Genetic predisposition of BDNF (rs6265) gene is susceptible to Schizophrenia: A prospective study and updated meta-analysis / Asociación entre el gen BDNF (rs6265) y predisposición a la esquizofrenia: estudio prospectivo y metaanálisis actualizado

Introduction: Genetic polymorphism in the BDNF gene has been found to cause neuronal alterations and has been identified as a causal factor for many neuropsychiatric disorders. Therefore, various neurological case–control studies and meta-analyses have been conducted to find the possible link between BDNF and susceptibility to schizophrenia. Method: This meta-analysis gathered data from 25 case–control studies including a total of 8384 patients with schizophrenia and 8821 controls in order to identify the relationship between the rs6265 single nucleotide polymorphism and the disease, evaluating the combined odds ratio and 95% confidence intervals under 5 different genetic models. Validation followed the “Leave one out” method, and we used the Egger test and Begg's funnel plot to identify publication bias. Results: Research into the rs6265 (G/A) polymorphism revealed a non-significant association with schizophrenia in all 5 genetic models; in the subgroup analysis, no association was found between white and Asian populations, with a p value > .05. Conclusions: Overall, the updated meta-analysis revealed that rs6265 exonic polymorphisms do not increase susceptibility to this disease. However, to better understand the pathogenesis of the disease, there is a need for further case–control studies into the BDNF polymorphism including larger sample sizes and different ethnic groups.(AU)

Introducción: Se sabe que los polimorfismos del gen BDNF provocan alteraciones neuronales y parecen ser un factor causal en muchos trastornos neuropsiquiátricos. Es por ello que se han llevado a cabo varios metaanálisis y estudios de casos y controles con el objetivo de evaluar la posible relación entre BDNF y la esquizofrenia. Método: Realizamos un metaanálisis de 25 estudios de casos y controles, que incluyó un total de 8.384 pacientes con esquizofrenia y 8.821 controles. Se analizó la relación entre el polimorfismo de nucleótido simple rs6265 y la esquizofrenia mediante odds ratios combinados y sus intervalos de confianza del 95% con 5 modelos genéticos diferentes. Utilizamos el método de validación cruzada dejando uno fuera («leave one out»), la prueba de Egger y el gráfico en embudo de Begg para identificar posibles sesgos de publicación. Resultados: Los estudios sobre el polimorfismo rs6265 (G/A) muestran una asociación no significativa con la esquizofrenia en los 5 modelos genéticos. En el análisis por subgrupos, no se encontró relación con las poblaciones caucásica y asiática (p > 0,05). Conclusiones: La presencia de polimorfismos rs6265 no aumenta la predisposición a desarrollar esquizofrenia. Sin embargo, se deben realizar más estudios de casos y controles sobre polimorfismos de BDNF, con muestras más numerosas y con individuos de diferentes grupos étnicos, para comprender mejor los mecanismos patogénicos de la enfermedad.(AU)

Genetic predisposition of BDNF (rs6265) gene is susceptible to Schizophrenia: A prospective study and updated meta-analysis.

INTRODUCTION: Genetic polymorphism in the BDNF gene has been found to cause neuronal alterations and has been identified as a causal factor for many neuropsychiatric disorders. Therefore, various neurological case-control studies and meta-analyses have been conducted to find the possible link between BDNF and susceptibility to schizophrenia. METHOD: This meta-analysis gathered data from 25 case-control studies including a total of 8384 patients with schizophrenia and 8821 controls in order to identify the relationship between the rs6265 single nucleotide polymorphism and the disease, evaluating the combined odds ratio and 95% confidence intervals under 5 different genetic models. Validation followed the "Leave one out" method, and we used the Egger test and Begg's funnel plot to identify publication bias. RESULTS: Research into the rs6265 (G/A) polymorphism revealed a non-significant association with schizophrenia in all 5 genetic models; in the subgroup analysis, no association was found between white and Asian populations, with a p value>.05. CONCLUSIONS: Overall, the updated meta-analysis revealed that rs6265 exonic polymorphisms do not increase susceptibility to this disease. However, to better understand the pathogenesis of the disease, there is a need for further case-control studies into the BDNF polymorphism including larger sample sizes and different ethnic groups.

[Association of polymorphisms in SEC16B, DNAJC27, FTO and MC4R genes with overweight and obesity in Han preschool children].

OBJECTIVE: To investigate the association of polymorphisms in SEC16B rs633715, DNAJC27 rs713586, FTO rs11642015 and MC4R rs6567160 with overweight and obesity in Han Chinese preschool children. METHODS: A total of 749 Han Chinese preschool children from Henan and Guizhou Province of Long-term Health Effects Assessment Project of Infants and Toddlers Nutritional Pack were selected for the study and divided into an overweight and obese group and a normal control group in 2022. rs633715, rs713586, rs11642015 and rs6567160 were genotyped using Kompetitive allele-specific PCR(KASP) technology. The distribution of genotypic polymorphisms was compared using the χ~2 test. The association between the four loci and overweight and obesity in preschool children was analyzed using a multifactorial logistic regression model. RESULTS: The statistical analysis revealed a significant disparity(P<0.05) in the distribution of genotypic polymorphisms of rs633715 and rs6567160 among preschoolers in Henan and Guizhou Province. CC heterozygous mutant and recessive models at rs633715 locus were associated with susceptibility to overweight and obesity in preschool children [OR and 95% CI 2.915(1.163-7.305), and 2.997(1.226-7.323), respectively, both P<0.05]. TC heterozygous mutant and dominant models at rs713586 locus were also associated susceptibility to overweight and obesity in preschool children(OR and 95% CI were 2.362(1.054-5.289)and 2.362(1.054-5.289), respectively, both P<0.05). rs11642015 and rs6567160 loci were not associated with susceptibility to overweight and obesity in preschool children(P>0.05). The result of the analysis of the cumulative effect of rs633715 and rs713586 showed that the number of genotypes carrying the risk genotype was positively associated with the risk of overweight and obesity in preschool children(P_(trend)<0.01). CONCLUSION: Among Han Chinese preschool children, SEC16B rs633715 and DNAJC27 rs713586 were associated with susceptibility to overweight and obesity in preschool children. Moreover, rs633715 and rs713586 had a cumulative effect on susceptibility to overweight and obesity in preschool children, the number of risk genotypes carried was positively associated with childhood overweight and obesity risk.

Assessment of TNF-α (-857 C/T) gene polymorphism in oral lichen planus disease: A case-control study.

Background and aims: Oral lichen planus (OLP) is an inflammatory mucocutaneous disorder with an immune-mediated pathogenesis. The tumor necrosis factor-α (TNF-α) level in the serum of OLP patients is significantly higher than in the control group. TNF-α-857 C/T polymorphism can be related to the increased TNF-α level in blood circulation. This study investigated the relationship between TNF-α (-857 C/T) polymorphism and OLP patients in an Iranian population. Methods: Saliva samples were taken from 200 people, including 100 patients with OLP and 100 healthy people who did not have significant differences in age and sex. Then, DNA was extracted from them and the TNF-α (-857 C/T) genotype was identified using the polymerase chain reaction with confronting two-pair primers method. Statistical Package for the Social Sciences version 16 software analyzed the results. Results: The frequency of C/C, C/T, and T/T genotypes of the TNF-α-857 C/T polymorphism in the patient group were 78%, 18%, and 4%, respectively, and in the control group were 72%, 23%, and 5%, respectively. The differences between the two groups regarding allele (χ 2 = 0.97, p = 0.32) and genotype (χ 2 = 0.96, p = 0.62) frequency among the studied population were insignificant. Conclusion: This study showed that the difference in the frequency of single nucleotide polymorphism TNF-α-857 C/T polymorphism in the patient and control group had no significant relationship with the increased OLP incidence. Also, no significant association was observed between allele and genotype frequency of TNF-α (-857 C/T) with OLP subtypes.

Systematical explorations of forensic feature and population genetic diversity of the Chinese Mongolian group from northwest China via a self-constructed Multi-InDel panel.

This study aimed to investigate the genetic polymorphisms and population characteristics of Chinese Mongolian group from northwest China (NCM) through a self-developed panel including 43 autosomal insertion/deletion (A-InDel) polymorphism genetic markers. Herein, 288 unrelated healthy individuals from the NCM group were employed to obtain the genetic data of 43 A-InDels through multiplex PCR amplification and InDel genotyping using capillary electrophoresis platform. In addition, multiplex population genetic analyses were performed between the NCM group and 27 reference populations. There were no deviations at 43 loci from Hardy-Weinberg equilibrium in the NCM group. The observed heterozygosity (Ho) values ranged from 0.312 8 to 0.559 2, and the combined power of discrimination (CPD) and cumulative probability of exclusion (CPE) values in the NCM group were 0.999 999 999 999 999 998 77 and 0.999 814, respectively. The forensic parameter values indicated that this panel was polymorphic and informative in the NCM group and could be used as an effective tool for forensic personal identification. Furthermore, the results of pairwise genetic distances, principal component analysis, multidimensional scaling analysis, phylogenetic tree construction, and admixture analysis among the NCM group and 27 reference populations revealed that there were closer genetic relationships between the NCM group and East Asian populations, especially Chinese Hui group (CHH) from the northwest China, which is consistent with the geographical location. These present findings contributed to the ongoing genetic explorations and insights into the genetic architecture of the NCM group.

6Pgdh polymorphism in wild bulb mite populations: prevalence, environmental correlates and life history trade-offs.

Genetic polymorphism in key metabolic genes plays a pivotal role in shaping phenotypes and adapting to varying environments. Polymorphism in the metabolic gene 6-phosphogluconate dehydrogenase (6Pgdh) in bulb mites, Rhizoglyphus robini is characterized by two alleles, S and F, that differ by a single amino acid substitution and correlate with male reproductive fitness. The S-bearing males demonstrate a reproductive advantage. Although the S allele rapidly fixes in laboratory settings, the persistence of polymorphic populations in the wild is noteworthy. This study examines the prevalence and stability of 6Pgdh polymorphism in natural populations across Poland, investigating potential environmental influences and seasonal variations. We found widespread 6Pgdh polymorphism in natural populations, with allele frequencies varying across locations and sampling dates but without clear geographical or seasonal clines. This widespread polymorphism and spatio-temporal variability may be attributed to population demography and gene flow between local populations. We found some correlation between soil properties, particularly cation content (Na, K, Ca, and Mg) and 6Pgdh allele frequencies, showcasing the connection between mite physiology and soil characteristics and highlighting the presence of environment-dependent balancing selection. We conducted experimental fitness assays to determine whether the allele providing the advantage in male-male competition has antagonistic effects on life-history traits and if these effects are temperature-dependent. We found that temperature does not differentially influence development time or juvenile survival in different 6Pgdh genotypes. This study reveals the relationship between genetic variation, environmental factors, and reproductive fitness in natural bulb mite populations, shedding light on the dynamic mechanisms governing 6Pgdh polymorphism.

BRAF and RET polymorphism association with thyroid cancer risk, a preliminary study from Khyber Pakhtunkhwa population.

BACKGROUND: Thyroid cancer, originating in the neck's thyroid gland, encompasses various types. Genetic mutations, particularly in BRAF and RET genes are crucial in its development. This study investigates the association between BRAF (rs113488022) and RET (rs77709286) polymorphisms and thyroid cancer risk in the Khyber Pakhtunkhwa (KP) population. METHODS: Blood samples from 100 thyroid cancer patients and 100 healthy controls were genotyped using ARMS-PCR followed by gel electrophoresis and statistical analysis. RESULTS: Analysis revealed a significant association between the minor allele T of BRAF (rs113488022) and thyroid cancer risk (P = 0.0001). Both genotypes of BRAF (rs113488022) showed significant associations with thyroid cancer risk (AT; P = 0.0012 and TT; P = 0.045). Conversely, the minor allele G of RET (rs77709286) exhibited a non-significant association with thyroid cancer risk (P = 0.2614), and neither genotype showed significant associations (CG; P = 0.317, GG; P = 0.651). Demographic and clinical parameters analysis using SPSS showed a non-significant association between BRAF and RET variants and age group (P = 0.878 and P = 0.536), gender (P = 0.587 and P = 0.21), tumor size (P = 0.796 and P = 0.765), or tumor localization (P = 0.689 and P = 0.727). CONCLUSION: In conclusion, this study emphasizes the significant association between BRAF polymorphism and thyroid cancer risk, while RET polymorphism showed a less pronounced impact. Further validation using larger and specific datasets is essential to establish conclusive results.

The role of genetic polymorphisms for inducing genotoxicity in workers occupationally exposed to benzene: a systematic review.

Benzene is used worldwide as a major raw material in a number of industrial processes and also a potent airborne pollutant emitted from traffic exhaust fume. The present systematic review aimed to identify potential associations between genetic polymorphisms and occupational benzene-induced genotoxicity. For this purpose, a total of 22 selected studies were carefully analysed. Our results revealed a positive relation between gene polymorphism and genotoxicity in individuals exposed to benzene, since 17 studies (out of 22) observed positive relations between genotoxicity and polymorphisms in xenobiotics metabolizing genes influencing, therefore, individuals' susceptibility to genomic damage induced by benzene. In other words, individuals with some genotypes may show increase or decrease DNA damage and/or higher or lower DNA-repair potential. As for the quality assessment, 17 studies (out of 22) were categorized as Strong or Moderate and, therefore, we consider our findings to be trustworthy. Taken together, such findings are consistent with the notion that benzene induces genotoxicity in mammalian cells being strongly dependent on the genetic polymorphism. Certainly, such findings are important for clarifying the role of biomarkers related to genotoxicity in human biomonitoring studies.

Blood and tissue levels of persistent organic pollutants and genetic susceptibility in patients with breast cancer.

We investigated possible associations between the internal concentrations of POPs and correlations between blood and tumor tissue concentrations in patients who underwent surgery for breast cancer and breast reduction as controls. Genetic variations in CYP1A1, GSTP1, GSTM1, and GSTT1 and hOGG1 were evaluated to determine whether they represent risk factors for breast cancer. Certain POPs have been found to be associated with breast cancer development. GST-P1 polymorphism represented a significant risk for breast cancer with unadjusted OR. However, the GSTT1 null polymorphism represented a significant risk for breast cancer when OR adjusted for age and smoking status. CYP1A1 polymorphism was a significant risk factor for breast cancer, regardless of whether the OR was adjusted. These results suggest that exposure to certain POPs, GSTT1 and CYP1A1 polymorphisms, age, and smoking status are risk factors for breast cancer. In addition, the blood concentrations of some POPs represent surrogates for breast tissue concentrations.

Nomogram developed with APOA5 genetic variant rs662799 and clinical characteristics predicting risk of essential hypertension in a Chinese population.

Background: The apolipoprotein A5 (APOA5) gene has been identified as a key regulatory factor in triglyceride (TG) metabolism and plasma lipid levels. Genetic polymorphisms of APOA5 have been linked to an elevated risk of atherosclerosis, metabolic syndrome, stroke, and coronary artery disease. The rs662799 variant is a single nucleotide polymorphism (SNP) that occurs at a specific position within the APOA5 gene. However, the association between rs662799 polymorphism and essential hypertension (EHT) remains unclear. The study aimed to comprehensively examine the potential correlation between the rs662799 polymorphism and the susceptibility to EHT in a Chinese population using a systematic analysis. Methods: In a case study conducted at the First Affiliated Hospital of Xinjiang Medical University between Jan 2019 and Dec 2021, we examined a total of 700 cases of EHT along with 700 corresponding controls. The serum concentrations of various lipid parameters were measured by enzymatic method, while the genotyping of the SNP was performed using the improved multiplex ligation detection reaction (iMLDR) method. The independent risk factors of EHT were identified from multivariable logistic regression analysis. The nomogram prediction model that incorporated the APOA5 genetic variations and clinical variables was constructed. In addition, receiver operating characteristic (ROC) curve and Hosmer-Lemeshow test were conducted to determine the performance of the nomogram model. The optimal threshold was calculated based on Youden index. Results: Our study revealed a higher prevalence of the G allele of the rs662799 variant in individuals diagnosed with EHT compared to the control group. Logistic regression analysis indicated that with the adjustment of other confounders, the observed difference between the two groups remained statistically significant [odds ratio (OR) =1.519; 95% confidence interval (CI): 1.203-1.917; P<0.001]. Based on 8 independent risk factors including APOA5 rs662799 G allele, age, body mass index (BMI), smoking, diabetes, education, low-density lipoprotein cholesterol (LDL-C), and TG, we constructed a novel risk evaluation nomogram of EHT. The area under the ROC curve of the nomogram was 0.722 (95% CI: 0.693-0.752; P<0.001) and 0.747 (95% CI: 0.690-0.804; P<0.001) for the training and validation set, respectively. Furthermore, the Hosmer-Lemeshow test indicated excellent calibration performance, yielding P values of 0.969 for the training set and 0.761 for the validation set. Conclusions: In our study, the rs662799 variant of the APOA5 gene was significantly associated with susceptibility to EHT. A nomogram for the early prediction of EHT in in the Chinese population was successfully constructed and validated. The nomogram can provide a visual assessment of the risk of EHT for clinical consultation.

Association of Polymorphic Variants of TCF7L2 and PPARG Genes with Metabolic Markers in Patients with Early Disorders of Carbohydrate Metabolism.

We performed complex analysis of the association of polymorphic variants rs7903146 of the TCF7L2 gene and rs1801282 of the PPARG gene with metabolic parameters, insulin resistance, and ß-cell function in a group of patients with early signs of carbohydrate metabolism disturbances in a sample of Tyumen citizens. The study group consisted of 64 people (39 women, 25 men) aged 40-70 years. The distribution of frequencies of alleles and genotypes of the polymorphic markers rs7903146 and rs1801282 was analyzed and associations of carriage of major homozygous polymorphisms with various phenotypic traits were identified. Genotyping for polymorphic variants of TCF7L2 and PPARG genes was performed using allele-specific PCR with primers provided by Synthol company. Carriers of homozygotes for allele C of the polymorphic marker rs7903146 significantly differed from other respondents by a higher level of C-peptide, as well as by the presence of associations with waist circumference, elevated level of glycated hemoglobin, and arterial hypertension. Carriers of homozygotes for the allele C of the rs1801282 polymorphism of the PPARG gene differed from the group of carriers of homozygotes for the allele G and the group of heterozygote carriers by higher levels of triglycerides, as well as the presence of associations with waist circumference and the level of glycated hemoglobin.

The relationship between polymorphism of IGF2BP2 gene rs4402960 and risk of pan-cancer: a meta-analysis and a bioinformatics analysis.

OBJECTIVE: To conduct a meta-analysis and a bioinformatics analysis to assess the relationship between IGF2BP2 gene polymorphism and pan-cancer risk. METHODS: PubMed, EMBASE, and Web of Science were conducted to literature searches. The heterogeneity test was used in five genetic models. Odds ratios (OR), 95% confidence intervals (CI), and p-values were used to evaluate the combined effects of various genetic models. Subgroup analysis and Meta-regression analysis were used to analyze the characteristics of heterogeneity. Sensitivity analysis and publication bias were also performed. Transcriptomic information on IGF2BP2 was downloaded and analyzed from the TCGA and GTEx databases. GEPIA (http://gepia.cancer-pku.cn/) was performed to analyze the relationship between IGF2BP2 expression and cancer tissue. RESULTS: This meta-analysis contained 7 case-control studies, with 5,908 cases and 7,890 controls. There were significant differences in the heterozygous genetic model of IGF2BP2 gene rs4402960 polymorphism (OR = 1.080, 95% CI = 1.003-1.163, p = 0.041). In subgroup analysis based on ethnicity, There was a statistical significant association in Chinese (heterozygous: OR = 1.110, 95% CI = 1.010-1.220, p = 0.030). Bioinformatics analysis found that IGF2BP2 was over-expressed in pan-cancer (p < 0.01). In addition, the Kaplan-Meier estimate showed that there is statistical significance of OS between the low and high IGF2BP2 TPM groups in Lung adenocarcinoma (p <0.001). CONCLUSIONS: To sum up, IGF2BP2 gene polymorphism may be related to cancer risk. IGF2BP2 has diagnostic value in the diagnosis and treatment of pan-cancer.

Genetic predisposition to early mycosis fungoides: investigating genetic polymorphisms in tissue-resident memory T-cell genes.

OBJECTIVES: Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma; it arises from tissue-resident memory T-cells (TRM). In the present study, we investigated potential functional genetic variations that may predispose MF development. METHODS: A case-control study was conducted using whole-exome sequencing, with a focus on genes that are essential to TRM function. RESULTS: We included 21 patients and 19 healthy subjects in the study. Single nucleotide polymorphisms in the following genes were significantly more common in patients than in healthy subjects: GZMB, HLA-DRB1, CD103, and NOTCH1. Moreover, the number of patients carrying single nucleotide polymorphisms in LAG3, NR4A2, and CD26L was significantly greater in the patient group than in the control group. CONCLUSIONS: The presence of genetic variations in one or more TRM functional gene may predispose patients to develop MF. Further studies involving a larger patient population and a comparative analysis of protein expression will be necessary to validate these findings.

Rs4862705 in the melatonin receptor 1A gene is associated with renal function decline in type 1 diabetes individuals.

Aim: The pathogenesis of chronic diabetes complications has oxidative stress as one of the major elements, and single-nucleotide polymorphisms (SNPs) in genes belonging to antioxidant pathways modulate susceptibility to these complications. Considering that melatonin is a powerful antioxidant compound, our aim was to explore, in a longitudinal cohort study of type 1 diabetes (T1D) individuals, the association of microvascular complications and SNPs in the gene encoding melatonin receptor 1A (MTNR1A). Methods: Eight SNPs in MTNR1A were genotyped in 489 T1D individuals. Besides cross-sectional analyses of SNPs with each one of the microvascular complications (distal polyneuropathy, cardiovascular autonomic neuropathy, retinopathy, and diabetic kidney disease), a longitudinal analysis evaluated the associations of SNPs with renal function decline in 411 individuals followed up for a median of 8 years. In a subgroup of participants, the association of complications with urinary 6-sulfatoxymelatonin (aMT6s) concentration was investigated. Results: The group of individuals with a renal function decline ≥ 5 mL min-1 1.73 m-2 year-1 presented a higher frequency of the A allele of rs4862705 in comparison with nondecliners, even after adjustment for confounding variables (OR = 1.84, 95% CI = 1.20-2.82; p = 0.0046). No other significant associations were found. Conclusions: This is the first study showing an association between a variant in a gene belonging to the melatonin system and renal function decline in the diabetic setting.

A west African ancestry-associated SNP on 8q24 predicts a positive biopsy in African American men with suspected prostate cancer following PSA screening.

BACKGROUND: African American (AA) men have the highest incidence and mortality rates of prostate cancer (PCa) among all racial groups in the United States. While race is a social construct, for AA men, this overlaps with west African ancestry. Many of the PCa susceptibility variants exhibit distinct allele frequencies and risk estimates across different races and contribute substantially to the large disparities of PCa incidence among races. We previously reported that a single-nucleotide polymorphism (SNP) in 8q24, rs7824364, was strongly associated with west African ancestry and increased risks of PCa in both AA and Puerto Rican men. In this study, we determined whether this SNP can predict biopsy positivity and detection of clinically significant disease (Gleason score [GS] ≥ 7) in a cohort of AA men with suspected PCa. METHODS: SNP rs7824364 was genotyped in 199 AA men with elevated total prostate-specific antigen (PSA) (>2.5 ng/mL) or abnormal digital rectal exam (DRE) and the associations of different genotypes with biopsy positivity and clinically significant disease were analyzed. RESULTS: The variant allele carriers were significantly over-represented in the biopsy-positive group compared to the biopsy-negative group (44% vs. 25.7%, p = 0.011). In the multivariate logistic regression analyses, variant allele carriers were at a more than a twofold increased risk of a positive biopsy (odds ratio [OR] = 2.14, 95% confidence interval [CI] = 1.06-4.32). Moreover, the variant allele was a predictor (OR = 2.26, 95% CI = 1.06-4.84) of a positive biopsy in the subgroup of patients with PSA < 10 ng/mL and normal DRE. The variant allele carriers were also more prevalent in cases with GS ≥ 7 compared to cases with GS < 7 and benign biopsy. CONCLUSIONS: This study demonstrated that the west African ancestry-specific SNP rs7824364 on 8q24 independently predicted a positive prostate biopsy in AA men who were candidates for prostate biopsy subsequent to PCa screening.

The pleiotropic approach to coronavirus disease-19 pathogenesis: The impact of liver diseases associated host genetic variants.

Coronavirus disease-2019 (COVID-19) is a novel multisystemic viral disease caused pandemic. The disease impact involves liver and associated systems. Undoubtedly, host genetic background influences the predisposition and prediction of infection. Variants among human populations might increase susceptibility or protect against severe outcomes. In this manner, rs738409 variant of patatin-like phospholipase domain-containing protein 3 gene appears to be protective in some populations in spite of its aggravating effect on non-alcoholic fatty liver diseases (NAFLDs) and steatohepatitis. DRB1*15:01 allele of human leukocyte antigen is associated with protective effect in European and Japanese populations. DRB1*03:01 contrarily increases the susceptibility of severe COVID-19 infection in European populations. rs1260326 in glucokinase regulatory protein gene, rs112875651 in tribbles homolog 1 gene, rs429358 in apolipoprotein 1, and rs58542926 in transmembrane 6 superfamily 2 alleles are found related with NAFLD and obesity; thus, hypercoagulability and severe COVID-19 outcomes. In chronic or acute liver diseases, comorbid syndromes are the key factors to explain increased severity. There might not be a direct association between the variant and severe COVID-19 infection. As it is concluded, there are genes and variants known and unknown yet to be studied to reveal the association with disease severity.

Diagnosis and treatment of venous thromboembolism during pregnancy relate to genetic polymorphism.

OBJECTIVES: Previous research had shown that age, a positive family history, comorbidities, major surgical operations, gestation, and use of several medications could increase the incidence of venous thromboembolism (VTE). With the development of medical and clinical individualized treatment, many people exposed to above risk factors did not develop VTE, suggested that genetic factors are also involved in the development of VTE. In this review, we aim to summarize VTE diagnosis and treatment in pregnancy women related to gene polymorphism. METHODS: A comprehensive electronic search using PubMed, MEDLINE, EMBASE and Web of Science was conducted to find relevant journal articles with key search terms including: "pregnancy OR pregnant," "venous thromboembolism OR VTE," "deep vein thrombosis OR DVT," "pulmonary embolism OR PE," and "genetic OR gene." Prominent publications from establishment of database till present were analysed to achieve a deeper understanding of VTE during pregnancy relate to genetic polymorphism, and the information was then collated to form this review. RESULTS: The literature review revealed that inherited thrombophilia significantly associated with the development of VTE, especially the factor V Leiden (FVL) and prothrombin gene mutation (PGM). Furthermore, the role of methylenetetrahydrofolate reductase (MTHFR) gene mutation in the development of pregnancy-related VTE remains controversial, further study is required. In the present study, Marburg I polymorphism (G511 E), c.1538 G>A and c.1601 G>A in Factor V (FV), JAK2V617 F mutation were reported as an independent risk factor for VTE, there is no sufficient evidence to confirm the gene mutation is related to VTE during pregnancy, these factors appearing as another promising potential diagnostic marker of VTE during pregnancy. Besides, the dosages of heparin in the treatment of VTE during pregnancy need be adjusted according to gene polymorphism of these population, particularly FVL or PGM carriers, and this area is not studied deeply, it is worth further study. CONCLUSION: Inherited thrombophilia significantly associated with the development of VTE, especially the FVL and PGM, however the relation between MTHFR gene mutation and pregnancy-related VTE remains controversial, further study is needed. In addition, the dosages of heparin in the treatment of VTE during pregnancy suggested to adjusted based on gene polymorphism in FVL and PGM, and establish better prediction models is a direction of future research.

Structural Impact Assessment of Cytochrome P450 2A13 Polymorphisms Using Molecular Dynamics Simulations.

One of the members of CYP, a monooxygenase, CYP2A13 is involved in the metabolism of nicotine, coumarin, and tobacco-specific nitrosamine. Genetic polymorphisms have been identified in CYP2A13, with reported loss or reduction in enzymatic activity in CYP2A13 allelic variants. This study aimed to unravel the mechanism underlying the diminished enzymatic activity of CYP2A13 variants by investigating their three-dimensional structures through molecular dynamics (MD) simulations. For each variant, MD simulations of 1000 ns were performed, and the obtained results were compared with those of the wild type. The findings indicated alterations in the interaction with heme in CYP2A13.4, .6, .8, and .9. In the case of CYP2A13.5, observable effects on the helix structure related to the interaction with the redox partner were identified. These conformational changes were sufficient to cause a decrease in enzyme activity in the variants. Our findings provide valuable insights into the molecular mechanisms associated with the diminished activity in the CYP2A13 polymorphisms.

Shared and distinct genetics of pure type 1 diabetes and type 1 diabetes with celiac disease, homology in their auto-antigens and immune dysregulation states: a study from North India.

AIM: This study was undertaken to explicate the shared and distinctive genetic susceptibility and immune dysfunction in patients with T1D alone and T1D with CD (T1D + CD). METHODS: A total of 100 T1D, 50 T1D + CD and 150 healthy controls were recruited. HLA-DRB1/DQB1 alleles were determined by PCR-sequence-specific primer method, SNP genotyping for CTLA-4 and PTPN22 was done by simple probe-based SNP-array and genotyping for INS-23 Hph1 A/T was done by RFLP. Autoantibodies and cytokine estimation was done by ELISA. Immune-regulation was analysed by flow-cytometry. Clustering of autoantigen epitopes was done by epitope cluster analytical tool. RESULTS: Both T1D alone and T1D + CD had a shared association of DRB1*03:01, DRB1*04, DRB3*01:07/15 and DQB1*02. DRB3*01:07/15 confers the highest risk for T1D with relative risk of 11.32 (5.74-22.31). Non-HLA gene polymorphisms PTPN22 and INS could discriminate between T1D and T1D + CD. T1D + CD have significantly higher titers of autoantibodies, expression of costimulatory molecules on CD4 and CD8 cells, and cytokine IL-17A and TGF-ß1 levels compared to T1D patients. Epitopes from immunodominant regions of autoantigens of T1D and CD clustered together with 40% homology. CONCLUSION: Same HLA genes provide susceptibility for both T1D and CD. Non-HLA genes CTLA4, PTPN22 and INS provide further susceptibility while different polymorphisms in PTPN22 and INS can discriminate between T1D and T1D + CD. Epitope homology between autoantigens of two diseases further encourages the two diseases to occur together. The T1D + CD being more common in females along with co-existence of thyroid autoimmunity, and have more immune dysregulated state than T1D alone.