Assessing the association of rs7574865 STAT4 gene variant and type 1 diabetes mellitus among Egyptian patients.
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ABSTRACT: Background
Variants in the signal transducer and activator of transcription 4 (STAT4) gene have an important role in the incident of multiple autoimmune diseases including type 1 diabetes mellitus (T1D). It is a genetically related auto-immune disorder that resulted from T cell-mediated destruction of pancreatic cells that are in control for the production of insulin in the blood. The current study aimed to clarify the role of STAT4 (rs7574865) variant allelic and genotypic variations in the susceptibility to type 1 diabetes among Egyptians by using the real-time PCR.Results
A total of 100 patients and 100 controls were genotyped for rs7574865, and the biochemical and anthropometric parameters were measured to show that type 1 diabetic patients had significantly higher levels of HbA1c and triglycerides compared to non-diabetic individuals (P < 0.05). And genetically, the T allele and GT genotype have a significant correlation with diabetes type 1.Conclusion
It was confirmed by this study that the rs7574865 T allele and GT genotype have a significant correlation with diabetes type 1 incidence among Egyptian patients.
SUBMITTER: Abdelmajed SS
PROVIDER: S-EPMC8333174 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Age-related macular degeneration (AMD) is a progressive degenerative disease that affects the central part of the retina: the macula. AMD is the most common cause of central vision loss in industrialized countries. Increasing attention is being paid to the study of genetic factors that may influence the manifestation of AMD. STAT4 protein is involved in the pathogenesis of numerous inflammatory processes, so we decided to investigate the association between STAT4 gene polymorphisms (rs10181656, rs7574865, rs7601754, and rs10168266) and age-related macular degeneration.PurposeTo investigate the association between STAT4 (rs10181656, rs7574865, rs7601754, and rs10168266) gene polymorphisms and STAT4 serum levels in patients with age-related macular degeneration.Methods and participantsThe study included 150 individuals with early AMD, 150 individuals with exudative AMD, and 200 healthy subjects. DNA was extracted from peripheral blood leukocytes using the DNA salting-out method, and the genotyping was performed using a real-time polymerase chain reaction (RT-PCR) method. STAT4 serum levels were evaluated using the ELISA method. Statistical analysis was performed using "IBM SPSS "Statistics 29.0" software".ResultsThe study revealed no statistically significant differences in the distribution of genotypes and alleles for the STAT4 polymorphisms (rs10181656, rs7574865, rs7601754, and rs10168266) between patients with AMD and the control group. Similarly, a gender-based analysis did not yield any significant differences in the genotype or allele frequencies. Age group comparisons also showed no statistically significant variations in the presence of these STAT4 polymorphisms between AMD patients and the control group. However, notably, individuals with exudative AMD displayed lower levels of serum STAT4 in comparison to the control group (median (IQR): 0.118 (0.042) vs. 0.262 (0.385), p = 0.005).ConclusionInvestigating STAT4 gene polymorphisms (rs10181656, rs7574865, rs7601754, and rs10168266) did not reveal a significant association with AMD. However, further analysis demonstrated intriguing findings regarding serum STAT4 levels. Exudative AMD patients with at least one G allele of the STAT4 rs10181656 exhibited significantly lower serum STAT4 levels than the control group subjects (p = 0.011). Similarly, those with at least one T allele of STAT4 rs10168266 had lower serum STAT4 levels compared to the control group subjects (p = 0.039). These results suggest a potential link between specific STAT4 genotypes and serum STAT4 levels in exudative AMD patients, shedding light on a novel aspect of the disease.
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Project description:Various loci and genes that confer susceptibility to coronary heart disease (CHD) have been identified in Caucasian populations by genome-wide association studies (GWASs). As type 2 diabetes mellitus (DM) is an important risk factor for CHD, we hypothesized that certain polymorphisms may contribute to the genetic susceptibility to CHD through affecting the susceptibility to type 2 DM. The purpose of the present study was to examine a possible association of type 2 DM in Japanese individuals with 29 polymorphisms identified as susceptibility loci for CHD by meta-analyses of the GWASs. The study subjects comprised of 3,757 individuals (1,444 subjects with type 2 DM and 2,313 controls). The polymorphism genotypes were determined by the multiplex bead-based Luminex assay, which combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. To compensate for multiple comparisons of genotypes, the criterion of a false discovery rate (FDR) ?0.05 was adopted for testing the statistical significance of the association. The comparisons of allele frequencies by the ?2 test revealed that the rs964184 (C?G) of the ZPR1 zinc finger gene (ZPR1) was significantly associated (P=0.0017; FDR=0.050) with type 2 DM. Multivariable logistic regression analysis with adjustment for age, gender and body mass index revealed that rs964184 of ZPR1 was significantly associated (P=0.0012; odds ratio, 1.25; dominant model) with type 2 DM with the minor G allele representing a risk factor for this condition. Fasting plasma glucose levels (P=0.0076) and blood glycosylated hemoglobin contents (P=0.0132) significantly differed among ZPR1 genotypes with the G allele associated with increases in these parameters. ZPR1 may thus be a susceptibility locus for type 2 DM in Japanese individuals.
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Project description:BackgroundEvidence from genetic epidemiology indicates that type 2 diabetes (T2D) has a strong genetic basis. Activated STAT4 has an inflammatory effect, and STAT4 is an important mediator of inflammation in diabetes. Our study aimed to study the association between STAT4 single nucleotide polymorphisms (SNPs) and T2D susceptibility in Chinese Han population.MethodsWe conducted a 'case-control' study among 500 T2D patients and 501 healthy individuals. 5 candidate STAT4 SNPs were successfully genotyped. The association between SNPs and T2D susceptibility under different genetic models was evaluated by logistic regression analysis. 'SNP-SNP' interaction was analyzed and completed by multi-factor dimensionality reduction (MDR). Finally, we evaluated the differences of clinical characteristics under different genotypes by one-factor analysis of variance.ResultsThe overall results showed that STAT4 rs3821236 was associated with increasing T2D risk under allele (OR 1.23, p = 0.020), homozygous (OR 1.51, p = 0.025), dominant (OR 1.36, p = 0.029), and additive models (OR 1.23, p = 0.020). The results of stratified analysis showed that rs3821236, rs11893432, and rs11889341 were risk factors for T2D among participants ≤ 60 years old. Only rs11893432 was associated with increased T2D risk among female participants. There was also a potential association between rs3821236 and T2D with nephropathy risk. STAT4 rs11893432, rs7574865 and rs897200 were significantly associated with lysophosphatidic acid, cystatin C and thyroxine t4, respectively.ConclusionThe genetic polymorphisms of STAT4 is potentially associated with T2D susceptibility of Chinese population. In particular, rs3821236 is significantly associated with T2D risk both in the overall and several subgroup analyses. Our study may provide new ideas for T2D individualized diagnosis/protection.
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Project description:Estrogen might play an important role in type 2 diabetes mellitus pathogenesis. A number of polymorphisms have been reported in the estrogen receptor alpha gene including the XbaI and PvuII restriction enzyme polymorphisms. The aim of this study was to determine if ESRα gene polymorphisms are associated with type 2 diabetes mellitus and correlated with lipid profile. Ninety diabetic Egyptian patients were compared with forty healthy controls. ESRα genotyping of PvuII and XbaI was performed using restriction fragment length polymorphism analysis. Our study showed that there is more significant difference in the frequency of C and G polymorphic allele between patients and control groups in PvuII and XbaI respectively. Also carriers of minor C and G alleles of PvuII and XbaI gene polymorphisms were associated with increased fasting blood glucose and disturbance in lipid profile as there is an increase in total cholesterol, triglycerides and Low density lipoprotein. So findings of present study suggest the possibility that PvuII and XbaI polymorphisms in ERα are related to T2DM and with increased serum lipids among Egyptian population.
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Project description:BackgroundNa+/K+ ATPase enzyme is essential for nerve cell membrane integrity, and reduction in its activity, probably due to ATP1A1 gene polymorphisms, is related to diabetic neuropathy progression. Therefore, the goal of the existent study is to evaluate the Na+/K+ ATPase activity in type 2 diabetes mellitus (T2DM) Egyptian patients with or without neuropathy, search for polymorphism(s) in the highly polymorphic region of ATP1A1 gene, exon 2, and study its (their) associations with T2DM with and without neuropathy.Materials and methodsA total number of 150 individuals were subclassified into healthy controls (n = 30), T2DM without complications (n = 60), and T2DM with neuropathy (n = 60).ResultsThe biochemical results exhibited a significant reduction in fasting C-Peptide and activity of Na+/K+ ATPase in T2DM patients with neuropathy followed by T2DM without complication in comparison with healthy controls. ATP1A1 exon2 was amplified by polymerase chain reaction (PCR) then digested by the PstI restriction enzyme, and the obtained data from restriction fragment length polymorphism-PCR and sequencing revealed the existence of a novel synonymous G94A single nucleotide polymorphism (SNP) at nucleotide 27 in exon 2 of ATP1A1 gene (rs1060366). Diabetic groups had only allele A, while the control group had G allele. Interestingly, individuals carrying AA genotype had a significantly lower Na+/K+ ATPase, C-peptide, and higher glycosylated hemoglobin (HBA1c %) than those having GG genotype, suggesting a possible association for this SNP, and this developed phenomenon of not only T2DM but also diabetic neuropathy.ConclusionThus, allele A of G94A SNP (rs1060366) could be a risk allele for diabetes susceptibility among Egyptian patients.
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Project description:IntroductionType 1 diabetes (T1D) is caused by the autoimmune destruction of pancreatic β cells, resulting from coincident genetic predisposition and some environmental triggers. Signal transducer and activator of transcription 4 (STAT4) gene encodes a transcription factor, which promotes Th1 cell differentiation, interferon γ production, and development of Th17 cells. Polymorphisms of STAT4 are associated with several autoimmune conditions, while studies in T1D provided inconsistent results. This analysis was designed to investigate the association of STAT4 rs7574865 with T1D in Polish children and to assess STAT4 expression in newly diagnosed subjects.Material and methodsRs7574865 was genotyped in 656 T1D children and 782 healthy individuals. STAT4 mRNA expression was analyzed in peripheral blood mononuclear cells (PBMCs) from 29 children with T1D and 27 age-matched controls. β-cell and thyroid-specific serum autoantibodies were assessed with radioimmunoassays.ResultsThe distribution of rs7574865 genotypes and alleles demonstrated significant difference (p = 0.002, p < 0.001, respectively) between patients vs. controls. Carriers of the minor T allele presented earlier T1D onset (p = 0.017). No differences were found in γ-cell autoantibody in genotype-stratified patients (p > 0.050), while anti-thyroid antibodies were more frequent in carriers of the minor allele(p = 0.039 for anti-thyroperoxidase, p = 0.007 for anti-thyroglobulin antibodies, respectively). STAT4 was overexpressed in PBMCs from T1D patients (p = 0.008), especially subjects with two/three circulating β-cell antibodies (p < 0.001).ConclusionsThe study confirms an association of STAT4 rs7574865 with T1D in Polish patients, and provides an evidence for its relationship with an earlier disease onset and concomitant thyroid autoimmunity. STAT4 expression appears elevated in T1D, especially with more severe reaction against β-cell antigens.
| S-EPMC7226553 | biostudies-literature
Project description:Although there are many studies on the relationship between genetic polymorphisms and the incidence of diseases, mechanisms are rarely known. We report the mechanism by which signal transducer and activator of transcription 4 (stat4) rs7574865 promotes the occurrence and progression of hepatocellular carcinoma (HCC). We found that the GG genotype at stat4 rs7574865 was a risk genotype, and STAT4 levels in serum and peritumoral tissue from HCC patients with the GG genotype were significantly higher than those found in TT or TG carriers. Furthermore, HCC patients with the GG genotype or elevated STAT4 levels had poor prognoses. In vitro experiments demonstrated that STAT4 silencing promoted apoptosis and inhibited the invasion and migration of HepG2 and L02 cells. Proteomic analysis of HCC peritumors identified 273 proteins related to STAT4, of which CYP2E1 activity and FGL2 content exhibited the highest positive correlation. The relationship between CYP2E1 and FGL2 was also confirmed in cyp2e1-/- mice and in CYP2E1 inhibitor-treated mice. In conclusion, this study elucidates the mechanism by which the stat4 rs7574865 polymorphism promotes the occurrence and progression of HCC via the Stat4/CYP2E1/FGL2 pathway.
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Project description:ObjectivesConditions of hypoandrogenism in men have been linked to insulin resistance, suggesting that alterations in normal sex steroid physiology could play a role in the pathogenesis of Type 2 diabetes mellitus (T2DM). Sex hormone-binding globulin (SHBG) gene polymorphisms may be the cause of sex steroid alteration. The aim of this work is to study the effect of SHBG gene polymorphisms on the risk of T2DM through its impact on testosterone and oestradiol level in Egyptian men.Subjects and methodsA case control study was performed in the diabetes clinic at Zagazig University Hospital on 185 males with Type 2 diabetes and their matched healthy controls. Two polymorphisms (rs6257 and rs6259) of the gene encoding SHBG were genotyped and serum levels of SHBG, testosterone and oestradiol were measured by enzyme-linked immunosorbent assay (ELISA).ResultsCarriers of rs6257 variant allele (CC or CT) and carriers of rs6259 wild allele (GG) appear to have a high risk of diabetes than carriers of other alleles (OR 2.241, 1.585 and 2.391, respectively). They also showed a significant decrease in plasma level of both SHBG and testosterone and a significant increase in oestradiol blood level compared with carriers of other alleles.ConclusionsSex hormone-binding globulin gene polymorphisms at position rs6257 and rs6259 are associated with higher risk of T2DM in Egyptian men, through lowering circulating levels of SHBG and consequently, lowering testosterone and elevating oestradiol level.
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