Dominant Inheritance Model Research Articles

Дослідження зв'язку фенотипу бронхіальна астма-ожиріння з ER22/23EK і TTH111I поліморфізмами гена глюкокортикоїдного рецептора

(GR) gene with the body mass index (BMI) of patients with bronchial asthma (BA), considering the age of BA onset. Materials and methods. 553 patients with BA and 95 practically healthy persons who previously signed an informed consent to participate in the study were examined. Patients were divided into two clinical groups according to the age of BA onset. Group I included 282 patients with late-onset of asthma (late asthma phenotype), and Group II included 271 patients with early onset (early asthma phenotype). The diagnosis of BA and the severity of the course were established according to the recommendations of GINA-2016 and subsequent versions. Diagnosis of obesity was carried out in accordance with the Order of the Ministry of Health of Ukraine dated August 5, 2009, No. 574, and the European Association for the Study of Obesity (EASO, 2016). The study was approved by the Bioethics Committee of the Medical Institute of Sumy State University. Determination of ER22/23EK (rs 6189/6190) and Tth111I (rs10052957) polymorphisms of the GR gene was performed using the polymerase chain reaction followed by the analysis of restriction fragments. Statistical analysis of the obtained results was carried out using the SPSS-17 program. The results. The analysis of anthropometric parameters showed that among the examined patients with BA, there were 152 (27.5 %) patients with normal body weight (NBW), 206 (37.3 %) were overweight, and 195 (35.2 %) with obesity. Visceral type of obesity was verified among all patients. It was established that among overweight and obese BA patients, there was a higher frequency of GG genotype according to the ER22/23EK polymorphism of the GR gene compared to patients with NBW. Heterozygotes were found 5.6 and 3.5 times more often in patients with normal body weight compared to patients with obesity. Analysis of the ratio of G and A alleles depending on BMI shows a higher frequency of the G allele in obese patients compared to patients with NBW. The distribution of alleles and genotypes according to the Tth111I polymorphism in the examined patients with BA depending on the BMI shows a twice higher frequency of homozygotes for the main C allele in overweight and patients with obesity compared to patients with NBW. Carriers of homozygotes for the minor allele were detected 4.7 times and 2.1 times more often in patients with NBW compared to overweight patients and with obesity. A probable difference in the distribution of alleles and genotypes according to the Tth111I polymorphism of the GR gene was established in patients with early and late BA (p = 0.001). Carriers of homozygotes for the main allele of CC were found more often in patients with early and late BA in the presence of obesity. Conclusions. A higher frequency of the GG genotype according to the ER22/23EK polymorphism of the GR gene and homozygotes according to the main CC allele according to the Tth111I polymorphism of the GR gene in overweight BA patients and with obesity compared to patients with NBW was proven. The protective role of the ER22/23EK polymorphism of the GR gene in relation to the occurrence of obesity in the dominant, superdominant and additive models of inheritance and the Tth111I polymorphism of the GR gene in the superdominant model was established. A higher frequency of carriers of homozygotes for the main C allele in patients with early-onset and late-onset BA in the presence of obesity compared to patients with NBW, a protective role of the Tth111I polymorphism of the GR gene on the risk of developing obesity in patients with late-onset BA in superdominant and recessive models of inheritance was established. Key words: bronchial asthma, obesity, onset, course, ER22/23EK, and Tth111I polymorphisms of the glucocorticoid receptor gene.

GLN27GLU POLYMORPHISM IN THE Β2-ADRENORECEPTOR GENE IN PATIENTS WITH ASTHMA WITH REGARD TO THE AGE OF ONSET

Aim: The study aimed to assess the frequency of the Gln27Glu polymorphic variant in the β2-AR gene among patients with early and late-onset asthma and assess asthma risks depending on the disease phenotype. Materials and Methods: Our study included a total of 553 asthma patients who consented to participate in the study. Asthma was diagnosed according to the 2016 GINA recommendations and its later versions. The study was approved by the Bioethics Committee of the Medical Institute of Sumy State University. The analysis for determining genetic polymorphism (designated as rs1042714) was conducted through the use of polymerase chain reaction-restriction fragment length polymorphism. Statistical analysis of obtained results was performed using SPSS–17 program. Results: It was found that there is a significant difference in the distribution of alleles and genotypes in people with early-onset asthma compared to those with late-onset asthma; the statistical analysis showed a χ2 value of 41.75 and p-value of 0.001 for early-onset asthma, and a χ2 value of 44.24 and p-value of 0.001 for late-onset asthma. We did not observe a significant increase in the early-onset asthma risk with an account of different inheritance models connected to the studied polymorphism. Research that took into account the risk of late-onset asthma discovered statistically significant results regarding the dominant (p = 0.001), super-dominant (p = 0.001), and additive (p = 0.001) models of inheritance. Conclusions: Based on the data collected, it was found that individuals carrying the minor allele (both homozygotes and heterozygotes) were at a greater risk of developing asthma later in life. However, no such correlation was observed in patients with early-onset asthma.

Methylenetetrahydrofolate Reductase C677T Gene Variant in Relation to Body Mass Index and Folate Concentration in a Polish Population.

Methylenetetrahydrofolate reductase (MTHFR) is an enzyme responsible for producing an active form of folate. The MTHFR T677T genotype may have adverse health effects associated with weight gain and a reduction in folate availability. In this study, we examined the influence of the MTHFR C677T variant on BMI and determined its role as a risk factor for obesity. We also assessed the relationships between the MTHFR C677T genotype and folate and vitamin B12 concentrations in subjects before and after radical weight loss. The study group consisted of 1712 Caucasian adults of Polish nationality with a wide range of body mass indexes (BMIs). DNA was extracted from the blood, and the C677T variant was tested with RFLP-PCR and real-time-PCR. There was no significant influence found for the MTHFR 677 TT genotype on BMI or the obesity risk in codominant, dominant or recessive inheritance models. Individuals with obesity and the TT genotype had significantly lower folate concentrations. After radical weight reduction, the impact of the risk genotype, as well as homeostasis between folate and vitamin B12 in TT homozygotes, seems to be attenuated. Although the MTHFR 677TT genotype is not directly related to a higher BMI in Polish adults, it has a detrimental effect on folate concentrations in individuals with high BMI values.

Association of vitamin D levels and polymorphisms in vitamin D receptor with type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is a leading cause of death. The prevalence of T2DM in countries of the Middle East and North Africa (MENA) region, including Jordan, is among the highest worldwide. The reason(s) behind the epidemic nature of T2DM in Jordan are unknown but warrant further exploration. Studies have indicated that T2DM could be influenced by diet and/or genetic background. Evidence suggests that numerous patients with T2DM are deficient in vitamin D. The activity of vitamin D on its target tissues may be influenced by single nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR) gene. It was therefore hypothesized that SNPs in VDR could modify the risk of T2DM. To test this hypothesis, 125 patients with T2DM were recruited along with 125 controls. The study subjects were genotyped for variations in rs2228570, rs1544410, rs7975232, and rs731236 SNPs in the VDR. The levels of 25-hydroxyvitamin D [25(OH)D] were measured from the serum. The analysis revealed that reduced 25(OH)D and age were associated with the risk of T2DM (P<0.05). Moreover, under a dominant inheritance model, the GG genotype of rs2228570 was revealed to increase the risk of T2DM in univariate and multivariate analysis (P<0.05). Additionally, a chromosomal block containing the GAAG haplotype of VDR SNPs increased the risk of T2DM (OR=1.909; CI: 1.260-2.891; P=0.0021). Collectively, the present study revealed that low levels of serum 25(OH)D and rs2228570 of the VDR gene are associated with the risk of T2DM.

Single Nucleotide Polymorphisms Of Transforming Growth Factor-Β1 Gene As Potential Asthma Susceptible Variants In Punjabi Population Of Pakistan.

Candidate gene approach based on case-control model is a valuable strategy to determined disease related genetic variants. Two single nucleotide polymorphisms rs1800469 and rs2241715 in TGF β1gene have been reported to affect the asthmatic status in different populations. The main focus of this research was to find any relationship between these SNPs and asthma in Pakistani population. Using case-control model, a total of 108 individuals including 52 asthma patients and 56 healthy controls were screened to find asthma susceptibility of variants rs1800469 and rs2241715. These SNPs were genotyped using SNaPshot minisequencing assay followed by capillary electrophoresis using ABI 3130xl genetic analyzer platform. The statistical analysis of genetic data was performed by using SPSS 21, SHEsis online platform and SNPStats online web software. No association with asthma was seen in allelic model for both SNPs but genotypes analyzed under codominant, dominant, over dominant and recessive models of inheritance revealed that SNP rs2241715 is strongly associated with asthma under genotypic model. rs2241715 was found to be a genetic risk factor for asthma in Pakistani population.

A Common Variant in the CDK8 Gene Is Associated with Sporadic Pituitary Adenomas in the Portuguese Population: A Case-Control Study.

The majority of pituitary adenomas occur in a sporadic context, and in the absence of known genetic predisposition. Three common variants at the NEBL (rs2359536), PCDH15 (rs10763170) and CDK8 (rs17083838) loci were previously associated with sporadic pituitary adenomas in the Han Chinese population, but these findings have not yet been replicated in any other population. The aim of this case-control study was to assess if these variants are associated with susceptibility to sporadic pituitary adenomas in the Portuguese population. Genotype and allele frequencies were determined in 570 cases and in 546 controls. The CDK8 rs17083838 minor allele (A allele) was significantly associated with sporadic pituitary adenomas, under an additive (odds ratio (OR) 1.73, 95% confidence interval (CI) 1.19–2.50, p = 0.004) and dominant (OR 1.82, 95% CI 1.24–2.68, p = 0.002) inheritance model. The NEBL rs2359536 and PCDH15 rs10763170 variants were not associated with the overall risk for the disease, although a borderline significant association was observed between the PCDH15 rs10763170 minor allele (T allele) and somatotrophinomas (dominant model, OR 1.55, 95% CI 1.02–2.35, p = 0.035). These findings suggest that the CDK8 rs17083838 variant, and possibly the PCDH15 rs10763170 variant, may increase susceptibility to sporadic pituitary adenomas in the Portuguese population.

Common variant c.-22 + 155C > T of BDNF as a genetic risk factor of opium addiction

Opioid use disorder is largely genetic in nature. The common genetic variants present in population might be modulating the risk by affecting expression level of genes in the brain. Here, we study common variants in promoter region of brain-derived neurotrophic factor (BDNF) and Dopamine receptor D2 (DRD2) in a highly prevalent opium addiction geographical region. We identify highly expressed isoforms using CAGE datasets and its associated promoter. Common variants were extracted from promoters and genotyped in addicts compared to controls. The associated variants obtained through hitchhiking events were removed and eQTL analysis was performed. We identified two mutations (rs7944119:G > T and rs13306221:C > T) in the promoter of BDNF to be significantly associated with the addiction. In the dominant inheritance model, both rs7944119 and rs13306221 increases the risk of addiction. Of these two, rs7944119 was in linkage disequilibrium with rs13306221 and showed association due to hitchhiking. The rs13306221-T was associated with a lower expression level of the short BDNF isoform in the Cerebellar cortex. This finding suggests that rs13306221 (c.-22 + 155C > T) could increase risk of addiction by decreasing the expression level of the short isoform of BDNF, therefore, changes in the expression of the BDNF might not be the effect, but rather a cause of opium addiction disorder. Or, subjects with less expression of BDNF are more prone to addiction and addiction further decreases expression of BDNF short isoform in the brain. Although, it should be explored further in more detail.

The Impact of CYP3A5, CYP1A1, GSTM1, GSTT1, GSTP1 and TPMT Gene Polymorphisms on the Risk of Chronic Myeloid Leukemia

Polymorphisms in the genes encoding drug metabolising enzymes (DME) cause inter-individual variations in metabolising exogenous and endogenous substances, which has been related to the risk of various diseases. The present study was conducted to investigate the association of CYP1A1, GSTM1, GSTT1, GSTP1 and CYP3A5 and TPMT gene polymorphisms with susceptibility to chronic myeloid leukemia (CML). 89 samples of CML patients and 135 control samples were included in this study. Genotyping of CYP1A1, GSTM1, GSTT1, GSTP1 and CYP3A5 and TPMT gene polymorphisms was performed by a Polymerase chain reaction-Restriction fragment length polymorphism (PCR-RFLP). The frequency of GSTM1 null genotype was found to be significantly higher among chronic myeloid leukemia (CML) patients vs controls (39% vs 18.5%, respectively) with a 2.85-fold increased risk for CML. The frequency of GSTT1 null was found to be significantly lower in CML patients vs controls (26% vs 40.7%). Under the dominant inheritance model, GSTP1 gene polymorphism was significantly associated with reduced risk of CML. Moreover, CYP3A5 * 6 and TPMT * 2 alleles were absent among CML patients and the control group. GSTM1 null genotype was found to be associated with an increased risk of CML whereas TPMT * 2 and CYP3A5 * 6 alleles were absent in the population of Punjab.

A meta-analysis of the association of ApaI, BsmI, FokI, and TaqI polymorphisms in the vitamin D receptor gene with the risk of polycystic ovary syndrome in the Eastern Mediterranean Regional Office population.

BackgroundThe results of case-control studies on the association between vitamin D receptor gene (VDR) polymorphisms and polycystic ovary syndrome (PCOS) are inconclusive.ObjectiveWe aimed to more precisely evaluate the correlation between the ApaI, BsmI, FokI, and TaqI VDR gene polymorphisms and PCOS susceptibility.Materials and MethodsPubMed, Scopus, Science Citation Index, and Google Scholar databases were searched to retrieve related reports released up to the end of 2020. To evaluate the association strength of the VDR gene polymorphisms with PCOS risk, pooled odds ratios (OR) with a 95% confidence interval were determined.ResultsIn total, 1,119 subjects (560 PCOS cases and 559 controls) from 7 studies were included which met the inclusion criteria. A statistically significant association between the TaqI polymorphism and PCOS susceptibility was found in the Eastern Mediterranean Regional Office population (T vs. t: OR = 0.715; TT vs. tt: OR = 0.435, p 0.001; TT vs. Tt+tt: OR = 0.696, p = 0.01; tt vs. TT+Tt: OR = 1.791, p 0.001). It was found that the ApaI variant was a risk factor in the dominant inheritance model (AA vs. Aa+aa: OR = 1.466, p = 0.01) and the FokI polymorphism was a protective factor in the recessive inheritance model (ff vs. FF+Ff: OR = 0.669, p = 0.04). The VDR BsmI polymorphism did not show association with PCOS susceptibility.ConclusionOur meta-analysis revealed that the VDR ApaI in the dominant model, VDR FokI in the recessive model, and VDR TaqI polymorphisms in all genetic models are associated with vulnerability to PCOS. However, further studies with a larger sample size are required.

Identification of Genetic Variations in the NAD-Related Pathways for Patients with Major Depressive Disorder: A Case-Control Study in Taiwan.

Background and Objectives: Nicotinamide adenine dinucleotide (NAD) is an important coenzyme in various physiological processes, including sirtuins (SIRTs) and kynurenine pathway (KP). Previous studies have shown that lower NAD levels can be indicative of increased risks of cancer and psychiatric disorders. However, there has been no prior study exploring the link between NAD homeostasis and psychiatric disorders from a genetic perspective. Therefore, we aimed to investigate the association of genetic polymorphism in the pathways of NAD biosynthesis with major depressive disorder (MDD). Methods: A total of 317 patients were included in the case group and were compared with sex-matched control group of 1268 participants (1:4 ratio) from Taiwan Biobank (TWB). All subjects in the control group were over 65 years old, which is well past the average age of onset of MDD. Genomic DNA extracted from patients’ blood buffy coat was analyzed using the Affymetrix TWB array. Full-model tests were conducted for the analysis of single nucleotide polymorphism (SNPs) in all candidate genes. We focused on genes within the NAD-related candidate pathways, including 15 in KP, 12 in nicotinate metabolism, 7 in SIRTs, and 19 in aldehyde dehydrogenases (ALDHs). A total of 508 SNPs were analyzed in this study. After significant SNPs were determined, 5000 genome-wide max(T) permutations were performed in Plink. Finally, we built a predictive model with logistic regression and assessed the interactions of SNPs with the haplotype association tests. Results: We found three SNPs that were significantly associated with MDD in our NAD-related candidate pathways, one within the KP (rs12622574 in ACMSD) and two within the nicotinate metabolism (rs28532698 in BST1 and rs3733593 in CD38). The observed association with MDD was significant in the dominant model of inheritance with marital status, education level, and body mass index (BMI) adjusted as covariates. Lastly, in haplotype analysis, the three associated SNPs consisted of one haploblock in ACMSD, four haploblocks in BST1, and two haploblocks in CD38. Conclusions: This study provides the first evidence that genetic variations involved in NAD homeostasis in the KP and nicotinate metabolism may be associated with the occurrence of MDD.

Clinical Utility of Amplification Refractory Mutation System-Based PCR and Mutation-Specific PCR for Precise and Rapid Genotyping of Angiotensin-Converting Enzyme 1 (ACE1-rs4646996 D>I) and Angiotensin-Converting Enzyme 2 (ACE2-rs4240157T>C) Gene Variations in Coronary Artery Disease and Their Strong Association with Its Disease Susceptibility and Progression

Background: Experimental clinical and research studies demonstrated that the renin–angiotensin system (RAS) affects the pathogenesis of atherosclerosis and the prognosis of coronary heart disease (CHD). The results show that ACE2 (angiotensin I-converting enzyme 2) might act as a protective protein for cardiovascular diseases; however, only a few studies in human populations have been carried out. The aim of this study was to develop, optimize, and validate a direct T-ARMS-based PCR assay for the precise and rapid genotyping of ACE1-rs4646996 D>I and ACE2-rs4240157T>C and study their association with coronary artery disease susceptibility and progression. Methodology: This study included 149 consecutive coronary artery disease patients and 150 healthy controls. We utilized T-ARMS for the precise and rapid genotyping of ACE2-rs4240157; rs4646994. Results: Our results indicated that the ACE1-rs4646996 D>I genotypes observed between CAD cases and controls were statistically significant (p < 0.008) and, similarly, the ACE2-rs4240157T>C genotypes observed were significant (p < 0.0001). Moreover, the frequency of the D allele (ACE1-D>I) and C allele (ACE2-rs4240157T>C) was found to be higher among CAD patients than the HC. Our results indicated that in the codominant model, the ACE2-ID genotype was strongly associated with increased CAD susceptibility in a codominant model with an OR of 2.37, (95%) CI = (1.023–5.504), and p < 0.04. Similarly, the ACE2-DD genotype was strongly associated with an increased CAD susceptibility with an OR of 3.48, (95%) CI = (1.49 to 8.117), and p < 0.003. Similarly, in allelic comparison, the D allele was strongly associated with CAD susceptibility with an OR of 1.59, (95%) CI = (1.12–2.24), and p < 0.003. Our results revealed that there was a significant correlation between ACE2-I/D genotypes and hypertension, T2D, and obesity (p < 0.05). The results of ACE2 rs4240157 genotyping indicated a strong association in the codominant model with an increased CAD susceptibility with an OR of 3.62, (95%) CI = (2.027 to 6.481), and p < 0.0001. Similarly, in a dominant inheritance model, a strong association is observed between the ACE2 rs4240157 (CT+CC) genotype with an OR of 6.34, (95%) CI = (3.741 to 10.749), and p < 0.0001. In allelic comparison, the T allele was strongly associated with CAD susceptibility with an OR of 5.56, (95% CI = (3.56 to 7.17), and p < 0.0001. Similarly, our results revealed that there was a significant association of the ACE2-rs4240157T>C genotypes with Triglycerides (mg/dL), HDL-C (mg/dL), total Cholesterol (mg/dL), and C-reactive protein (mg/L) in CAD. Conclusion: It was indicated that the ARMS technique and MS-PCR assay proved to be fast, accurate, and reliable for ACE2-rs4240157T>C and ACE1-rs4646996 D>I, respectively, and can be used as a potential molecular tool in the diagnosis of genetic diseases in undeveloped and developing countries—where there might be a shortage of medical resources and supplies. ACE1-I>D genotypes were strongly associated with T2D, hypertension, and obesity (p < 0.002). Besides the ACE2-rs4240157 CT heterozygosity genotype, the T allele was strongly associated with CAD susceptibility. Future longitudinal studies in different ethnic populations with larger sample sizes are recommended to validate these findings

TP53 Mutant Versus Wild-Type Zebrafish Larvae Under Starvation Stress: Larvae Can Live Up to 17 Days Post-Fertilization Without Food.

In this study, an experimental protocol has been developed for comparing survival rates of mutant and wild-type zebrafish larvae under extreme starvation. Zebrafish larvae were placed in 96-well plates at fourth day postfertilization (dpf) and larvae were not fed at all from hatching to cease. Zdf1 zebrafish line was used, a strain carrying the (cancer) pathogenic TP53-M214K amino acid substitution. TP53-M214 corresponds to the human TP53-M246 and both residues are located on the DNA-binding domain of the p53 protein. Survival statistical analysis did not show any significant difference in the overall survival rates between homozygous mutant and wild-type larvae. When considering 15 dpf as the endpoint of the experiment (66% of larvae died), a borderline statistical significance was observed for the dominant model of inheritance (p = 0.015; relative hazard = 0.8320). Despite the fact yolk sac of larvae is depleted at 7-8 dpf, 34% of larvae survive until 15 dpf and 1.5% until 17 dpf. Concluding, three main results derive from this study: (1) pathogenic homozygous mutations in TP53 probably do not alter survival rates of zebrafish larvae under starvation; (2) zebrafish larvae can live up to 17 dpf without food, surviving only with their initial nutritional supplies; and (3) an easy and affordable protocol has been developed for estimating survival rates of zebrafish larvae under stressful conditions.

Association of selected polymorphisms in GPX4, COMT, pre-miR-125a, pre-miR-10a, and pre-miR-323b genes in Iranian women with idiopathic recurrent pregnancy loss: A case-control study.

BackgroundRecurrent pregnancy loss (RPL) is a major concern among women worldwide. However, the exact mechanisms underlying miscarriage are not well understood. Recent evidence suggests that single nucleotide polymorphisms in various genes, especially miRNAs, may be responsible for RPL.ObjectiveWe surveyed the association between polymorphisms in pre-miR-125a, pre-miR-10a, pre-miR-323b, GPX4, and GPX4 in Iranian women with idiopathic RPL.Materials and MethodsDNA was extracted from blood samples of 116 women with idiopathic RPL and 89 healthy women as controls who had previously had at least two successful pregnancies. Polymerase chain reaction was used for the amplification of the genes. Genotype screening along with SNaPshot were performed to detect different polymorphisms. Finally, the polymorphisms and frequency of each genotype were compared between the two groups.ResultsThe frequencies of polymorphisms in pre-miR-125a (p 0.001) and pre-miR-10a (p = 0.04) were calculated among the case and control groups, which showed a statistical difference (p 0.05), indicating an association between these polymorphisms and the symptoms of RPL. The frequencies of polymorphisms of genotypes in GPX4, COMT and pre-miR-323b did not demonstrate any difference between the two groups. Also, the amount of alleles in pre-miR-125a and pre-miR-10a were significantly different (p 0.001 and p = 0.02, respectively) and the dominant inheritance model was proposed.ConclusionIn conclusion, pre-miR-125a and pre-miR-10a can be associated with RPL in women. The SNaPshot technique is a valuable tool to evaluate possible associations between polymorphisms and health conditions.

A new aspect on the correlation of ten SNPs in MIR and their target genes in dopaminergic pathways in schizophrenia

BackgroundSchizophrenia (SCZ) is a severe mental disorder in which people interpret reality abnormally. Different studies indicated a complex polygenic control over SCZ. In the present study, we investigated the potential correlation between ten SNPs among MicroRNA (MIR) and their target genes; rs369770942, rs143525573, rs200982455, rs530404895, rs753764536, rs374732351, rs4680, rs165599, rs340597269, and rs10759, and schizophrenia in the Iranian population.ResultsThe results revealed that the T allele in rs200982455 increased the risk factor by 3.19 times. We obtained a significant association between rs165599 and schizophrenia in codominant, dominant, and overdominant inheritance models (P = 0.016, P = 0.01, P = 0.004, respectively). Moreover, the risk of schizophrenia increased in the presence of the G allele in rs165599 up to 2.12, 2.35, and 2.28 times, respectively. The A allele in rs10759 increased the risk factor up to 1.05 times.ConclusionOur finding showed that some of the studied SNPs within the genes and MIRs involved in the dopaminergic pathway may consider as a biomarker in the diagnostic patterns in Schizophrenia.

Common variants in AGR1 genes contributed to the risk and traits of cirrhotic cardiomyopathy in the Han Chinese population.

Aim: This study aimed to determine the association between polymorphisms of the ARG1 gene and the risk and traits of cirrhotic cardiomyopathy (CCM). Methods: A total of 468 CCM and 1012 cirrhosis patients were enrolled, and 12 single-nucleotide polymorphisms (SNPs) in the ARG1 gene were genotyped. Differences in genotype, allele and haplotype frequencies of the SNPs between the CCM and cirrhosis groups were analyzed by chi-square test. Correlations of the genotypes of SNPs and representative traits of liver and heart function were performed using linear regression analysis. Results: SNPs rs2781666 and rs2781667 were associated with the risk of CCM in both dominant and additive inheritance models. The GG genotype frequency of rs2781666 and CC genotype frequency of rs2781667 were lower in the CCM group than in the cirrhosis group. The G-C haplotype frequency of the block consisting of rs2781666 and rs2781667 was higher and the T-T haplotype frequency was lower in CCM patients than in cirrhosis patients. SNP rs2781666 was associated with the alanine transaminase level, and rs2781667 was associated with the ARG1 level and left atrial diameter. Conclusion: SNPs rs2781666 and rs2781667 in the ARG1 gene were associated with susceptibility to and traits of CCM in the Han Chinese population.

The Relationship between Cadherin Polymorphisms and the Risk of Delayed Encephalopathy after Acute Carbon Monoxide Poisoning in the Chinese Han Population.

Objective The purpose of this study was to analyze the relationship between cadherin gene single-nucleotide polymorphisms (SNPs) and the risk of delayed encephalopathy after acute carbon monoxide poisoning (DEACMP). Materials and Methods A total of 416 patients with DEACMP and 754 patients with acute carbon monoxide poisoning (ACMP) were recruited. We used the Sequenom MassARRAY® system to detect cadherin gene SNPs related to DEACMP. Using different genetic analysis models, we evaluated the relationship between the cadherin gene polymorphisms and risk of DEACMP. Results We found that rs1944294 in the N-cadherin (CDH2) gene showed significant differences in genotype frequencies between the two groups under codominant and dominant inheritance models. Similarly, rs2513796 in the cadherin-17 (CDH17) gene showed significant differences under the codominant, dominant, and overdominant genetic models. And the T allele frequency of rs1944294 in the DEACMP group was significantly higher than that in the ACMP group (P = 0.023). Conclusions Cadherin gene SNPs (rs1944294, rs2513796) are associated with an increased risk of DEACMP in the Chinese population.

The influence of host genetics on liver microbiome composition in patients with NAFLD

SummaryBackgroundHuman body microbiotas are influenced by several factors, including the interaction of the host with the environment and dietary preferences. The role of host genetics in modulating the liver microbiota in the context of NAFLD remains unknown. To address this gap, we examined the interplay between the liver metataxonomic profile and host genetics.MethodsWe obtained 16S rRNA gene sequences from liver biopsies and genotypes by Taqman-assays in 116 individuals. We compared taxon abundance at the genus level across host genotypes using dominant models of inheritance. We focused the analysis on variants influencing the risk/ protection against NAFLD-histological severity (PNPLA3-rs738409, TM6SF2-rs58542926, MBOAT7-rs641738, and HSD17B13-rs72613567) and a variant influencing macronutrient intake (FGF21-rs838133). We also explored the variants' combined effect via a polygenic risk score (PRS).FindingsWe identified at least 18 bacterial taxa associated with variants in the selected loci. Members of the Gammaproteobacteria class were significantly enriched in carriers of the rs738409 and rs58542926 risk-alleles, including Enterobacter (fold change [FC]=6.2) and Pseudoalteromonas (FC=2) genera, respectively. Lawsonella (1.6-FC), Prevotella_9 (FC=1.5), and Staphylococcus (FC=1.3) genera were enriched in rs838133-minor allele carriers, which is linked to sugar consumption and carbohydrate intake. Tyzzerella abundance (FC=2.64) exhibited the strongest association (p = 0.0019) with high PRS values (>4 risk alleles). The percentage of genus-level taxa variation explained by the PRS was ∼7.4%, independently of liver steatosis score and obesity.InterpretationWe provided evidence that genetic variation may influence the liver microbial DNA composition. These observations may represent potentially actionable mechanisms of disease.

One‐carbon metabolism pathway genes and their non‐association with the development of amyotrophic lateral sclerosis

Although of unknown etiology, some mechanisms associated with the metabolic cycle of folate are speculated to be related to the genesis of amyotrophic lateral sclerosis (ALS). Thus, the aim of the study was to analyze the role of genetic polymorphisms rs1051266 in SLC19A1 gene and rs1805087 in MTR gene and their associations with ALS development. A case-control study was conducted with 101 individuals with ALS and 119 individuals without diagnosis of neurodegenerative diseases, from the Brazilian central population. The polymorphisms were determined using the polymerase chain reaction-restriction fragment length polymorphism technique. The results showed no statistically significant differences, even when genotypes were analyzed by the dominant, recessive, codominant, and overdominant inheritance models. It was observed a statistical significance relating alcohol consumption with individuals in the case group (p = 0.01). Therefore, the need for more studies to evaluate the influence of genetic variants is highlighted, seeking to provide information on the etiopathogenesis of ALS.

Ectonucleotide pyrophosphatase/phosphodiesterase 1 (K121Q rs1044498) polymorphism is associated with diabetic nephropathy but not obesity among type-2 diabetes mellitus Egyptian patients

IntroductionGenetics contribute to the development of type-2 diabetes mellitus (T2DM), its complications, and phenotypes such as diabetic nephropathy (DN) and obesity. Although the likely associations among the ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) gene, DN and obesity have been massively investigated, the results are still controversial. This study aimed to assess whether ENPP1 K121Q (A/C rs1044498) variant is associated with DN and obesity in T2DM Egyptian patients. We genotyped this variant in a total of 183 T2DM Egyptian patients who were classified into cases (91 participants with moderately increased albuminuria or severely increased albuminuria ≥ 30 mg/g) and controls (92 patients with normoalbuminuria <30 mg/g) using TaqMan technology.ResultsPatients, with the C (minor/risk) allele, had significantly higher moderately increased albuminuria/severely increased albuminuria levels (P < 0.001) and albumin-to-creatinine ratio (P = 0.001) than those with the wild A allele. AC and CC genotypes of ENPP1 K121Q (A/C, rs1044498) variant and its C-allele frequencies are significantly higher in cases than controls (P = 0.043 and 0.013), respectively, and in patients with estimated glomerular-filtration rate (eGFR) less than 60 than those with eGFR more than 60 (P = 0.014 and 0.004), respectively. AC and CC genotypes are associated with cases with a significant odds ratio in both dominant [odds ratio (OR): 2.003, 95% confidence interval (CI): 1.106–3.628, P = 0.022) and additive (OR: 1.865, 95% CI: 1.134–3.070, P = 0.014) models of inheritance and in patients with eGFR less than 60 in the dominant model of inheritance (OR: 2.398, 95% CI: 1.258–4.571, P = 0.008), but showed no association with obesity (P > 0.05).ConclusionENPP1 K121Q (A/C, rs1044498) variant is associated with DN but not obesity among Egyptian T2DM patients.

Association of interleukin-17A gene promoter polymorphism with the susceptibility to generalized chronic periodontitis in an Iranian population

Chronic periodontitis (CP) is characterized by an immune response, leading to the destruction of periodontal supporting tissue. The effect of inflammatory and genetic factors on periodontitis has been evaluated previously. The interleukin (IL-17) as an inflammation regulator seems to play a critical role in periodontitis pathogenesis. Here, in the current study, we aimed to investigate the association of -197 G > A (rs2275913) IL-17 gene promoter polymorphism with generalized severe CP in an Iranian population. In this case-control study, a total of 54 patients with periodontitis and 118 normals were enrolled. The polymerase chain reaction-restriction fragment length polymorphism technique was applied to detect IL-17 promoter rs2275913 genotypes in association with the susceptibility to severe CP. Chi-square test or Fisher's exact test was employed to compare genotype frequencies between groups. P < 0.05 were considered statistically significant. The distribution of genotypes and alleles was in Hardy-Weinberg equilibrium. Although no significant association was observed between the risk of periodontitis and genotype frequencies under any of the inheritance models, the GG genotype was higher in healthy controls, while the AG genotype was more frequently observed in patients under the codominant model ([odd ratio [OR] = 2.14, 95% confidence interval (CI) (1.01-4.53), P = 0.13]). The frequency of AG-AA genotype was higher in patients under dominant inheritance model ([OR = 1.92, 95% CI (0.94-3.93), P = 0.068]), while GG-AA and AG genotypes were higher in healthy controls under over dominant model (OR = 0.1.95, 95% CI [0.98-3.86], P = 0.055). The results of this study showed that the presence of allele A and AG genotypes could be considered possible factors in increasing the risk of developing CP, although the differences of allele and genotype frequencies were remarkable but not statistically significant between the two groups.