TT Genotype Research Articles

Genetic variations in Interferon-Induced with Helicase C Domain 1: Impact on COVID-19 risk and severity in the Moroccan population

BackgroundThe clinical spectrum of COVID-19 varies considerably, ranging from asymptomatic cases to severe disease and even death. This variability can partly be attributed to genetic differences in genes associated with inflammation and immune responses. Among these genes, Interferon Induced with Helicase C Domain 1 (IFIH1), which codes for a cytoplasmic sensor, plays a crucial role in detecting SARS-CoV-2 viral RNA and initiating the antiviral interferon (IFN) response, thereby constituting a key element of innate immune defense. AimThis study aims to examine the association between genetic variants in the IFIH1 gene and susceptibility to, as well as the severity of, COVID-19 in the Moroccan population. Materials and MethodsWe conducted a case-control study involving 299 COVID-19 positive patients (149 severe, 150 benign) and 145 uninfected-SARS-CoV-2 controls. We determined the genotypes of two functional variants, rs1990760 (Ala946Thr) and rs3747517 (His843Arg), in the IFIH1 gene using predesigned TaqMan real-time allelic discrimination assay. ResultsOur results indicated that the TT genotype of rs1990760 was associated with increased susceptibility to SARS-CoV-2 under a recessive model (odds ratio [OR] = 2.22, 95 % confidence interval [CI] 1.28–3.84, P=0.003). Conversely, the CT genotype appeared to confer protection against SARS-CoV-2 infection (OR=0.58, 95 % CI 0.38–0.91, P=0.016) and COVID-19 severity (OR=0.56, 95 % CI 0.34–0.91, P=0.019). No significant association was found between rs3747517 and the risk of hospitalization or infection susceptibility. ConclusionThese findings underscore the significance of genetic variability in the IFIH1 gene in shaping individual responses to SARS-CoV-2 in the Moroccan population.

Genetic association of the kynurenine pathway to suicidal behavior

Suicidal behavior has been associated with dysfunctions in the kynurenine pathway, including alterations in the levels of neuroprotective and neurotoxic metabolites. Changes in the catalytic activity of enzymes within the pathway may contribute significantly. Variations in the genes encoding enzymes within the pathway can significantly affect their catalytic activity, playing a crucial role in the process. To explore this possibility, we hypothesized that these genetic variations would occur more frequently in patients with a history of suicidal behavior compared to non-suicidal individuals. Thus, we investigated the relationship between a history of suicide attempts and five single nucleotide polymorphisms (SNPs) within genes involved in the kynurenine pathway: IDO1 (rs7820268), IDO2 (rs10109853), KMO (rs1053230), KAT1 (rs10988134), and ACSMD (rs2121337). Our sample comprised 849 subjects: 325 individuals who had attempted suicide in their lifetime (SAs), 99 individuals with a history of major depression disorder but no previous suicide attempts (non-SAs), and 425 non-psychiatric controls (CTRL). We performed SNP association analyses using codominant, dominant, and recessive models. Adjustment for sex and multiple comparisons was applied. After adjustment, the analysis revealed that SAs showed a significantly higher frequency of T alleles and TT genotypes of the rs1053230 SNP compared to CTRL across nearly all models. Furthermore, in the recessive model, non-SAs displayed a higher prevalence of the TT genotype of the rs10109853 SNP compared to CTRL.The rs1053230 and rs10109853 SNPs could play a role in the previously observed metabolic dysregulation among SAs and non-SAs, respectively. To validate our findings, it is crucial to conduct functional analyses to investigate the impact of rs10109853 and rs1053230 SNPs on the expression and/or catalytic activity of the corresponding enzymes.

Association Between IFN-λ4 rs12979860 And rs11322783 Polymorphisms with Spontaneous Clearance In Chronic Hepatitis B

Many studies have been published on the association between IFN-λ3 and IFN-λ4 polymorphisms and treatment related or spontaneous clearance of chronic hepatitis C. To date there is little known about the impact of IFN-λ4 polymorphisms on the natural history of chronic hepatitis B(CHB). This study aimed to investigate the role of IFN-λ4 polymorphisms on the course of CHB and to influence the presence of spontaneous clearance (SC) in CHB patients. One hundred and twenty-two patients who had CHB, and 81 subjects who had spontaneous resolution of HBV were analyzed regarding IFN-λ4 rs12979860 and rs11322783 single‑nucleotide polymorphisms. We couldn’t found any significant difference between CHB groups and SC groups in terms of IFN-λ4 rs12979860 polymorphisms and, the CC, C/T and TT genotypes represented 49%, 45% and 5% of CHB patients and, %46, 43% and 11% of SC group respectively (p=0.65). On the other hand, in IFN-λ4 rs11322783 polymorphisms analysis, recessive G/G allele was more common in SC group compared to CHB group (5% vs 16%, p=0.04; OR: 3,55). Moreover, non-G/G genotypes had significantly higher in CHB patients compared to SC group (95% vs 84%, p=0.013; OR:3.55). Our results suggest that IFN-λ4 rs11322783 polymorphism may be a predictor of spontaneous clearance in HBV infected patients. The role of IFN-λ4 polymorphisms needs to be investigated in the natural history of HBV.

TM6SF2-rs58542926 genotype has opposing effects on incidence of hepatic and cardiac events in a community cohort: TM6SF2 effects on liver and cardiac outcomes.

TM6SF2-rs58542926-T is associated with increased cirrhosis and modestly decreased coronary artery disease prevalence. However, relative effects of TM6SF2 genotype on major adverse cardiovascular events (MACE) vs. liver-related events (LRE) is not known. We utilized the UK Biobank, a prospective cohort with genetic and inpatient diagnosis data. The primary predictor was TM6SF2-rs58542926 genotype and the primary outcomes were MACE and LRE. Effects were reported as subhazard ratios (sHR) and 10-year cumulative incidence by Fine-Gray competing risk analyses. >430,000 individuals met inclusion criteria. TM6SF2-rs58542926-TT genotype (vs. CC) was associated with higher incidence of LRE (adjusted sHR 3.16, 95% confidence interval [CI] 1.86-5.37) and lower incidence of MACE (adjusted sHR for TT vs. CC genotype 0.76, 95% CI 0.63-0.91 ). In individuals with Fibrosis-4 (FIB4) <1.3, 1.3-2.67, and >2.67, 10-year LRE incidence in TM6SF2-rs58542926-TT vs. CC individuals was 0.08% vs. 0.06% (p>0.05), 0.81% vs. 0.20% (p<0.0001), and 10.5% vs. 3.4% (p=0.00094), respectively. The corresponding values for MACE were 3.8% vs. 5.1% (p=0.032), 6.4% vs. 8.2% (p=0.040), and 17.1% vs. 12.4% (p>0.05). The absolute decrease in MACE with rs58542926-TT (vs. CC) genotype exceeded the absolute increase in LRE in all groups but FIB4>2.67. Associations of TM6SF2 genotype with LRE/MACE were significant in men but not women. TM6SF2-rs58542926-T allele was also associated with increased hepatic steatosis and corrected T1 time by magnetic resonance imaging, with greater effect sizes in men than women. TM6SF2 genotype has opposite effects on LRE vs. MACE incidence, and absolute effects on MACE were greater except in those with highest FIB4 scores. Effects were strongest in men. These findings clarify implications of TM6SF2 genotype based on personalized clinical risk.

Polymorphism rs564398 of the ANRIL Gene as a Coronary-Artery-Disease-Associated SNP in Diabetic Patients of the Kazakh Population.

A cardiovascular complication of type 2 diabetes mellitus like coronary artery disease is influenced by a complex interplay between environmental, phenotypic, and genetic factors. The genetic mechanisms in the development of this pathology are not established. This study aims to evaluate the association of polymorphisms rs1011970, rs62560775, and rs564398 from the 9p21.3 locus with coronary artery disease in diabetic patients of the Kazakh population. A total of 343 people participated in the case-control study: the control group consisted of 109 people with type 2 diabetes and coronary artery disease, while the control group included 234 people. Genotyping was performed using real-time PCR. Statistical analysis was carried out using Chi-square methods and calculating odds ratios (OR) with 95% confidence intervals (CI). According to the results, only the rs564398 polymorphism of the ANRIL gene was associated with coronary artery disease (p = 0.04). The CC genotype increased the risk of developing coronary artery disease by more than 1.5 times (1.62 (1.02-2.56)), whereas the TT genotype reduced the risk of coronary artery disease (0.39 (0.17-0.91)). The remaining polymorphisms, rs1011970 and rs62560775, were not associated with coronary artery disease. Thus, this research further elicits the association of the ANRIL gene with cardiometabolic disease.

Study on the relationship between KCNQ1 gene-environment interaction and abnormal glucose metabolism in the elderly in a county of Hechi City, Guangxi.

This study aimed to understand the potassium voltage-gated channel KQT-like subfamily, member 1 gene polymorphism in a rural elderly population in a county in Guangxi and to explore the possible relationship between its gene polymorphism and blood sugar. The 6 SNP loci of blood DNA samples from 4355 individuals were typed using the imLDRTM Multiple SNP Typing Kit from Shanghai Tianhao Biotechnology Co. The data combining epidemiological information (baseline questionnaire and physical examination results) and genotyping results were statistically analyzed using GMDR0.9 software and SPSS22.0 software. A total of 4355 elderly people aged 60 years and above were surveyed in this survey, and the total abnormal rate of glucose metabolism was 16·11 % (699/4355). Among them, male:female ratio was 1:1·48; the age group of 60-69 years old accounted for the highest proportion, with 2337 people, accounting for 53·66 % (2337/4355). The results of multivariate analysis showed that usually not doing farm work (OR 1·26; 95 % CI 1·06, 1·50), TAG ≥ 1·70 mmol/l (OR 1·19; 95 % CI 1·11, 1·27), hyperuricaemia (OR 1·034; 95 % CI 1·01, 1·66) and BMI ≥ 24 kg/m2 (OR 1·06; 95 % CI 1·03, 1·09) may be risk factors for abnormal glucose metabolism. Among all participants, rs151290 locus AA genotype, A allele carriers (AA+AC) were 0.70 times more likely (0.54 to 0.91) and 0.82 times more likely (0.70 to 0.97) to develop abnormal glucose metabolism than CC genotype carriers, respectively. Carriers of the T allele at the rs2237892 locus (CT+TT) were 0.85 times more likely to have abnormal glucose metabolism than carriers of the CC genotype (0.72 to 0.99); rs2237897 locus CT gene. The possibility of abnormal glucose metabolism in the carriers of CC genotype, TT genotype and T allele (CT + TT) is 0·79 times (0·67-0·94), 0·74 times (0·55-0·99) and 0·78 times (0·66, 0·92). The results of multifactor dimensionality reduction showed that the optimal interaction model was a three-factor model consisting of farm work, TAG and rs2237897. The best model dendrogram found that the interaction between TAG and rs2237897 had the strongest effect on fasting blood glucose in the elderly in rural areas, and they were mutually antagonistic. Environment-gene interaction is an important factor affecting abnormal glucose metabolism in the elderly of a county in Hechi City, Guangxi.

Protective role of SIRT1 (rs3758391 T &gt; C) polymorphism against T2DM and its complications: Influence on GPx activity

AbstractBackground and AimsSirtuin‐1 (SIRT1) has antidiabetic effects through the regulation of insulin secretion and modulation of inflammation. The SIRT1 rs3758391 gene polymorphism affects the level of SIRT1. The current study aimed to investigate the possible influence of SIRT1 gene variants in relation to oxidative stress parameters on the susceptibility to type 2 diabetes mellitus (T2DM) and its microvascular complications.MethodsIn this case‐control study 398 individuals including 300 patients with T2DM (100 T2DM without complication, 100 diabetic neuropathy patients and 100 patients with diabetic retinopathy) and 98 healthy subjects were studied for SIRT1 rs3758391 T &gt; C variants. Also, the glutathione peroxidase (GPx) activity and the levels of glutathione (GSH), malondialdehyde (MDA), total antioxidant capacity (TAC), and total oxidative status (TOS) were determined by colorimetric methods. SIRT1 genotypes were detected using the polymerase chain reaction‐restriction fragment length polymorphism method.ResultsThe C allele of SIRT1 reduced the risk of T2DM, diabetic neuropathy and diabetic retinopathy. Significantly lower levels of GSH, GPx, and TAC were found in diabetic patients compared to control group. However, the level of MDA was significantly higher in patients compared to healthy individuals. Considering all individuals, the GPx activity increased in the presence of the SIRT1 CC, and TC genotypes compared to the TT genotype. Among all studied individuals the activity of GPx was significantly higher in normal body mass index (BMI) subjects than overweight, and obese individuals. However, among overweight and obese diabetic, diabetic retinopathy and diabetic neuropathy patients the mean level of TOS was significantly higher compared to patients with normal BMI.ConclusionsOur findings suggest a protective role for SIRT1 C allele against T2DM and diabetic neuropathy and diabetic retinopathy. We found in the presence of this allele the GPx activity increased. Also, we detected an enhanced oxidative stress level among overweight and obese patients with diabetes and its complications that could be involved in the pathogenesis of the disease.

Does the LPA genotype have a role in coronary artery disease risk beyond Lp(a) values?

Abstract Introduction High lipoprotein(a) [Lp(a)] concentrations are one of the most important genetically determined risk factors for coronary artery disease (CAD). Many functional single nucleotide polymorphisms (SNPs) of the LPA gene have pronounced effects on Lp(a) concentrations. Studies show that rs3798220 polymorphism is strongly associated with Lp(a) concentration and also with risk of CAD. Goal: To evaluate if LPA rs3798220 T&amp;gt;C is associated with CAD beyond its effect on Lp(a) levels. Methods We performed a case-control study with 3,157 individuals (1,721 CAD patents and 1,436 controls). The LPA rs3798220 T&amp;gt;C was genotyped with the TaqMan PCR assay (Applied Biosystems 7300 Real-Time). This variant has a minor allele frequency (MAF) &amp;lt;2%; hence, the risk homozygous CC is a rare genotype, and we used the heterozygous CT in our analysis. Laboratory analysis was performed, and Lp(a) biochemical levels were measured in the cases and controls. Chi-squared tests were used to determine differences by genotype in CAD association (in cases and controls). We also reported a multivariate logistic regression to test if this LPA variant is still independently associated with CAD after adjustment to Lp(a) levels and traditional risk factors for CAD. Results Wild-type genotype TT was increased in the group without CAD, whereas the genotype TC was higher in patients with CAD (p&amp;lt;0.0001). After multivariate logistic regression, adjusted for traditional risk factors, the TC genotype remained in the equation as an independent risk factor for CAD (OR=2.36; 95%CI: 1.54–3.61; p&amp;lt;0.0001). When the multivariate regression analysis is adjusted for traditional risk factors plus Lp(a) levels, the TC genotype remains in the equation as independently associated with CAD despite being substantially attenuated (OR=1.67; 95%CI: 1.07–2.60; p=0.025). Conclusion LPA rs3798220 T&amp;gt;C may be an independent risk factor for CAD beyond the effect of rising Lp(a) levels. Perhaps testing for the genetic determinants of Lp(a) relative to direct measurement of Lp(a) level could provide additional prognostic utility.

Influence of recipient KRAS gene rs712 polymorphisms on the overall survival rate of hepatocellular carcinoma after hepatic transplantation

Hepatocellular carcinoma (HCC) recurrence appears commonly after liver transplantation (LT), and it severely affected the long-term survival of patients. Previous studies have proved that Rap1A is involved in hepatocarcinogenesis and metastasis, and demonstrated the significant association between KRAS rs712 polymorphism and HCC. However, the relationship between KRAS rs712 polymorphism and HCC recurrence after LT remained unclear. A total of 93 HCC patients who underwent LT from March 2008 to Dec 2015 was analyzed. The genotypes of both donors and recipients had been confirmed as KRAS rs712. The independent risk factors that associated with HCC recurrence were investigated with univariate and multivariate logistic regression analysis. The recurrence-free (RFS) and overall survival (OS) were calculated with Cox regression analysis. The KRAS rs712 genotype frequencies were determined using the Χ2 test and the minor allele frequencies (MAFs) of KRAS rs712 genotypes were calculated by Hardy–Weinberg equilibrium. We found that the recipient KRAS rs712 polymorphism was significantly associated with HCC recurrence after LT. Moreover, the Milan criteria, microvascular invasion and recipient KRAS rs712 genotype were proved to be independent risk factors for HCC recurrence after LT. Patients with donor TG/TT genotypes had a significantly higher RFS and OS than TT genotype. The TNM stage, microvascular invasion, Milan criteria, treatment and recipient KRAS rs712 genotype were independent factors for the RFS of LT patients. Recipient KRAS rs712 polymorphism is associated with HCC recurrence after liver transplantation and plays as a promising bio-predictor of overall survival rate of HCC risks after hepatic transplantation.

Association of the GRIK4 rs1954787 polymorphism with clinical response in antidepressant-treated depressed patients: results from a prospective cohort and meta-analysis.

Major Depressive Disorder (MDD) is the leading cause of disability worldwide. Genetic factors influence the effect of its main treatment option, antidepressant drugs (ATD). The GRIK4 rs1954787(T>C) genetic polymorphism was associated with response following 1-3 months of ATD treatment in some studies, but not others. We aimed to analyze its association with clinical outcomes in a cohort of 6-month ATD-treated patients and meta-analysis. Clinical data were obtained at baseline and after 1 (M1), 3 (M3), and 6 (M6) months of ATD treatment in 390 patients of the METADAP cohort. Mixed-effects models were used to assess the association of the GRIK4 rs1954787 polymorphism with the Hamilton Depression Rating Scale (HDRS) score and response and remission rates across time. Meta-analyses of ATD treatment response were performed with previously meta-analyzed data and METADAP. Compared to C allele carriers at M3 (n = 200), TT homozygotes at M3 (n = 66) had higher HDRS scores (coef = 3.37, 95% CI [1.30-5.54], Padj = 0.0046) and lower remission rates (OR = 0.36, 95% CI [0.16-0.76], Padj = 0.029). At M6, greater differences between TT homozygotes (n = 53) and C allele carriers (n = 152) were observed for HDRS scores (coef = 4.68, 95% CI [2.17-7.18], Padj = 0.00091) and remission rates (OR = 0.26, 95% CI [0.12-0.54], Padj = 0.0016). Meta-analyses of response were significant when comparing C vs T alleles (OR = 1.31, 95% CI [1.06-1.62], P = 0.014) and CC vs TT genotypes (OR = 1.63, 95% CI [1.10-2.38], P = 0.019). Altogether, our results support an association of the GRIK4 rs1954787(T>C) polymorphism with clinical improvement following ATD treatment. This association should be further assessed in other longitudinal studies. Its position within the glutamatergic system may help in understanding the mechanism of ATD action.

Gene polymorphisms of miR-323b and miR-1343 that regulate kininogen L are associated with schizophrenia susceptibility: A preliminary population‑based study.

miR-SNP is a type of functional single nucleotide polymorphism (SNP) that affects the regulatory functions of miRNA genes, miRNA binding sites, or components of miRNA biogenesis. This study aimed to explore the relationship between miRNA gene polymorphisms that regulate the kininogen L protein and schizophrenia (SCZ). Bioinformatics methods predicted miRNA gene polymorphism sites regulating the kininogen L protein. The polymorphisms of rs56103835, rs6513496, rs651349, and rs2986407 were detected using imLDR multiple SNP typing technologies in 513 SCZ patients and 509 controls. The association of miR-SNP variations with SCZ susceptibility and symptoms was evaluated using SNPstat to determine the optimal inheritance model. Generalized multifactor dimensionality reduction (GMDR) analysis and logistic regression were used to calculate miR-SNP interactions. The association between hsa-miR-323b-rs56103835 and SCZ was statistically significant under the dominant model. The result of gene-gene interaction showed that the three-factor model (rs56103835 / rs2986407 / rs2155248) was the best, but it could not be considered significantly related to SCZ. Additionally, SCZ patients with the CC or CT genotype on rs2986407 were more likely to experience auditory hallucinations than those with the TT genotype. Our data revealed that the mutation of hsa-miR-323b-rs56103835 from C to T was associated with susceptibility to SCZ. The mutation of hsa-miR-1343-rs2986407 from T to C increases the risk of auditory hallucinations in SCZ patients.

Milk traits characterization and association studies with DGAT1 polymorphisms in Bagnolese sheep.

The Bagnolese sheep is an authochtonous dual-purpose breed (milk and meat) reared in the Campania region, whose milk is used to produce Pecorino Bagnolese cheese. Genetic information on this sheep is extremely limited, especially regarding genes affecting productions. The aim of this study was to investigate milk production traits in Bagnolese sheep and the variability of diacylglycerol acyltransferase 1 (DGAT1) gene and its effects on milk production. Milk quantity was recorded during the morning milking, while Kjeldahl and Gerber methods were used to assess protein and fat percentage (w/v) of collected milk samples. Two PCR-RFLP protocols using BamHI and MspI endonucleases for genotyping of g.5553C>T and g.8539C>T at DGAT1 locus, respectively, were set up. Bagnolese sheep milk shows high fat and protein concentrations. Genotyping revealed a high frequency of the g.5553C and g.8539C alleles (0.56 and 0.95, respectively). The association study between the SNP g.5553C>T and milk traits showed that animals with the CT genotype had a higher percentage of fat produced per milking than those with the CC and TT genotypes (p<0.01). Similar results were found for protein yield percentage, with CT individuals being more productive than CC individuals (p<0.01). Bagnolese sheep milk parameters found are associated with high yields in the resulting dairy products. CT genotype at the SNP g.5553 of DGAT1 has shown a positive association with fat and protein milk yield percentage suggesting it could be considered a marker to improve productions of this breed. Finally, the new genotyping techniques used for this study enable a cheap and reliable characterization of two DGAT1 SNPs in sheep.

VDR gene polymorphisms rs731236 and rsS2228570 affect vitamin D levels in people of the Kaliningrad region

Vitamin D is an essential micronutrient that is involved in numerous biological processes. It not only keeps bones healthy, but also has a protective effect on the cardiovascular system, the pancreas and fatty tissue. Around 50% of the world’s population suffers from vitamin D deficiency or insufficiency. The prevalence of these diseases is significantly higher in obese people, regardless of age and place of residence. The presence of polymorphisms in the VDR gene (vitamin D receptor) can explain individual differences in the concentration of vitamin D 25(OH) in blood serum. Of particular interest are the effects of the polymorphisms rs731236 and rs2228570 on vitamin levels. Thus, the VDR polymorphism rs731236 is a synonymous substitution, whereas the polymorphism rs2228570 is a non-synonymous substitution. The article investigated the polymorphisms of the VDR gene rs2228570 (T/C), rs731236 (T/C) and determined their association with blood vitamin D levels in people from the Kaliningrad region with different body mass index (BMI). The material for the study was venous blood taken in the morning on an empty stomach from 232 people (mean age 50±13.5 years, 103 men and 129 women). The vitamin D content in the blood was determined by ELISA and the polymorphisms of the VDR gene were analyzed by PCR. In individuals with a BMI 30 kg/m2, changes in the lipid profile and liver function tests were recorded. The vitamin D level did not depend on the BMI of the study participants. Significant changes in blood vitamin D levels were found depending on the distribution of the VDR genotype. Vitamin D levels were higher in individuals with the CC genotype than in the TT and CT genotypes of the rs2228570 polymorphism and did not depend on BMI. In contrast, the presence of the rs731236 polymorphism in the VDR gene is associated with BMI. In obesity, vitamin D levels are therefore only reduced in people with the TT genotype of the rs731236 polymorphism, but not in people with the CC and TC genotype.

Cognitive Impairments Related to COMT and Neuregulin 1 Phenotypes as Transdiagnostic Markers in Schizophrenia Spectrum Patients.

Background: Research on the interaction between antipsychotic treatment and cognitive dysfunction in schizophrenia spectrum disorders (SSDs) is extensive, yet the role of genetic polymorphisms in catechol-O-methyltransferase (COMT) and neuregulin 1 (NRG1) remains underexplored. Methods: This study evaluates the impact of COMT (rs4680) and NRG1 (rs3924999 and rs35753505) polymorphisms on cognitive functions in SSD patients. A cross-sectional study was conducted with fifty-four patients, assessed using the Positive and Negative Syndrome Scale (PANSS) and the CNS Vital Signs battery. Results: Significant cognitive function differences were observed across SSD diagnostic categories (p < 0.001). The NRG1 rs35753505 TT genotype was significantly associated with better verbal memory performance compared to the CC genotype (p = 0.03), while no significant differences were observed for other genotypes. The NRG1 rs3924999 AA genotype showed superior reasoning performance compared to AG and GG genotypes (p = 0.01), with AG and GG associated with lower scores (p = 0.01 and p = 0.02, respectively). Additionally, the COMT Val158Met genotype significantly influenced processing speed, with patients at the first episode of psychosis showing higher scores than chronic patients (p = 0.01). Conclusions: These findings suggest that NRG1 and COMT polymorphisms may influence cognitive domains in schizophrenia spectrum disorders, potentially informing personalized treatment and cognitive rehabilitation strategies.

RNA-seq and whole-genome re-sequencing reveal Micropterus salmoides growth-linked gene and selection signatures under carbohydrate-rich diet and varying temperature

This study was performed on Micropterus salmoides to determine growth-linked gene and single nucleotide polymorphism (SNP) markers under carbohydrate diet and varying temperature through RNA-seq and whole-genome re-sequencing. The results showed that growth-related genes were primarily enriched in the fat digestion and absorption signaling pathway, playing a role in lipid transport and metabolism. Fatty acid binding protein 6, bile salt-activated lipase-like, lysophosphatidylcholine acyltransferase 2, phospholipase A2, minor isoenzyme-like, and phospholipase A2, group IB (pancreas) were identified as the crucial genes. The differentially expressed genes between high and low temperatures were enriched in the pentose phosphate pathway, with carbohydrate transport and metabolism were most affected by temperature. Major facilitator superfamily domain containing 10, phosphogluconate dehydrogenase, fructose-1,6-bisphosphatase 1a, and spinster homolog 3 transcript variant X1(spns3) were the shared genes affected by temperature. From all the common genes, 10 growth-associated SNP markers were identified. The TT genotype at rs7781 was associated with lower body weight, while AA genotype at rs31434173 and CC genotype at rs31435313 showed positive correlation with body weight. Analogously, the GG genotype at rs31436887 and AA genotype at rs31438769 also found to characterize better growth performance. At low temperature, individuals with the AA genotype at rs11506587 and rs31435313 exhibited the slowest growth. For the genotypes labeled with rs11510589, the GG individual grew faster than the AA individual, whereas the opposite phenomenon occurred in these genotypes when labeled with rs11511314. The genotypes at rs32970704 and rs32967921 showed no growth correlation. The AA genotype at rs31435313 in spns3 had the slowest growth under a carbohydrate-rich diet regardless of the temperature. Our study presents candidate genes and SNP markers associated with growth influenced by carbohydrate and temperature, providing basis for the development of M. salmoides strain that better accepts carbohydrate diets at varying temperature.

Association between methylenetetrahydrofolate reductase C677T polymorphisms and male oligozoospermia, asthenozoospermia or oligoasthenozoospermia: a case–control study

Mutation of methylenetetrahydrofolate reductase (MTHFR) C677T leads to the decrease of folate utilization and the impairment of spermatogenesis. This study attempts to investigate the association between MTHFR C677T polymorphisms and nonobstructive oligozoospermia, asthenozoospermia or oligoasthenozoospermia in the Chinese population. The study cohort comprised 189 patients diagnosed with oligozoospermia, asthenozoospermia or oligoasthenozoospermia, and 626 controls based on clinical examinations. The MTHFR c.677 genotype of all subjects was determined by fluorescence staining in situ hybridization and the significance of different genotype frequencies was further analyzed by Chi-square test. The results showed that the frequency of MTHFR 677 CT genotype in the oligozoospermia, asthenozoospermia and oligoasthenozoospermia group was 33.3%, 38.3% and 44.0% respectively, whereas it was 47.3% in the control group. The P value of Chi-square test was 0.070, 0.103 and 0.654, respectively. The frequency of MTHFR 677 TT genotype in the oligozoospermia, asthenozoospermia and oligoasthenozoospermia group was 31.1%, 11.7% and 18.0% respectively, while that in the control group was 19.5%. The P value of Chi-square test was 0.061, 0.070 and 0.066, respectively. Collectively, there is a weak association between MTHFR C677T polymorphisms and oligozoospermia, asthenozoospermia or oligoasthenozoospermia within the current Chinese population cohort.

EDNRA affects susceptibility to large artery atherosclerosis stroke through potential inflammatory pathway

This study aimed to explore the potential association between Endothelin type A receptor (EDNRA) genetic polymorphisms and susceptibility to large artery atherosclerotic stroke (LAA), as well as the involvement of inflammation mechanisms. We recruited Han Chinese patients with LAA and age- and sex-matched controls. The distribution of alleles and genotypes for 16 single nucleotide polymorphisms (SNPs) in EDNRA was analyzed using dominant, recessive, and co-dominant genetic models between cases and controls. We quantified the mRNA and protein levels of EDNRA and NLRP3 genes, and concentrations of inflammatory factors (TNFα, IL-1β, IL-6, IL-8, IL-10, IL-18, and CCL18) in peripheral blood samples randomly selected from cases and controls. We also investigated the relationship between these SNPs, gene expression patterns and inflammatory factor levels. A total of 428 LAA cases and 434 controls were enrolled in this study. The results showed that rs5343 TT genotype of EDNRA was significantly associated with an increased risk of LAA (OR = 3.243, 95%CI = 1.608–6.542, P = 0.001). It also demonstrated a significant upregulation level of NLRP3 as well as higher concentrations of IL-10, IL-18, and CCL-18 in cases compared to controls. Besides, we discovered that the EDNRA polymorphisms were linked to NLRP3, IL-6, IL-10, and IL-18 levels in cases. There existed a positive correlation between EDNRA transcription levels and both NLRP3 transcript levels (r = 0.437, p < 0.001) and IL-18 concentrations (r = 0.212, p < 0.001). EDNRA is linked to susceptibility of LAA. This association may be attributed to the NLRP3-mediated inflammatory pathway.

Association between rs8192678 C/T polymorphism of the PPARGC1A gene and metabolically associated fatty liver disease in obese children living in the Moscow region

Over the past 30 years, the incidence of childhood obesity has quadrupled, leading to a rise in metabolically associated fatty liver disease (MAFLD), which has multifactorial genesis. Numerous studies highlight a significant genetic contribution to the development and severity of MAFLD. Purpose of the study. Тo determine the distribution of alleles and genotypes of the rs8192678 C/T polymorphism of the PPARGC1A gene and its relationship with the development of MAFLD in obese children living in the Moscow region. Materials and methods. The study included 87 children with exogenous constitutional obesity. The children were divided into two groups: group I - obesity without MAFLD (n = 43), group II - obesity with MAFLD (n = 44). The association of genotypes with the risk of developing MAFLD was studied in various genetic models. Results. 43 (49.4%) children had genotypes containing the T allele: 4 (4.6%) - homozygous TT genotype, 39 (44.8%) - heterozygous CT genotype. The CC genotype was detected in 44 (50.6%) children. The frequency of allele C was 73%. Carriers of the T allele have almost twice the risk of developing MAFLD than сarriers of the C allele (OR = 2.08 (95% CI: 1.05-4.24), p = 0.041). Conclusion. Тhe rs8192678 polymorphism increases the risk of developing MAFLD already in childhood, and with the homozygous TT genotype, this risk more than doubles. Studying the genetic contribution to the development of MAFLD enables a comprehensive approach to assessing individual risks of each patient.

MiR-559 rs58450758 polymorphism is associated with colorectal cancer risk and prognosis in Chinese Han population.

Aim: This research examined the correlation between miR-559 rs58450758 and the clinical pathological characteristics and prognosis of CRC.Materials & methods: RT-qPCR was utilized to assess the miR-559 expression levels. Chi-square test was used to investigate the relationship between miR-559 and clinical features. The association between rs58450758 different genotypes and CRC risk, as well as clinical pathological parameters, was explored, utilizing logistic regression analysis and chi-square tests. The Cox regression model and Kaplan-Meier analysis evaluated overall survival in individuals with CRC.Results: The miR-559 was down-regulated in CRC patients' serum. The expressions of miR-559 were significantly associated with tumor size, differentiation, TNM stage and lymph node metastasis. The rs58450758 TT genotype and T allele carriers were more prevalent among CRC patients. The rs58450758 polymorphism was notably linked to tumor size, differentiation, TNM stage and lymph node metastasis in CRC patients. Furthermore, CC genotype carriers exhibited a longer survival period than CT/TT genotypes within the CRC population.Conclusion: The miR-559 rs58450758 polymorphism exhibits promise as a potential biomarker for prognosticating the outcomes of CRC.

Interleukin-1 Beta rs16944 and rs1143634 and Interleukin-6 Receptor rs12083537 Single Nucleotide Polymorphisms as Potential Predictors of COVID-19 Severity.

Host genetic variation has been recognized as a key predictor of diverse clinical sequelae among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients. Insights into the link between the Interleukin-6 receptor (IL-6R) and Interleukin-1 beta (IL-1β) genetic variation and severe coronavirus disease 2019 (COVID-19) are crucial for developing new predictors and therapeutic targets. We aimed to investigate the association of IL-6R rs12083537, IL-1β rs16944, and IL-1β rs1143634 SNPs with the severity of COVID-19. Our study was conducted on 300 COVID-19-negative individuals (control group) and 299 COVID-19-positive cases, classified into mild, moderate, and severe subgroups. Analyses of IL-1β (rs16944, rs1143634) and IL-6R (rs12083537) SNPs' genotypes were performed using qPCR genotyping assays. The IL-1β (rs16944) CC genotype and IL-6R (rs12083537) GG genotype were substantially related to COVID-19 severity, which was also associated with comorbidities and some laboratory parameters (p < 0.001). The IL-1β (rs1143634) TT genotype was found to be protective. Likewise, the IL-1β (rs16944) CC genotype was associated with increased mortality. IL-1β rs16944 and IL-6R rs12083537 SNPs are promising potential predictors of SARS-CoV-2 disease severity. Meanwhile, the rs1143634 SNP T allele was protective against severity and mortality risk.