Rs1799983 Polymorphism Research Articles

The relationship between polymorphic variants of the endothelial NO-synthase gene and the course of diabetic nephropathy in patients with type 2 diabetes mellitus

Objective — to identify a possible association between the endothelial nitric oxide synthase (eNOS) gene G894T (rs1799983) polymorphism and the markers of renal function and glucose metabolism in patients with type 2 diabetes mellitus (DM2) with diabetic nephropathy (DN).
 Materials and methods. Examinations 126 patients with diabetic nephropathy (DN). The control group included 20 healthy individuals. Patients with DM2 were divided into two groups depending on the eNOS rs1799983 gene polymorphism: group I — patients with DN and G/G genotype eNOS G894T gene (n=80); group II — patients with DN and G/T and T/T genotypes eNOS G894T gene (n=46). Genotyping of the of the eNOS rs1799983 gene polymorphism was performed by the Taq‑Man® Fast Universal PCR Master Mix (Applied Biosystems, USA) and TaqMan® SNP Assay (Applied Biosystems, USA).
 Results. It has been established that in patients with DN, the distribution of genotypes of the G894T polymorphism of the eNOS gene corresponded to the Hardy‑Weinberg equilibrium in all groups and does not differ significantly from European populations. In diabetic patients with DN the 3 times higher total frequency of G/T and T/T genotypes eNOS G894T gene was established when compared to the control group. These findings prove the undoubted influence of the T allele on the development of DN in this group of patients. DN patients with genotypes G/T and T/T had significantly higher blood glucose and HOMA index (p <0.05) than G homozygotes (genotype G/G). Patients with DN and G/G genotype eNOS G894T gene had better glomerular filtration rate and lower albuminuria compared to patients with G/T and T/T genotypes (p <0.05).
 Conclusions. The establishing of association of eNOS gene polymorphism with the disease and further assessment of individual genetic risk is important for the development of a differentiated approach to the prevention and treatment of DN in patients with DM2 depending on the hereditary predisposition of an individual patient. Therefore, currently one of the most progressive approaches is to develop a strategy for early diagnosis, prognosis and preventive therapy of the disease using genetic markers.

Association of the polymorphisms of the cholesteryl ester transfer protein gene with coronary artery disease: a meta-analysis.

This meta-analysis aimed to assess the association of the polymorphisms of cholesterol ester transfer protein (CETP) rs708272 (G>A), rs5882 (G>A), rs1800775 (C>A), rs4783961 (G>A), rs247616 (C>T), rs5883 (C>T), rs1800776 (C>A), and rs1532624 (C>A) with coronary artery disease (CAD) and the related underlying mechanisms. A comprehensive search was performed using five databases such as PubMed, EMBASE, Web of Science, Cochrane Library and Scopus to obtain the appropriate articles. The quality of the included studies was assessed by the Newcastle-Ottawa Scale. The statistical analysis of the data was performed using STATA 17.0 software. The association between CETP gene polymorphisms and risk of CAD was estimated using the pooled odds ratio (OR) and 95% confidence interval (95% CI). The association of CETP gene polymorphisms with lipids and with CETP levels was assessed using the pooled standardized mean difference and corresponding 95% CI. P < 0.05 was considered statistically significant. A total of 70 case-control studies with 30,619 cases and 31,836 controls from 46 articles were included. The results showed the CETP rs708272 polymorphism was significantly associated with a reduced risk of CAD under the allele model (OR = 0.846, P < 0.001), the dominant model (OR = 0.838, P < 0.001) and the recessive model (OR = 0.758, P < 0.001). AA genotype and GA genotype corresponded to higher high-density lipoprotein cholesterol (HDL-C) concentrations in the blood compared with GG genotype across the studied groups (all P < 0.05). The CETP rs5882 and rs1800775 polymorphisms were not significantly associated with CAD under the allele model (P = 0.802, P = 0.392), the dominant model (P = 0.556, P = 0.183) and the recessive model (P = 0.429, P = 0.551). Similarly, the other mentioned gene polymorphisms were not significantly associated with CAD under the three genetic models. The CETP rs708272 polymorphism shows a significant association with CAD, and the carriers of the allele A are associated with a lower risk of CAD and higher HDL-C concentrations in the blood compared to the non-carriers. The CETP rs5882, rs1800775, rs4783961, rs247616, rs5883, rs1800776, and rs1532624 are not significantly associated with CAD. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023432865, identifier: CRD42023432865.

Application of PCR-RFLP technique for determining the VEGFA rs3025039 (+936C&gt;T) polymorphism

Background: The VEGFA gene encodes vascular endothelial growth factor A (VEGF-A), which plays a key role in vasculogenesis and angiogenesis. The VEGFA rs3025039 (+936C&gt;T) polymorphism is associated with many diseases. This study aimed to: (1) Apply PCR-RFLP technique to identify the VEGFA rs3025039 (+936C&gt;T) polymorphism; (2) Primarily evaluate the distribution of genotypes and allele frequencies of the rs3025039 polymorphism in volunteers. Materials and methods: DNA extraction was isolated from peripheral blood of 60 volunteers. Determining the VEGFA rs3025039 (+936C&gt;T) polymorphism by PCR-RFLP technique. Confirming the results of the genotypes randomly by Sanger sequencing. Results: All PCR-RFLP results of validated samples were in concordance with sequencing results. The distribution of CC, CT and TT genotypes by rs3025039 polymorphism accounted for 80%, 16.7% and 3.3%, respectively. The frequencies of C and T alleles were 88.3% and 11.7%, respectively. Conclusion: Successfully applying PCR-RFLP technique to determine the VEGFA rs3025039 (+936C&gt;T) polymorphism, which establishes the groundwork for further research into the association between this polymorphism and various disorders. Key words: VEGFA, rs3025039, PCR-RFLP.

Serum Arylesterase, Paraoxonase, and Lactonase Activities and Paraoxonase-1 Concentrations in Morbidly Obese Patients and Their Relationship with Non-Alcoholic Steatohepatitis.

Paraoxonase-1 (PON1) is an antioxidant enzyme associated with high-density lipoproteins (HDL). Reduced serum PON1 activity is found in diseases marked by oxidative stress and inflammation, but its role in obesity remains unclear. This study investigated PON1 activities and concentrations in morbidly obese individuals and explored the impacts of the genetic polymorphism PON1 rs662 and non-alcoholic fatty liver disease on enzymatic properties. We recruited 1349 morbidly obese patients undergoing bariatric surgery and 823 non-obese volunteers. PON1-related variables, including arylesterase, paraoxonase, and lactonase activities and PON1 concentrations, were examined. Our results showed that morbidly obese individuals exhibited higher PON1 concentrations but lower enzymatic activities than non-obese individuals. We observed inverse associations of arylesterase and paraoxonase activities with waist circumference (rho = -0.24, p < 0.001, and rho = -0.30, p < 0.001, respectively) and body mass index (rho = -0.15, p = 0.001, and rho = -0.23, p < 0.001), as well as direct associations of arylesterase, paraoxonase, and lactonase activities with HDL cholesterol (rho = 0.11, p = 0.005, rho = 0.20, p < 0.001, and rho = 0.20, p < 0.001). No significant differences were observed regarding metabolic syndrome, type 2 diabetes mellitus, hypertension, dyslipidemia, rs662 polymorphism allele frequencies, or the diagnosis of non-alcoholic steatohepatitis. Nevertheless, correlations were found between certain PON1-related variables, steatosis, and ballooning. In conclusion, changes in PON1-related variables in morbidly obese patients are dependent on the disease itself and HDL levels. The relationships between these variables and specific liver histological changes raise intriguing questions for consideration in future studies.

Association of a Genetic Variant in Chromosome 9p21 with Increased Risk of Developing Cervical Cancer

Background: Cervical cancer is one of the most prevalent gynecologic cancers associated with high morbidity and mortality worldwide. There is mounting evidence indicating an association between the 9p21 locus genetic variants with susceptibility to various human malignancies. In this current study, we aimed to evaluate the potential relationship between the rs1333049 genetic variant in chromosome 9p21 and the risk of cervical carcinogenesis. Methods: The possible correlation between rs1333049 polymorphism and susceptibility to cervical cancer was investigated in 221 patients with or without cancer. DNAs were isolated and genotyped using a TaqMan-based real-time RT-PCR method. Results: The rs1333049 genetic variant was found to be correlated with an elevated risk of cervical neoplasia using recessive and additive genetic models (p &lt; 0.001). Conclusion: Our findings indicated that the CDKN2A/B genetic variant (rs1333049) was significantly associated with an elevated risk of cancer, suggesting its potential as a novel predictive marker for cervical carcinogenesis.

CDKN2B-AS (rs2891168), SOD2 (rs4880), and PON1 (rs662) polymorphisms and susceptibility to coronary artery disease and type 2 diabetes mellitus in Iranian patients: A case-control study.

Coronary artery disease (CAD) is a devastating illness and primary cause of death worldwide that arises from a combination of genetic and environmental factors. Several large-scale studies found that 9p21.3, superoxide dismutase 2 (SOD2), and paraoxonase 1 (PON1) polymorphisms increase type 2 diabetes mellitus (T2DM) and/or coronary artery disease (CAD) risk. Our research aimed to investigate whether the SNPs of the 9p21.3 locus (rs28911698), SOD2 (rs4880), and PON1 (rs662) genes were associated with the risk of T2DM and/or CAD in the Iranian population. In this case-control study four group subjects including patients with CAD non-T2DM, with CAD and T2DM, non-CAD with T2DM, and non-CAD non-T2DM were recruited to the study from 2019 to 2020. Molecular analysis was carried out by allele specific-polymerase chain reaction (AS-PCR) technique for rs4880, Taqman genotyping assay for rs2891168, and PCR followed by restriction fragment length polymorphism (PCR-RFLP) technique for rs662. The rs2891168 polymorphism presented an elevated risk of CAD in non-T2DM with CAD and with T2DM CAD groups compared to the non-T2DM non-CAD group with GG genotype and dominant model after adjustment (p < 0.05). G-allele in PON1 rs662 polymorphism associated with increased risk of T2DM in T2DM non-CAD, and T2DM CAD groups compared to non-T2DM non-CAD group with dominant model, GG and AG genotypes (p < 0.05). However, SOD2 rs4880 polymorphism presented no significant association with the development of diabetes or CAD. These results provide a prime witness that rs2891168 and rs662 gene variants might have a possible increased risk of CAD and T2DM occurrence, respectively. To obtain more definitive and accurate results in this area, further research is required.

KIBRA single nucleotide polymorphism is associated with hippocampal subfield volumes and cognition across development.

The hippocampus (Hc) consists of cytoarchitectonically and functionally distinct subfields: dentate gyrus (DG), cornu ammonis (CA1-3), and subiculum. In adults, a single nucleotide polymorphism (rs17070145, C→ T) in KIBRA, a gene encoding the eponymous (KIdney-BRAin) protein, is associated with variability in Hc subfield volumes and episodic memory. T-allele carriers have larger DG and CA volumes and better episodic memory compared to C-homozygotes. Little is known, however, about KIBRA's role in the development of the brain and cognition. In a sample of children, adolescents, and young adults (N = 176, ages 5- 25years), we replicated the adult association between KIBRA T-allele and larger DG and CA volumes but observed no relationship between KIBRA rs17070145 polymorphism and episodic memory. We noted, however, that a general cognitive performance index (IQ) differed across the allelic groups, with the lowest scores among T-homozygotes and the highest among C-homozygotes. Thus, in this developmental sample, KIBRA appears to have opposing effects on regional brain volume and cognition. These influences of KIBRA SNP may stem from associations between developmental reduction in brain volume and gains in cognitive performance-a hypothesis to be tested in longitudinal studies.

Lack of association between the VEGFA gene polymorphisms and preterm birth in Korean women.

Preterm birth (PTB), a pregnancy-related disease, is defined as a birth before 37 weeks of gestation. It is a major cause of maternal mortality and morbidity worldwide, and its incidence rate is steadily increasing. Various genetic factors can contribute to the etiology of PTB. Vascular endothelial growth factor A (VEGFA) gene is an important angiogenic gene and its polymorphisms have been reported to be associated with PTB development. Therefore, we conducted a case-control study to evaluate the association between VEGFA rs699947, rs2010963, and rs3025039 polymorphisms and PTB in Korean women. A total of 271 subjects (116 patients with PTB and 155 women at ≥38 weeks of gestation) were analyzed in this study. The genotyping of VEGFA gene polymorphisms was performed using polymerase chain reaction- restriction fragment length polymorphism. No significant association between the patients with PTB and the control groups was confirmed. In the combination analysis, we found a significant association between PTB and VEGFA rs699947 CC-rs2010963 GG-rs3025039 CC combination (odds ratio, 3.77; 95% confidence interval, 1.091 to 13.032; p = 0.031). The VEGFA rs699947, rs2010963, and rs3025039 polymorphisms might have no genetic association with the pathogenesis of PTB in Korean women. However, the combination analysis indicates the possibility that VEGFA acts in PTB pathophysiology. Therefore, larger sample sets and replication studies are required to further elucidate our findings.

Lack of Association between CD33 rs3865444 and Amyotrophic Lateral Sclerosis: A Case-Control Study.

Microglial activation is considered to assume a role in the pathogenesis of Amyotrophic Lateral Sclerosis (ALS). To date, the relationship between ALS and the rs3865444 polymorphism of the cluster of differentiation 33 (CD33) has not been explored. The current report aimed to investigate the potential connection between CD33 rs3865444 and ALS. Patients diagnosed with sporadic ALS according to the revised El Escorial criteria, as well as age and sex matched community controls, were enrolled. Two evenly numbered, age and sex matched groups of 155 participants each were genotyped. No association was found between rs3865444 and ALS [log-additive odds ratio (OR) = 0.83 (0.57, 1.22), over-dominant OR = 0.86 (0.55, 1.36), recessive OR = 0.73 (0.25, 2.17), dominant OR = 0.82 (0.52, 1.29), co-dominant OR1 = 0.68 (0.23, 2.05) and co-dominant OR2 = 0.84 (0.53, 1.33)]. Moreover, no relationship was established between rs3865444 and the age of ALS onset based on both unadjusted and sex adjusted Cox-proportional hazards models. Finally, no association between rs3865444 and ALS was found in subgroup analyses based on the site of ALS onset (bulbar or spinal) and sex. The current analysis is the first to report that rs3865444 is not linked to ALS. Larger multi-racial studies are required to confirm these findings.

MMP9 −1562 C/T POLİMORFİZMİ, TÜRK TİP 2 DİABETES MELLİTUS HASTALARINDA ARTMIŞ DİYABETİK RETİNOPATİ RİSKİ İLE İLİŞKİLİDİR

Objective&#x0D; Type 2 diabetes mellitus (T2DM) and diabetic&#x0D; retinopathy (DR) development is affected by genetic&#x0D; factors. Matrix metalloproteinases (MMPs) are involved&#x0D; in many cellular processes, such as remodeling of&#x0D; extracellular matrix proteins and angiogenesis. In&#x0D; this study, we investigated the relationship between&#x0D; MMP9 −1562 C/T (rs3918242) polymorphism and the&#x0D; development of T2DM and DR in Turkish population.&#x0D; Material and Method&#x0D; A total of 510 participants, involving 168 T2DM&#x0D; cases with DR, 168 T2DM cases without DR,&#x0D; and 174 controls, were included in the study. The&#x0D; polymerase chain reaction-restriction fragment length&#x0D; polymorphism (PCR-RFLP) method was carried out&#x0D; to identify genotypes.&#x0D; Results&#x0D; The CT, CT+TT genotypes and the T allele of the&#x0D; MMP9 −1562 C/T polymorphism were associated with&#x0D; increased risk of DR (p=0.001). On the other hand,&#x0D; no relationship was found between the development&#x0D; of T2DM and this polymorphism. In addition,&#x0D; CT (p=0.010) and CT+TT (p=0.015) genotype&#x0D; frequencies were found to be higher in proliferative&#x0D; diabetic retinopathy (PDR) cases compared to nonproliferative&#x0D; diabetic retinopathy (NPDR) cases, but&#x0D; after regression analysis, only insulin use (p=0.003)&#x0D; was found to be associated with the development of&#x0D; PDR.&#x0D; Conclusion&#x0D; Our data show that the MMP9 −1562 C/T polymorphism&#x0D; is associated with the development of DR in Turkish&#x0D; T2DM patients, but no significant relationship was&#x0D; found between this polymorphism and the severity of&#x0D; DR and the development of T2DM.

ENOS polymorphisms on male infertility: An updated systematic review and meta-analysis.

This meta-analysis was performed to examine the association of 3 endothelial nitric oxide synthase (eNOS) gene polymorphisms with male infertility. The literature on the relation between the mutant of eNOS and male infertility before July 1, 2022, was conducted in Pubmed, Medline, and Web of Science. The search strategy is as follows: (eNOS OR ECNOS OR nitric oxide synthase 3 OR NOS3) AND (polymorphism OR mutation OR variation OR SNP OR genotype) AND (male infertility). Statistical analysis was performed with the web of MetaGenyo, Stata 12, trial sequential analysis 0.9Beta, and the web of GTEx. Overall, 13 studies (26 case-controls) were included involving 6518 cases and 5461 controls for 3 polymorphisms (rs2070744, rs1799983, rs61722009) of eNOS. We found that eNOS rs2070744 was correlated with an increased risk of male infertility (C vs. T: odds ratio [OR], 1.48; 95% confidence interval [CI], [1.19-1.85]; CC vs. TT: OR, 2.59; 95% CI, [1.40-4.80]; CT vs. TT: OR, 1.17; 95% CI, [1.00-1.38]; CC vs. CT + TT: OR, 2.50; 95% CI, [1.35-4.62]; CC + CT vs. TT: OR, 1.41; 95% CI, [1.21-1.64]). And eNOS rs1799983 was correlated with an increased risk of male infertility (allele contrast T vs. G: OR, 1.41; 95% CI, [1.01-1.96]; P = .043; recessive model TT vs. TG + GG: OR, 2.00; 95% CI, [1.03-3.90]; P = .042). In the stratified analysis of rs61722009, we found Asians might be correlated with an increased risk of male infertility (4a vs. 4b: OR, 1.50; 95% CI, [0.94-2.38]; 4a4a vs. 4b4b: OR, 2.56; 95% CI, [0.70-9.38]; 4a4b vs. 4b4b: OR, 1.36; 95% CI, [0.87-2.13]; 4a4a vs. 4a4b + 4b4b: OR, 2.57; 95% CI, [0.91-7.30]; 4a4a + 4a4b vs. 4b4b: OR, 1.44; 95% CI, [0.87-2.40]). The eNOS rs2070744 polymorphism and rs1799983 are associated with the risk of male infertility, and rs61722009 might be a risk factor for Asians.

Elevated Matrix Metalloproteinase 9 in Treatment Resistant Bipolar Depression

Objective: Matrix metalloproteinase is a family of proteases with different pathophysiological roles. Matrix metalloproteinase 9 (MMP9) plays an enzymatic role in the restructuring of the extracellular matrix and adhesion molecules. MMP9 is upregulated in pro-inflammatory states and leads to breakdown of tight junctions thereby increasing blood-brain barrier (BBB) permeability. MMP9 may contribute to the pathophysiology of bipolar disorder (BD) via proteolysis of the BBB thus allowing entry of cytokines and neurotoxic agents into CNS. Polymorphisms of the MMP9 gene may pose increased risk for BD and schizophrenia. In this study we sought to determine MMP9 levels in treatment resistant bipolar depressed patients before and after treatment.&#x0D; Methods: Treatment resistant bipolar depressed patients were treated with escitalopram, in combination with the COX-2 inhibitor, celecoxib. It was hypothesized that combination treatment would reverse resistance and augmented treatment responses. This was a 10-week, randomized, double-blind, two-arm, placebo-controlled study.&#x0D; Results: MMP9 levels were higher in bipolar depressed patients compared to healthy controls at baseline, however, the difference did not reach significance. Levels decreased after treatment reaching significance in the escitalopram plus placebo group. Female patients had significantly lower MMP9 levels at end of treatment. MMP9 was higher in carriers the MMP9 SNP, rs3918242, than in noncarriers, but the difference did not reach statistical significance.&#x0D; Conclusion: MMP9 decreased in bipolar depressed patients with treatment. Age, sex and the rs3918242 polymorphism play a role in MMP9 levels. Future studies should confirm the role of MMP9 in the pathogenesis and pathophysiology of bipolar disorder, as a potential diagnostic biomarker.

Association of AGT (T704C) and NOS3 (G894T) Gene Polymorphisms with Treatment-Resistant Hypertension in the Uzbek Population

The aim of our study was to assess the effect of polymorphic markers of the AGT T704C (M235T) rs699 and NOS3 G894T (Glu298Asp) rs1799983 SNPs on the risk of the development of treatment-resistant hypertension (TRH). Methods and Results: The study included 178 patients (mean age of 56.67±11.12 years) with AH Grades 1-3 (ESC/ESH, 2018), who were on outpatient treatment at the Republican Specialized Scientific and Practical Medical Center for Cardiology. Genomic DNA samples were isolated from the peripheral blood leukocytes by using the DiatomТМ DNA Prep 200 Kit (Isogen Laboratory LLC, Moscow, Russia) according to manufacturer`s protocol. A multiplex RT-PCR assay was used to detect the AGT T704C (M235T) rs699 SNP and NOS3 G894T (Glu298Asp) rs1799983 SNP. We studied the distribution of the AGT T704C (M235T) rs699 polymorphism in 61 Uzbek patients with TRH (cases) and 117 Uzbek patients with non-TRH (controls) (Group 1) and the distribution of the NOS3 G894T (Glu298Asp) rs1799983 polymorphism in 61 Uzbek patients with TRH (cases) and 115 Uzbek patients with non-TRH (controls) (Group 2). Our results indicate a significantly greater accumulation of the C allele and CC genotype of the AGT T704C (M235T) rs699 SNP among TRH patients than among patients with non-TRH. We found a significant association between the AGT T704C (M235T) rs699 SNP and the risk of TRH under the multiplicative genetic model (C vs. T : OR=1.85, 95% CI: 1.17-2.92, P=0.006), additive model (CC vs.TT vs. TC; OR=3.00, 95% CI: 1.56-5.75, P=0.009), and recessive model (CC vs. TC+TT; OR=3.00, 95% CI: 1.56-5.75, P=0.0008). For the NOS3 G894T (Glu298Asp) rs1799983 SNP, the multiplicative model showed a significant risk of TRH with the carriage of the T allele (OR=1.99, 95% CI: 1.20-3.28, P=0.007), and the additive model showed a significant risk of TRH with the carriage of the heterozygous GT genotype (OR=2.25, 95% CI: 1.17-4.33, P=0.01). At the same time, the carriage of the G allele (OR=0.5, 95% CI: 0.30-0.83, P=0.007) and GG genotype (OR=0.40, 95% CI: 0.21-0.76, P=0.01) may be protective against the development of TRH. Conclusion: Further genetic studies of TRH may help achieve better individual outcomes by optimizing drug therapy based on genetic variation.

EVALUATING THE ASSOCIATION BETWEEN APOLIPOPROTEIN A5 SINGLE NUCLEOTIDE POLYMORPHISMS (APOA5 SNPS) AND HYPERTRIGLYCERIDEMIA

The retrospective study was conducted at the Faisalabad Institute of Cardiology from January 2022 to January 2023 to evaluate the association between apolipoprotein A5 single nucleotide polymorphisms (APOA5 SNPS) and hypertriglyceridemia in the Pakistani population and assess the efficacy of fibrate therapy in hypertriglyceridemic patients. Blood samples of patients were collected for DNA extraction by the standard inorganic method. Extracted DNA was analyzed biochemically and genetically following the selection and genotyping of the APOA5 gene to know SNP variants with risk alleles. We analyzed lipid profiles, including TG (triglyceride), HDL (high-density lipoprotein), and LDL (low-density lipoprotein) levels of hypertriglyceridemic patients, then compared them to normal and fibrate-treated individuals. We compared APOA5 (rs662799) SNP (single nucleotide polymorphism) among 50 hypertriglyceridemic, 50 healthy controls, and among the same 50 hypertriglyceridemic patients who were given fibrate. Results showed that fibrate decreased TG level and LDL by about 30-45% and 20-25%, respectively; increased high-density lipoprotein by 10-15% and total cholesterol decreased by 6-8% in Pakistani. Hypertriglyceridemia risk was significantly increased by a minor allele of APOA5 rs662799 polymorphism. Minor allele carriers of rs662799 had an odd ratio of (95% CI) 1.5 (1.03-2.18) (P = 0.032). Risk allele frequency differed among hypertriglyceridemic patients, healthy controls, and fibrate-treated hypertriglyceridemic individuals. We analyzed that 87.5% of healthy controls exhibited no risk allele, while 78% did not show this risk allele among hypertriglyceridemic patients. It was concluded that APOA5 rs662799 polymorphism is a genetic determinant of hypertriglyceridemia. Fibrate caused a reduction in TG and LDL and caused an elevation of HDL-C among hypertriglyceridemic patients.

Vitamin E intake and paraoxonase 1 (PON1) rs662 genetic polymorphism are associated with colorectal cancer risk in a Korean population

Vitamin E and paraoxonase 1 (PON1) are associated with cancer development. However, their interactive effect on colorectal cancer (CRC) risk is inconclusive. We conducted a case–control study including 1,351 CRC patients and 2,670 controls at the Korean National Cancer Centre (KNCC). There was an inverse association between vitamin E intake and CRC risk (odds ratio (OR) = 0.31; 95% confidence interval (CI) = 0.22–0.42). We identified a reduced CRC risk among individuals with CC genotype of PON1 rs662 polymorphism compared with subjects carrying the T allele (OR = 0.74; 95% CI = 0.61–0.90). The highest interaction between vitamin E intake and PON1 rs662 variants was significant for the subjects carrying the CC genotype (p-interaction = 0.014). This study provided further supporting evidence that vitamin E intake is associated with lower odds of CRC. Furthermore, the activity of vitamin E is strengthened among individuals carrying C allele of the PON1 rs662 polymorphism.

Association between the Polymorphisms rs2070744, 4b/a and rs1799983 of the NOS3 Gene with Chronic Kidney Disease of Uncertain or Non-Traditional Etiology in Mexican Patients.

Background and Objectives: Chronic Kidney Disease of uncertain or non-traditional etiology (CKDnT) is a form of chronic kidney disease of undetermined etiology (CKDu) and is not associated with traditional risk factors. The aim of this study was to investigate the association of polymorphisms rs2070744, 4b/a and rs1799983 of the NOS3 gene with CKDnT in Mexican patients. Materials and Methods: We included 105 patients with CKDnT and 90 controls. Genotyping was performed by PCR-RFLP's, genotypic and allelic frequencies were determined and compared between the two groups using χ2 analysis, and differences were expressed as odd ratios with 95% confidence intervals (CI). Values of p < 0.05 were considered statistically significant. Results: Overall, 80% of patients were male. The rs1799983 polymorphism in NOS3 was found to be associated with CKDnT in the Mexican population (p = 0.006) (OR = 0.397; 95% CI, 0.192-0.817) under a dominant model. The genotype frequency was significantly different between the CKDnT and control groups (χ2 = 8.298, p = 0.016). Conclusions: The results of this study indicate that there is an association between the rs2070744 polymorphism and CKDnT in the Mexican population. This polymorphism can play an important role in the pathophysiology of CKDnT whenever there is previous endothelial dysfunction.

POLYMORPHISM OF GENES RESPONSIBLE FOR NEUROHUMORAL MECHANISMS OF DEVELOPMENT OF CHRONIC HEART FAILURE WITH PRESERVED EJECTION FRACTION IN PERSONS WITH TYPE 2 DIABETES MELLITUS

The search for genetic markers of chronic heart failure (CHF), comorbid with type II diabetes mellitus, is an urgent task. The study aim was to identify genetic polymorphisms associated with impaired neurohumoral regulation in patients with CHF with preserved and low ejection fraction and type II diabetes mellitus. Material and methods. Polymorphisms of genes responsible for neurohumoral mechanisms of CHF development were studied in 167 patients (69.9±10.1 years) with type II diabetes mellitus, hypertension, CHF with preserved or low ejection fraction, and healthy volunteers. Results and discussion. The angiotensin gene, angiotensin-converting enzyme, angiotensin 1 and 2 receptors polymorphisms are not involved in the CHF formation in patients with type II diabetes mellitus. In the control group, rs1403543 GA polymorphism was found in 90.48% of the examined, in patients with CHF with preserved ejection fraction and type II diabetes mellitus, GA and AA variants were found in 20% of cases, in the CHF group with a low ejection fraction AA polymorphism was found in 53.85% of the examined. It is possible they do not participate in the formation of CHF in patients with type II diabetes mellitus, or have a protective effect. The gene GNB: 825 C &gt; T rs5443 polymorphism was detected from 53.33 to 61.9% of the examined in all groups. rs1799998 polymorphism is not associated with the development of CHF. The rs2070744 polymorphism is associated with the development of CHF with a preserved ejection fraction, but not CHF with a low ejection fraction, in patients with type II diabetes mellitus. The gene NOS3: 894 G &gt; T rs1799983 in heterozygous and homozygous variants polymorphism was more common in patients with CHF with preserved ejection fraction (statistically insignificant). Conclusions. CHF with a preserved ejection fraction and CHF with a low ejection fraction in patients with type II diabetes mellitus are associated with different polymorphisms and have different pathogenesis. The gene AGTR2 polymorphism rs1403543 in patients with type II diabetes mellitus and CHF with preserved ejection fraction occurs less frequently than in the control group. The gene GNB polymorphism rs5443 in patients with CHF with a preserved ejection fraction and CHF with a low ejection fraction occurs much less frequently than in the control group. The gene NOS3 polymorphism rs2070744 in patients with CHF with a preserved ejection fraction occurs significantly more often than in the control group and in patients with CHF with a low ejection fraction.

Endothelial nitric oxide synthase rs1799983 gene polymorphism is associated with the risk of developing intracranial aneurysm.

The intracranial aneurysm (IA) rupture is associated with a subarachnoid hemorrhage. One third of patients die, and one third remain depend for daily activities. Genetic factors are crucial in the formation and clinical evolution of IAs. Multiple loci have been associated with AIs, much of them implicating multiple pathways related to vascular endothelial maintenance and extracellular matrix integrity. Thus, the aim of our study was to characterize whether polymorphisms in genes implicated in the vascular endothelial maintenance could modify the risk of developing IAs. We have studied 176 patients with IA recruited in the Service of Neurosurgery at the University Hospital of Valladolid (Spain) and a control group if 150 sex-matched healthy subjects. Clinical variables were collected from each patient. We have analyzed VEGFA rs833061, VEGFR2 rs2071559, endothelin rs5370, endoglin rs3739817, and eNOS rs1799983 polymorphisms. Our results showed that allele T of the eNOS rs1799983 polymorphism is correlated with decreased risk of developing the disease; thus, allele G of the eNOS rs1799983 polymorphism increased the risk of developing IA. The association of eNOS rs1799983 polymorphism with the risk to suffer IA reinforces the hypothesis that genetic variants in eNOS gene could be crucial in the pathogenesis of IA.

Association between ANRIL polymorphisms and risk of obsessive-compulsive disorder

Obsessive-compulsive disorder (OCD) is a disorder in which genetic factors participate. ANRIL is an example of long non-coding RNAs with crucial roles in the pathoetiology of multifactorial disorders, including neuropsychiatric conditions. We appraised association between rs1333045, rs1333048, rs10757278 and rs4977574 polymorphisms and OCD in Iranian population. There were no remarkable differences in allele and genotype distribution of rs1333045, rs1333048, rs4977574, and rs10757278 between OCD Patients and normal controls. However, the CCGG haplotype (equivalent to rs1333045, rs1333048, rs4977574 and rs10757278, respectively) has been shown to decrease risk of OCD (OR (95% CI) = 0.57 (0.39–0.85), P value-0.006 and FDR q-value = 0.041). On the other hand, TCGA haplotype has been found as a risk haplotype for OCD (OR (95% CI) = 5.17 (1.44–18.55), P value = 0.005 and FDR q-value = 0.041). In brief, the current study indicates association between two ANRIL haplotypes and risk of OCD in Iranian people.

Genetic association analysis of rs662799 ( − 1131A > G) polymorphism of APOA5 gene with morphometric and physio-metric traits using multiplex PCR

BackgroundThe apolipoprotein A5 (APOA5) gene, significantly expressed in liver, has been involved in regulation of triglyceride metabolism, plasma lipid levels, serum adipokine levels and cardiovascular traits. A single-nucleotide polymorphism rs662799 ( − 1131A > G), 2 Kb upstream in the promoter region of this gene, causes decrease in the concentration of the product coded by this gene; hence, it may be responsible for impairments in normal function of the gene, ultimately leading to disease condition. Keeping in view the importance of APOA5 gene, the aim of the present study was to examine the association of genetic variant rs662799 of APOA5 gene with two quantitative traits simultaneously, viz. body mass index and blood pressure.ResultsThe study involved a population of 246 subjects from North Indian region. Measurements of morphometric and physio-metric parameters were recorded using standard measures. Genotyping of APOA5 gene polymorphism (rs662799) using Tetra-primer amplification refractory mutation system PCR was performed. Statistical analyses were carried out using MS-Excel and SigmaPlot, and significance level was setup as p < 0.05. The allelic distribution of rs662799 polymorphism in this population was 77% for major allele (A) and 23% for minor allele (G). Significant association of rs662799 with increased body mass index and blood pressure was observed, with the presence of allele G. Under recessive genetic model, rs662799 polymorphism conferred a 17.71-fold risk of elevated body mass index (OR = 17.71, p < 0.001, CI (95%) = 4.05–77.46), and for increase in blood pressure, 3.79- and 3.83-fold risk of systolic blood pressure and diastolic blood pressure (OR = 3.792, p = 0.023, CI (95%) = 1.25–11.509 and OR = 3.83, p = 0.012, CI (95%) = 1.375–10.68, respectively) was observed. Under dominant genetic model, it showed a 3.060-fold risk of increase in body mass index (OR = 3.060, p < 0.001, CI (95%) = 1.78–5.25).ConclusionsG allele of rs662799 of APOA5 gene showed significant susceptible association with BMI and BP. This study may be helpful for clinicians and researchers to investigate the diagnostic and prognostic value of the gene in question.