (P=0.015), while the "CC" was more frequent in controls (P=0.009). The mean overall survival was significantly different between three genotypes of rs3025039, with the longest survival time in "CT" genotype (15.10±5.21, P=0.041). Besides, rs2010963, was significantly associated with GBM occurrence, with the "G" allele being 1.96 times more frequent in patients (P=0.01), as well as the "GG" genotype, which was 7.87 times more common in patients (P<0.001). Polymorphisms of VEGF could potentially play a role in pathogenesis of GBM, as the allele and genotype distributions of rs3025039 and rs2010963 SNPs were significantly associated with GBM occurrence.

Association Between rs2200733 Polymorphism of PITX2 Gene and the Risk of Atrial Fibrillation.

As observed in recent genetic studies, PITX2 is one of the most popular genes with atrial fibrillation; single nucleotide polymorphism (rs2200733) at chromosome 4q25 (near PITX2) is found to be strongly associated with atrial fibrillation, but it has a difference among Chinese Han population. The basic aim of conducting this study is to find the correlation between PITX2 gene polymorphism and the risk of atrial fibrillation and to identify the possibility for early diagnosis of silent atrial fibrillation and high-risk atrial fibrillation. The study included 98 cases of atrial fibrillation patients and 88 non-atrial fibrillation patients in Affiliated Hospital of Yangzhou University were enrolled in a case-control study. The single nucleotide polymorphism of rs2200733 at 4q25 near PITX2 was genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis. A total of 98 patients with atrial fibrillation were genotyped, and the following frequencies were included in genotype percentages (44.9%, 50%, and 5.1%) while distribution of significant single nucleotide polymorphism rs2200733 consisted (29.55%, 53.41%, and 17.05%) which showed (χ2 = 9.159, P =.01). There was no significant difference in TC genotype frequency (P =.642), frequency of T allele (χ2 = 7.447, P =.006), and T allele was 1.806 times that of the control group (odds ratio = 1.806, 95% CI = 1.179-2.766, P =.006). According to logistic regression analysis, following results were concluded for TC genotype (odds ratio = 3.128, 95% CI = 1.053-9.287, P =.04), or TT genotype (odds ratio = 5.077, 95% CI = 1.653-15.595, P =.005) increased the risk of atrial fibrillation. The genotype and allele frequency distribution of rs2200733 (T/C) near PITX2 is different in the atrial fibrillation group and the control group. The T allele is a risk factor for atrial fibrillation. Compared with the CC genotype, the TT genotype increased the risk of atrial fibrillation.

ПОЛИМОРФИЗМЫ ГЕНОВ NOS3 И CYBA В РАЗВИТИИ ЦИРРОЗА ПЕЧЕНИ У БОЛЬНЫХ ХРОНИЧЕСКИМ ВИРУСНЫМ ГЕПАТИТОМ В В ЯКУТСКОЙ ПОПУЛЯЦИИ

Chronic viral hepatitis B is a significant public health problem. Hepatitis virus carrier factors affect the course of chronic hepatitis B and odds of progression to liver cirrhosis. So, the research for the early development genetic predictors of complications of chronic hepatitis B is relevant. NOS3 and CYBA genes can act as predictor genes for early fibrotic processes in the liver. Researches confirm the role of oxidative stress and the mechanisms of cellular aging in the development of liver fibrosis. The purpose of this study is to identify the relationship between the carriage of polymorphisms of the NOS3 and CYBA genes and the development of liver fibrosis in patients with chronic viral hepatitis B in the Yakut population. Molecular genetic study of SNPs rs1799983 and rs1801131 of the NOS3 gene, rs4673 of the CYBA gene was carried out on 417 people. The collection of representative material was carried out on the basis of the Infectious Diseases Department of the Yakut Republican Clinical Hospital and the NEFU Clinic. As a result of a genetic study, it was found that in carriers of the mutant allele for the rs1799983 polymorphism of the NOS3 gene, the probability of developing liver cirrhosis is 1.81 times higher (0.176–0.098, CI 95%,), in carriers of the rs4673 mutant allele of the CYBA gene, the probability of developing liver cirrhosis is higher by 1.9 times (0.211–0.111, CI 95%), in carriers of the mutant allele for the rs2070744 polymorphism of the NOS3 gene, the probability of developing liver cirrhosis is 2.03 times higher (0.181–0.089, CI 95%). Thus, the obtained results indicate the need for additional studies of these genes, since they can be predictors of the development of liver cirrhosis in patients with chronic viral hepatitis B in the Yakut population.

Diabetic retinopathy progression associated with haplotypes of two VEGFA SNPs rs2010963 and rs699947

ABSTRACT Diabetes-related retinopathy (DR) is one of the sight-threatening diseases. The present case–control study screened 134 patients with type 2 diabetes and 36 healthy ones without diabetes. The genotyping of SNPs rs2010963 and rs699947 of the VEGF gene were done by tetra primers ARMS-PCR. The mutant GG genotype of rs2010963 was significantly associated with DR (OR = 10.29; 95% CI = 2.20–59.06; p = 0.004). No significant associations existed between patients with DR and those with NDR or controls in the genotype or allele frequencies of rs699947 polymorphism. The haplotype analysis for rs2010963 and rs699947 shows the CG haplotype was significantly different between DR and NDR OR 2.0 (95% CI:1.02–3.93), p = 0.043. and between DR and control OR 2.42 (95% CI: 1.2–4.65), p = 0.0108‎. The two SNPs showed moderate Linkage disequilibrium (LD) ‎between DR and control, D’ = 0.64 also, moderate LD between DR cases and NDR, D’ = 0.75. No significant importance for rs699947 SNP with diabetic retinopathy. The 2010963 SNP in the VEGF gene is associated with the risk of NPDR and PDR. The findings also suggest a moderate LD in the two SNPs and their CG haplotype associated with DR progression.

The Association of Biochemical and Genetic Biomarkers in VEGF Pathway with Depression.

VEGF is an important neurotrophic and vascular factor involved in mental disorders. The objective of this study was to verify the effect of genetic polymorphisms in the VEGF pathway on the risk for depression, symptom intensity, and suicide attempts. To examine the association between the VEGF pathway and depression, we genotyped polymorphisms and measured the plasma concentrations of VEGF, KDR, and FLT1 proteins. The participants were 160 patients with depression and 114 healthy controls. The questionnaires that assessed the clinical profile of the patients were the MINI-International Neuropsychiatric Interview, GRID-HAMD21, CTQ, BSI, and the number of suicide attempts. Genotyping of participants was performed using the real-time PCR and protein measurements were performed using the enzyme-linked immunosorbent assay (ELISA). VEGF and its inhibitors were reduced in depression. Individuals with depression and displaying the homozygous AA of the rs699947 polymorphism had higher plasma concentrations of VEGF (p-value = 0.006) and were associated with a greater number of suicide attempts (p-value = 0.041). Individuals with depression that were homozygous for the G allele of the FLT1 polymorphism rs7993418 were associated with lower symptom severity (p-value = 0.040). Our results suggest that VEGF pathway polymorphisms are associated with the number of suicide attempts and the severity of depressive symptoms.

Clusterin is associated with Alzheimer’s disease biomarkers and cognitive scores in the pre‐symptomatic phase of the disease.

AbstractBackgroundClusterin (CLU) is one of the main genetic risk factors of late onset Alzheimer’s disease (AD), and different polymorphisms have been associated with the disease. A GWAS performed in a population isolate from eastern Canada has found the polymorphism rs11136000 of the CLU gene to be associated with increased risk for AD. For the present work, we used two different cohorts (the “at‐risk” pre‐symptomatic PREVENT‐AD and the symptomatic ROSMAP cohort) with the objective of exploring how the rs11136000 polymorphism is associated with clinical manifestations, biomarkers and neuropathology of AD at different disease stages.MethodIn the PREVENT‐AD cohort, ELISAs were used for Tau, phospho(181) Tau (p‐tau), and Aß CSF levels. Cognition was assessed with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Participants were followed for at least 4 years. In the autopsied‐confirmed ROSMAP cohort, Aß load and NFT density in the cortex were measured with immunocytochemistry, and cognition was assessed with the Mini‐Mental State Examination (MMSE). Participants were followed throughout their adult life, until death.ResultIn the cognitively unimpaired PREVENT‐AD cohort, participants who are APOE4 positive and non‐carriers for the rs11136000 T variant had lower CSF Aß1‐42 (p=0.01) and higher CSF p‐tau (p=0.027) (Fig 1). Additionally, participants who are APOE4 positive and have 2 copies of the CLU rs11136000 T variant display significantly higher coding scores (p=0.003), attention scores (p=0.015) and visuospatial/constructional score (p= 0.026) (Fig 2). However, participants who are APOE4 negative and are homozygous for the rs11136000 T variant have lower semantic fluency score (p=0.001), list recall score (p=0.038) and language score (p=0.007) (fig 2). In the ROSMAP cohort, there was no association of the CLU rs11136000 variant with risk of developing dementia, MMSE scores or Braak or CERAD scores.ConclusionOur results confirm the role of the CLU rs11136000 variant in the pathology of AD, particularly in the pre‐symptomatic phase of the disease when pathology begins to unfold.

Investigation of the effect of vascular endothelial growth factor gene 936 C/T polymorphism in familial Mediterranean fever patients

Objectives: This study aims to investigate the effect of vascular endothelial growth factor (VEGF) gene 936C/T polymorphism (rs3025039) on the appearance of phenotypic characteristics of familial Mediterranean fever (FMF) patients that differ with respect to MEditerranean FeVer (MEFV) gene mutations. Here, we investigated a single functional polymorphism in the VEGF gene. Methods: The study group consisted of 223 FMF patients with definite diagnosis according to Tel-Hashomer criteria who carried MEFV gene mutations, while 208 FMF patients with definite diagnosis of FMF but without any mutations, making up the control group, were included in the study. The VEGF gene 936C/T polymorphism was genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Results: Genotype and allele frequencies of the VEGF rs3025039 polymorphism between the two groups were significantly different (p = 0.03 and p = 0.011, respectively). The TT genotype was found to be more frequent in the study group than in controls (4.9% vs. 3.3%, respectively). Conclusions: Our results seem to indicate that the VEGF 936C/T polymorphism affects the appearance of the phenotypic characteristics of FMF. It is possible that other variants of this gene may also have similar effects.

Paraoxonase 1 rs662 polymorphism, its related variables, and COVID-19 intensity: Considering gender and post-COVID complications.

In this study, we aimed to investigate the effect of paraoxonase 1 (PON1) rs662 polymorphism, arylesterase (ARE) activity, and the serum lipid profile in patients with coronavirus disease 2019 (COVID-19) in different stages of the disease considering post-COVID outcomes. A total of 470 COVID-19 patients (235 female and 235 male patients) were recruited into the study, and based on the World Health Organization (WHO) criteria, the patients were divided into three groups: moderate, severe, and critical. PON1 rs662 polymorphism was determined by the Alw 1 enzyme followed by agarose gel electrophoresis. Moreover, serum levels of triglycerides (TG), cholesterol (Chol), high-density lipoprotein-cholesterol (HDL-c), and low-density lipoprotein-cholesterol (LDL-c), as well as the level of the ARE activity of PON1 in the sera of patients were measured at the time of infection and one and three months after hospitalization. There was a significant relationship between the G allele and the severity of the disease. In addition, the probability of death in homozygous individuals (GG) was higher than in heterozygous patients (GA), and it was higher in heterozygous patients than in wild-type individuals (AA). There was also a significant relationship between the decrease in serum lipids and the intensity of COVID-19. On the contrary, at the onset of the disease, the HDL-c level and serum ARE activity were reduced compared to one and three months after COVID-19 infection. The findings of this study indicated the significant impact of PON1 rs662 polymorphism on ARE activity, lipid profiles, disease severity, and mortality in COVID-19 patients.

Association between Common Variants in VEGFA Gene and the Susceptibility of Primary Knee Osteoarthritis.

This study aimed to analyze the relationship between vascular endothelial growth factor A (VEGFA) gene polymorphisms, plasma VEGFA, and the susceptibility of knee osteoarthritis (OA). A total of 404 subjects, 202 knee OA subjects and 202 healthy volunteers, were enrolled into the study. Four distinct polymorphisms of the VEGFA gene were evaluated using polymerase chain reaction-restriction fragment length polymorphism: -2578C/A (rs699947), -1154G/A (rs1570360), -634C/G (rs2010963), and +936C/T (rs3025039). Plasma VEGFA levels were analyzed using enzyme-linked immunosorbent assay. The most common nucleotides in both knee OA subjects and healthy controls were CC for -2578C/A, GG for -1154G/A, CG for -634C/G, and CC for +936C/T in the VEGFA gene. Genotype distribution and allele frequencies of VEGFA -2578C/A, -1154G/A, -634C/G, and +936C/T single nucleotide polymorphisms did not differ between OA patients and the controls. Plasma VEGFA levels showed no difference between OA patients and the controls. In contrast, plasma VEGFA levels of -634C/C genotype were significantly higher in OA patients than in the controls (P = 0.035). According to the -2578A/A genotype, patients with early stage OA had a higher odds ratio than those with advanced stage OA (P = 0.023). VEGFA -2578C/A (rs699947), -1154G/A (rs1570360), -634C/G (rs2010963), and +936C/T (rs3025039) polymorphisms may not be responsible for OA susceptibility in the Thai population. However, the OA patients with A/A genotype at the -2578C/A seemed to have a lower potential risk of developing severe OA than those with the C/A and C/C genotypes. These findings would help elucidate and facilitate a better understanding of the genetic fundamentals of OA.

Association of VEGF cytokine levels and single nucleotide polymorphisms of the &lt;i&gt;VEGF-A&lt;/i&gt; gene with the genital endometriosis in the female population of the Northwestern Federal District of Russia

Aim. To study the association of neoangiogenesis VEGF-A gene polymorphisms C(-460)T (rs833061), C(+936)T (rs3025039) with the risk of genital endometriosis in the population of the Northwestern Federal District; to examine the relationship of polymorphic variants of the VEGF-A neoangiogenesis gene C(-460)T (rs833061), C(+936)T (rs3025039) with the concentration of VEGF-A factor in the blood of females with genital endometriosis.&#x0D; Materials and methods. Eighty-five female volunteers aged from 19 to 44 (mean age 32.9 (5.8) years) with a histologically confirmed diagnosis of genital endometriosis were included in the stud; also, 79 females without endometriosis according to diagnostic laparoscopy for infertility or ectopic pregnancy, aged 20 to 42 (mean age 32.5 (7.2) years, p=0.71) were included in the study. The obtained data were analyzed using SPSS 20.0 statistical software package; 2 value and p value were estimated.&#x0D; Results. In our study, we found an association between the C allele and the CC genotype of the C(+936)T (rs3025039) polymorphism of the VEGF-A gene with genital endometriosis: odds ratio (OR) 2.35, 95% confidence interval (CI) 1.034.61, p=0.023; OR 1.89, 95% CI 1.034.61, p=0.048, respectively. The TT genotype of the C(-460)T (rs833061) polymorphisms and the TT genotype and the C(+936)T (rs3025039) allele of the VEGF-A gene were less common in patients with genital endometriosis: OR 0.43, 95% CI 0.141.29, p=0.023; OR 0.06, 95% CI 0.043.18, p=0.001; OR 0.43, 95% CI 0.231.29, p=0.023 respectively. The blood concentration of VEGF-A cytokine was lower in patients with genital endometriosis at all genotypes of C(-460)T (rs833061) locus of VEGF-A gene than that in females without endometriosis. The analysis of genotype frequency distribution of polymorphic site C(+936)T of the VEGF-A gene showed that the VEGF-A cytokine level was 1.5 times higher in the comparison group with heterozygous ST genotype versus that in homozygous genotypes. Enzyme immunoassay in the examined females showed a 2.5-fold decrease in the level of the VEGF-A angiogenic cytokine in blood serum in patients with endometriosis compared to those without endometriosis.&#x0D; Conclusion. To better understand the pathogenetic features of the endometriosis course and to make an individual prognosis of the course and therapy efficacy, an additional analysis of the associations between the polymorphisms of the listed genes and the angiogenesis factor level is required.

Is Matrix Metalloproteinase-9 Associated with Post-Stroke Cognitive Impairment or Dementia?

Matrix metalloproteinase-9 (MMP-9) is a significant protease required for synaptic plasticity, learning, and memory. Yet, the role of MMP-9 in the occurrence and development of cognitive decline after ischemic stroke is not fully understood. In this study, we used clinical data experiments to further investigate whether MMP-9 and genetic polymorphism are associated with post-stroke cognitive impairment or dementia (PSCID). A total of 148 patients with PSCID confirmed by the Montreal Cognitive Assessment (MoCA) 3 months after onset (PSCID group) were included in the study. The MMP-9 rs3918242 polymorphisms were analyzed using polymerase chain reaction coupled with restriction fragment length polymorphism, and the serum level of MMP-9 was measured using enzyme-linked immunosorbent assay (ELISA). The same manipulations have been done on 169 ischemic stroke patients without cognitive impairment (NCI group) and 150 normal controls (NC group). The expression level of serum MMP-9 in the PSCID group and NCI group was higher compared to the NC group, and the levels in the PSCID group were higher than that in the NCI group (all p < 0.05). Diabetes mellitus, hyperhomocysteinemia, and increased serum MMP-9 levels were the main risk factors of cognitive impairment after ischemic stroke. The serum level of MMP-9 was negatively correlated with the MoCA score, including visual-spatial executive, naming, attention, language, and delayed recall. Genetic polymorphism showed that TC genotype with MMP-9 rs3918242 and CC genotype were associated with a significantly increased risk of PSCID; moreover, the TC genotype significantly increased the risk of cognitive impairment. In the TCCC genotype of MMP-9 rs3918242, diabetes mellitus and hyperhomocysteinemia were associated with the increased risk of PSCID; also, hyperhomocysteinemia could increase the risk of cognitive impairment. MMP-9 level and MMP-9 rs3918242 polymorphism have an important role in the occurrence and development of post-stroke cognitive impairment or dementia (PSCID).

Apolipoprotein A5 gene polymorphism (rs662799) and cardiovascular disease in end-stage kidney disease patients

BackgroundPlasma triglyceride (TG) levels are a significant risk factor for cardiovascular disease (CVD). The APOA5 gene is one of the crucial factors in plasma TG metabolism regulation. The rs662799 polymorphism in the APOA5 gene has been reported to be associated with cardiovascular disease. The goal of this study was to evaluate the potential association of this variant with CVD in patients with end-stage kidney disease. MethodsIn this case–control study the polymorphism was analyzed using the PCR–RFLP method in 800 consecutive patients with ESKD and 500 healthy controls. The genotype and allele distribution was compared between subgroups of patients with CVD (552) versus those without CVD (248).ResultsThe frequency of the minor allele (C) in the healthy individuals was 9% compared to 12% in ESRD group (p = 0.09). The difference between groups was slightly higher for CC homozygote (3.5% versus 1.6%, p = 0.042). The ESKD patient group was analyzed according to the presence or absence of CVD. The significant differences in the polymorphism distribution were revealed in this analysis. The frequency of the C allele in the CVD + subgroup was 14% compared to 6% in CVD- patients (p = 0.001). In the CVD + subgroup the ORs (95% CI) for the C allele and CC genotype were 2.41 (1.61–3.6), p < 0.001 and 3.13 (1.07–9.14), p = 0.036, respectively. This indicates to the association of the variant C allele with cardiovascular disease in ESKD patients. The CC homozygotes have a threefold higher odds of CVD compared to TT homozygotes. The highest frequency of the C allele (18%) was observed in subgroup of patients with diabetic nephropathy, with OR (95% CI) 3.40 (2.13–5.43), p < 0.001.The presence of minor allele (CC and CT genotypes) was significantly associated with increased plasma triglyceride levels (p < 0.001 for both CVD + and CVD- groups).ConclusionThe present study demonstrated the effect of rs662799 polymorphism on plasma TG levels and its association with the development of cardiovascular disease in ESKD patients.

Thalamic gray matter volume mediates the association between KIBRA polymorphism and olfactory function among older adults: a population-based study.

The kidney and brain expressed protein (KIBRA) rs17070145 polymorphism is associated with both structure and activation of the olfactory cortex. However, no studies have thus far examined whether KIBRA can be linked with olfactory function and whether brain structure plays any role in the association. We addressed these questions in a population-based cross-sectional study among rural-dwelling older adults. This study included 1087 participants derived from the Multidomain Interventions to Delay Dementia and Disability in Rural China, who underwent the brain MRI scans in August 2018 to October 2020; of these, 1016 took the 16-item Sniffin' Sticks identification test and 634 (62.40%) were defined with olfactory impairment (OI). Data were analyzed using the voxel-based morphometry analysis and general linear, logistic, and structural equation models. The KIBRA rs17070145 C-allele (CC or CT vs. TT genotype) was significantly associated with greater gray matter volume (GMV) mainly in the bilateral orbitofrontal cortex and left thalamus (P < 0.05) and with the multi-adjusted odds ratio of 0.73 (95% confidence interval 0.56-0.95) for OI. The left thalamic GMV could mediate 8.08% of the KIBRA-olfaction association (P < 0.05). These data suggest that the KIBRA rs17070145 C-allele is associated with a reduced likelihood of OI among older adults, partly mediated through left thalamic GMV.

РОЛЬ ПОЛИМОРФИЗМОВ ГЕНОВ NOS3 И CYBA В ФОРМИРОВАНИИ ОСЛОЖНЕНИЙ ХРОНИЧЕСКОГО ВИРУСНОГО ГЕПАТИТА В Название объекта Название объекта в переводе ФИО автора / список авторов Место работы автора ORCID Ключевые слова Аннотация

In the Republic of Sakha (Yakutia), persistently high incidence rates of CVH remain, as well as mortality rates from complications of liver cirrhosis (LC), as the most common complication. It seems relevant to search for genetic predictors of early development of severe complications in CVH patients in the Yakut population. They can be polymorphic variants of the genes for endothelial dysfunction and oxidative stress NOS3 and CYBA. The collection of representative material was carried out on the basis of the Infectious Diseases Department of the State Budgetary Institution of the Republic of Sakha (Yakutia) of the Yakut Republican Clinical Hospital. In total, 47 DNA samples of patients with chronic viral hepatitis В and liver cirrhosis in its outcome, hospitalized in the Infectious Diseases Department from September 2020 to June 2021, were studied. The control group consisted of patients not infected with viral hepatitis, as well as without pathology of the hemostasis system. The experimental part of the study was carried out by real-time PCR with the melting of hybridization products with a fluorescent label, followed by analysis of the RealBest-Genetics melting curves. As a result of the PCR-RFLP analysis of the rs1799983 polymorphism of the NOS3 gene among patients with chronic viral hepatitis, the T allele frequency was 0.09, and the G allele frequency was 0.91. The frequency of the C allele of the rs2070744 polymorphism of the NOS3 gene was 0.05, the frequency of the T allele was 0.95. The frequency of occurrence of the major allele C of the rs4673 polymorphism of the CYBA gene was 0.78, the minor allele T was 0.22. The relationship between the carriage of polymorphisms of these genes and the disease was not found. However, it was found that carriers of the mutant allele for the rs1799983 polymorphism of the NOS3 gene were 1.81 times more likely to develop liver cirrhosis (95 % CI, odds in the groups 0.176–0.098), carriers of the mutant allele for the rs4673 polymorphism of the CYBA gene were more likely to develop cirrhosis liver cirrhosis is 1.9 times higher (95 % CI, odds in groups 0.211–0.111), in carriers of the mutant allele for the rs2070744 polymorphism of the NOS3 gene, the probability of developing liver cirrhosis is 2.03 times higher (95 % CI, odds in groups 0.181–0.089 ). In carriers of the mutant allele for the rs4673 polymorphism of the CYBA gene, shortening of PT and APTT (17.79 ± 10.26 and 35.13 ± 7.82 sec) is observed, which may indicate a greater tendency of this group to hypercoagulability. In carriers of the mutant allele for the rs2070744 polymorphism of the NOS3 gene, shortening of PT and APTT (11.56 ± 0.99 and 30.12 ± 4.45 sec) is observed, which may also indicate a greater tendency of this group to hypercoagulability.

Relation between endothelial nitric oxide synthase genetic polymorphisms and pulmonary arterial hypertension in newborns with congenital heart disease

ABSTRACT Objective To investigate whether endothelial nitric oxide synthase (eNOS) rs1799983, rs2070744, and rs61722009 gene polymorphisms are associated with pulmonary arterial hypertension (PAH) in South Fujian newborns with congenital heart disease (CHD). Methods Genotyping for the eNOS rs1799983, rs2070744, and rs61722009 polymorphisms was performed using Sanger sequencing in 50 newborns with PAH secondary to CHD [CHD PAH (+)], 52 newborns with CHD without PAH [CHD PAH (-)], and 60 healthy controls. Results The genotype and allele frequency distributions of eNOS rs1799983, rs2070744, and rs61722009 were similar between CHD and healthy controls (P > .05). The frequencies of the eNOS rs1799983 G/T allele were 85% and 15% in the CHD PAH (+) group and 96.15% and 3.85% in the CHD PAH (-) group, the frequency of the T allele was higher in the CHD PAH (+) group than in the CHD PAH (-) group(P< .05), and patients with the GT/TT genotypes of eNOS rs1799983 may present higher PAH (OR = 4.412, 95%CI:1.411–13.797, P= .011). Newborns with the GT/TT genotypes had decreased plasma NO production compared to newborns with the GG genotype (P< .01), and NO levels in the CHD PAH (+) group were significantly lower than those in the CHD PAH (-) group (P < .05). Conclusion The T allele could be a risk factor for PAH in newborns with CHD in South Fujian through decreased levels of nitric oxide production by the endothelium.

Polymorphisms rs2010963 and rs833061 of the VEGF gene in polycystic ovary syndrome.

SUMMARYOBJECTIVE:The polycystic ovary syndrome is the most common endocrine disorder, characterized by the dysregulation of ovarian angiogenesis. This alteration can be related to changes in the activities of the vascular endothelial growth factor (VEGF) gene. Single-nucleotide polymorphisms have been observed in the promoter, intronic, and untranslated regions of the VEGF gene, and several studies have suggested that these polymorphisms may be associated with the risk of polycystic ovary syndrome. This study aimed to investigate the association between rs2010963 and rs833061 polymorphisms and haplotypes of VEGF in the etiology of polycystic ovary syndrome.METHODS:A total of 210 women, 102 diagnosed with polycystic ovary syndrome and 108 controls, participated in this study. The genotyping of the samples was performed by PCR-RFLP and real-time PCR for rs2010963 and rs833061 polymorphisms, respectively. The statistical analyses were performed by the chi-square test and logistic regression model.RESULTS:The clinical characteristics of the patients showed that 75.8% of the patients did not become pregnant, 36.3% had a family history of polycystic ovary syndrome, 58.6% were obese, and about 60% had clinical characteristics of hyperandrogenism. There were no associations between the distribution of rs2010963 (OR 1.24; 95%CI 0.60–2.57; p=0.56) and rs833061 (OR 0.78; 95%CI 0.32–1.92; p=0.59) in patients and controls.CONCLUSIONS:The patients with polycystic ovary syndrome have similar rates of VEGF polymorphisms rs2010963 and rs833061 on the general population.

Association Between Antioxidant Nutrients, Oxidative Stress-Related Gene Polymorphism and Skeletal Fluorosis in Guizhou, China.

BackgroundOxidative stress plays an important role in the pathogenesis of endemic fluorosis. We analyzed associations between oxidative stress-related gene polymorphisms (PON1 rs662, CAT rs769217, rs2300182, and SOD2 rs11968525) and skeletal fluorosis, and examined potential gene–environment interactions with dietary vitamin C, vitamin E, zinc, and selenium intake.MethodsA cross-sectional study was conducted in the Zhijin County, Guizhou Province of China. Skeletal fluorosis was identified according to the Chinese Diagnostic Criteria of Endemic Skeletal Fluorosis. Dietary information was assessed through face-to-face interviews by trained interviewers using a 75-item food frequency questionnaire. The genotype was detected by high throughput TaqMan-MGB RT-PCR technology. Odds ratios (ORs) and 95% CIs were calculated using an unconditional logistic regression model.ResultsIntake of vitamin E, zinc, and selenium was found to be inversely associated with the risk of skeletal fluorosis. The multivariable-adjusted ORs were 0.438 (95% CI: 0.268 to 0.715, P-trend < 0.001) for vitamin E, 0.490 (95% CI: 0.298 to 0.805, P-trend = 0.001) for zinc, and 0.532 (95% CI: 0.324 to 0.873, P-trend = 0.010) for selenium when comparing the highest with the lowest quartile. The relationship for vitamin C was not observed after adjustment for risk factors. Furthermore, participants with PON1 rs662 AA genotype had a significantly decreased risk of skeletal fluorosis compared with those with the GG genotype (OR = 0.438, 95% CI: 0.231 to 0.830). GG + AG genotype carriers were 2.212 times more likely to have skeletal fluorosis than AA carriers (OR = 2.212, 95% CI: 1.197 to 4.090). Compared with AA carriers, AG carriers had a 2.182 times higher risk of skeletal fluorosis (OR = 2.182, 95% CI: 1.143 to 4.163). Although we observed the risk of skeletal fluorosis was higher with a lower intake of antioxidant nutrients, the potential interactions between nutrient intake and genetic polymorphisms were not observed.ConclusionParticipants with a higher intake of vitamin E, zinc, and selenium have a lower likelihood of skeletal fluorosis. In addition, the PON1 rs662 polymorphism is related to skeletal fluorosis.