Meta Gene最新文献

The glutathione S-transferases superfamily (GSTs) act on the detoxification process of xenobiotics and oxidative stress products. The relevance of gene-environment interactions in the development of Amyotrophic lateral sclerosis (ALS) encourages further investigation into the role of genetic factors, such as GSTM1 and GSTT1 deletion polymorphisms. This case-control study evaluated the association of GSTM1 and GSTT1 deletion polymorphism and ALS susceptibility. We genotyped 101 case-patients and 119 controls with multiplex real-time PCR (qPCR) and collected clinical and demographic data from medical records and questionnaires. Our findings demonstrated that alcohol intake was predominant in ALS patients and was significantly associated with the development of the disease (p = 0.01). However, we found no association between ALS risk and GSTM1 (p = 0.85) and GSTT1 (p = 0.90) polymorphisms, even when we combined both genotypes. We analyzed a sample of Brazilian patients, a population within which few studies exist about this rare disease. Thus, new insights seeking the relationship between ALS and mutations, polymorphisms, or the expression of other cell detoxification pathway genes should be encouraged and will provide additional information on the role of antioxidant mechanisms and oxidative stress in the pathogenesis of the disease.

The present meta-analysis was planned to summarize the frequency and effects of A and B alleles of kappa casein gene on milk yield and composition traits by using information of 5715 genotyped cows from 42 published studies (2000 to 2020). The common effect sizes for gene frequency and association were considered as proportion and standardized mean differences (SMDs). Four genetic models viz., additive (AA vs. BB), dominant (AA+ AB vs. BB), completely over dominant (AA+BB vs. AB) and recessive (AA vs. AB+ BB) were used to compare the potential of genotypes in terms of SMDs along with 95% confidence interval (CI) for lactation milk yield and composition traits (fat yield, fat percentage, protein yield and protein percentage). The inconsistency between studies was estimated by heterogeneity statistic (I²). Meta-analysis of allelic frequency under random effects model showed that allele A was predominant as 0.71 (95% CI: 0.65, 0.76) in all genotyped cows. It was significantly higher gene frequency in 1834 Bos indicus cows (0.82, 95% CI: 0.77, 0.88) as compared to 3881 Bos taurus/cross cows (0.67, 95% CI: 0.61, 0.73), with substantial level of heterogeneity (92.73% to 97.68%). The results of association analysis showed that SMDs under all genetic models had significance (P < 0.05) with fat percentage only, with non-significant of heterogeneity (P > 0.05) between studies. For other composition traits and lactation milk yield, non-significant SMDs were observed with low to moderate heterogeneity index. There was not any risk of publication bias as confirmed from Egger's test (P > 0.05). It was concluded that significant molecular marker (allele B) of kappa casein can be used to improve milk fat percentage in dairy cows.

The study of genetic polymorphisms in oncology has acquired great popularity in recent years, mainly as risk factors for the development and progression of different cancers, including those related to the persistence of inflammatory processes. The aim of this work is to realize a systematic review and meta-analysis of selected reports on inflammation-related molecules and their variants and the HNC risk to clarify and to do a more rigorous evaluation of this association. Data extraction, before December 2020, was carried out through the search engines PubMed, Scielo and Sciencedirect from the combination of the following keywords: “gene” “polymorphism” “cytokines” “interleukin” “TNF” “oral cancer” “dysplasia “Head and neck cancer”. A total of 44 and 31 full articles were included in the systematic review and metaanalysis, respectively. For each genotype pooled, the OR observed was IL4VTNR RP1/RP2 0.11 CIs 95% [0.05; 0.24]; IL4 590 CT 0.74 IC95% [0.61; 0.91]; IL6 174 CG (1.65 IC95% [1.16; 2.34], IL6 174 GG 0.57 IC95% [0.41; 0.79], IL8 251 TT 2.40 IC95% [1.39; 4.16], TGFβ 869 CT 2.02 IC95% [1.06; 3.87] reported a significant association between these polymorphisms and HCN risk. The SNPs as IL4VTNR RP2/RP2; IL4 590 CT; IL6 174 GG showed a protective role of mutated variants. To our knowledge, this is the most complete meta-analysis to date of the association between cytokines and other inflammatory molecules and their relationship with the risk of HNC. In conclusion, we can suggest that the presence of mutated variants of IL4, IL6; IL8, and SDF-1 are related to the risk of head and neck cancer. Suggesting that these mutations modify the normal expression of these genes, generating a favorable environment so that, together with environmental factors, cells are led to malignant phenotypes.

Salivary gland tumors are complex neoplastic disorders with unidentified basis. Based on the importance of vitamin D receptor signaling in the pathogenesis of neoplastic conditions, we measured expression of some mRNA coding genes (VDR, CYP24A1 and CYP25B1) and long non-coding RNAs (SNHG16, SNHG6, LINC00346 and LINC00511) from this pathway in 42 paraffin-embedded blocks from 37 patients with different disorders originated from salivary gland. Total RNA was extracted from these samples using commercial kits and expression of mentioned genes was measured in these samples using quantitative real time PCR method. Expression of LINC00511 was lower in tumor samples compared with pleomorphic adenoma (PA) samples (Expression ratio (ER) = 0.08, P value = 0.009). Yet, its expression was higher in PA samples compared with non-cancerous tissues adjacent to carcinoma samples (ER = 21.77, P = 0.009). In addition, its expression was lower in both adenoid cystic carcinoma and mucoepidermoid carcinoma samples compared with PA samples (ER = 0.11, P value = 0.046 and ER = 0.07, P value = 0.017, respectively). Expression of other genes was statistically similar between different lesions. Therefore, LINC00511 might be used as a marker for separation of salivary gland carcinomas from PA samples.

This work was planned to reveal changes in DNA sequence coding for GLUT9 by SLC2A9 gene at exon 8 that may be play a role in gout disease. For this reason 250 male and 150 female patients were involved distributed as follow: patients with gout included 110 male and 15 female, patients with gout and diabetes (T2DM) included 135 male and 90 female, and patients with diabetes and hyperuricemia were 35 male and 15 female and 150 healthy subject served as control. DNA sequence analysis of acquired from each group showed presence of one SNP and DNA deletion in patients with gout disease, five SNPs in patients with gout and T2DM, and one SNP accompanied with rs734553 in patients showing hyperurecemia and T2DM. Translation and alignment of these sequences with control showed significant change in amino acid sequence in all patient groups investigated. DNA polymorphism, codon usage bias, and linkage disequilibrium showed significant association of SNPs detected with gout, and common SNP at position 24,706 of the gene may be with T2DM. This SNP was sent for registration at NCBI under submission ID MW2438870.

This study aims to evaluate the association of Endothelial Nitric Oxide Synthase (eNOS) 4a/b and G1190T polymorphisms with male infertility using a case-control study followed by an in-silico analysis in an Iranian population. This case-control study was conducted on 150 infertile and 155 fertile men as control subjects. The eNOS 4a/b polymorphism was detected using PCR. For G1190T, the PCR fragments were digested with the BanII restriction enzyme. Statistical analysis was done using SPSS Statistics V20. There was a significant difference between infertile and fertile groups in the frequency of the a allele (p = 0.046). In addition, the mentioned allele caused an increase in the risk of idiopathic infertility in the dominant model (p = 0.040). A significant increase occurred in the frequency of the T allele of the G1190T variant in the case group compared to the fertile subjects. In addition, a significant increase occurred in the risk of infertility in the dominant model (p = 0.020). According to bioinformatics analysis results, G1190T substitution altered the splicing pattern of eNOS mRNA as well as the secondary structure of the eNOS protein in some local regions. The present study revealed the significant association of eNOS G1190T and 4a/b gene variants with infertility phenotypes in Iranian men.

Background

Inconclusive findings on the association of polymorphisms in vitamin D receptors (VDR) with the risk of type 1 diabetes mellitus (T1DM) have been obtained in several studies.

Aim

The present meta-analysis was conducted to comprehensively examine the effects of rs7975232, rs1544410, rs2228570, and rs731236 polymorphisms in the VDR gene on the risk of T1DM in the Eastern Mediterranean Region (EMRO) population.

Methods

The PubMed, Scopus, Web of Science, and Google Scholar databases were searched for related literature published up to May 2021. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to measure the strength of the associations. The Newcastle–Ottawa Scale was used to the assessment of the methodological quality of each study. Meta-regression and subgroup analysis were performed to find the potential sources of heterogeneity.

Results

Nine studies consisting of 1618 subjects were included in this study. A protective association for rs1544410 polymorphism under allelic model [OR = 0.597, 95% CI (0.360–0.989), P = 0.045], codominant model [OR = 0.432, 95% CI (0.220–0.851), P = 0.015], and dominant model [OR = 0.460, 95% CI (0.257–0.824), P = 0.009], and a predisposing association under recessive model [OR = 1.607, 95% CI (1.017–2.539), P = 0.042] with T1DM risk was found in selected population. However, no significant associations between rs7975232, rs2228570 and rs731236 and T1DM risk were observed (P > 0.05).

Conclusion

The present meta-analysis suggested that rs1544410 polymorphism might be associated with risk of T1DM in the EMRO population.

Methylmalonic acidemia (MMA) is a rare inborn error of organic acid metabolism presented with wide range of clinical features from mild to severe life-threatening conditions. It is caused mostly due to defective activity of the enzyme methylmalonyl-CoA mutase (MCM), which is encoded by the MUT gene. In this study we analyzed the clinical and biochemical features as well as mutation spectrum in the coding regions (exon 2–13) of the MUT gene and their adjacent intronic consensus splice sites in unrelated MMA patients and healthy individuals. We identified 14 mutations in the MUT gene among which two (c.856G > C and c.1676 + 15C > T) were not reported earlier. Bioinformatics tools were used to explore the molecular consequences of these 14 mutations on MCM activity and correlated these predictions to the phenotypic severities of the patients. Our analysis suggest that a novel mutation c.856G > C (p.E286Q) and a previously reported mutation c.1837C > T (R613C) may have disease causing effect and play important role in methylmalonic acidemia. In addition, we compared the profiles of 79 metabolic features (47 individual metabolite concentrations and 32 ratios) between the MMA patients and healthy controls. Although elevated levels of propionylcarnitine (C3) and ratio of propionylcarnitine (C3) to acetylcarnitine (C2) in blood are considered as the diagnostic features of MMA, this study could clearly distinguish between the MMA patients and the controls based on C3 levels only, but not C3/C2 in a statistically significant manner. In addition to C3, the ratio of argininosuccinic acid (ASA), argininosuccinic acid/arginine (ASA/Arg), and 3-hydroxyisovaleryl−/2-methyl-3-hydroxybutyryl-carnitine/propionylcarnitine (C5OH/C3) were clearly distinguishable between the groups with ≥2 fold changes in concentration.

The balance between maternal immune responses and tolerance is considered as especially critical issue in the dilemma of recurrent pregnancy loss (RPL). Interleukin 6 (IL6) plays a fundamental role in fetal implantation and maintenance of pregnancy. This study aimed to explore the association between IL6–634 G/C gene polymorphisms and their serum levels in females with RPL. An observational case-control study involved 102 controls and 102 cases with RPL. Genotyping of IL6 polymorphism −634 G/C was done with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and their serum levels were measured. There was no statistically significant difference between controls and RPL cases as regard serum IL6 level. The percentage of distribution for allele G was 88.7%, and 78% in controls and cases respectively (p = 0.005). The risk of RPL was decreased by 60% in carriers of allele G (OR = 0.4, 95%CI: 0.2–0.8, p = 0.003). Besides, the homozygote genotype GG (OR = 0.5, 95%CI: 0.28–0.95, p = 0.031), was linked with decreased risk for RPL. The homozygous GG genotype and G allele were associated with decreased risk of RPL in Egyptian females.