AC Genotype Research Articles

Interleukin-10-592 polymorphism: impact on relapse and survival after allogeneic hematopoietic stem cell transplantation in children with hematological malignancies

PurposeInterleukin-10 (IL-10) potentially can promote the development of alloimmunity. The aim of this study was to investigate if the IL-10-592 CC genotype in the donor reduces the risk of relapse after hematopoietic stem cell transplantation (HSCT) and if that has an impact on event-free survival (EFS) and overall survival (OS).MethodsA cohort of 211 children with acute lymphoblastic leukemia (n = 99), acute myeloid leukemia (n = 69), myelodysplastic syndrome (n = 31) or chronic myeloid leukemia (n = 12) who underwent hematopoietic stem cell transplantation (HSCT) in a single center and their respective donors were genotyped of IL-10 gene for rs1800872 using TaqMan real-time polymerase chain reaction.ResultsThe IL-10-592 CC genotype was detected in 107 of the 211 donors (50.7%) and in 106 of the 211 patients (50.2%). Genotype AC was found in 95 donors (45.0%) and in 90 patients (42.7%). Nine donors (4.3%) and 15 patients (7.1%) were homozygous for AA. Ultimately, we observed a significantly reduced incidence of relapse rate (RR) in patients who were transplanted from a donor with the IL-10-592 CC genotype (19% versus 43% (AC) versus 49% (AA); P = 0.0007). In addition, a significant increase of EFS (P = 0.004) and OS (P = 0.006) was detected if the IL-10-592 CC genotype is present in the donor. The occurrence of the IL-10-592 CC genotype, in either donors or recipients, had no significant impact on acute and chronic graft-versus-host disease. In addition, the IL-10-592 genotype of the recipients was not relevant for the RR (P = 0.47434), the EFS (P = 0.840), and the OS (P = 0.535).ConclusionThe IL-10-592 CC genotype in the donor was associated with a significant decrease of RR which led to a significant increase of EFS and OS after HSCT. This is the first study to describe an association of the IL-10 gene polymorphism with RR, EFS, and OS after HSCT. Selecting a donor with the IL-10-592 CC genotype could be a useful therapeutic strategy for improving the outcome after allogeneic HSCT.

C677T and A1298C MTHFR gene polymorphisms and response to fluoropyrimidine-based chemotherapy in Mestizo patients with metastatic colorectal cancer.

To assess the association between C677T and A1298C methylenetetrahydrofolate reductase (MTHFR) single-nucleotide polymorphisms (SNPs) and response to first-line fluoropyrimidine-based chemotherapy for metastatic colorectal adenocarcinoma. A total of 68 patients were prospectively followed up in San Juan de Dios Hospital (San José, Costa Rica) from January 2019 to November 2020. Patients received first-line therapy with capecitabine or 5-fluorouracil in combination with oxaliplatin or irinotecan. Germline and somatic DNA was extracted from blood samples and paraffin-embedded tissue, respectively. Overall response rate (partial response + complete response) was assessed according to RECIST 1.1 criteria. Cox regression models were performed to identify the effect of MTHFR C677T and A1298C SNPs on progression-free survival (PFS) and overall survival (OS) (NCT registration number: 03852290). Patients harboring one or both T alleles of the MTHFR C677T SNP had better overall response than homozygous wild-type individuals [odds ratio (OR): 3.21; 95% confidence interval (CI), 1.05-9.81; P = 0.03]. No association was found between the MTHFR A1298C genotypes and overall response (OR: 0.75; 95% CI, 0.26-2.20; P = 0.60). Patients with the MTHFR 677 TT and CT genotypes had longer PFS than CC individuals (hazard ratio: 0.53; 95% CI, 0.28-0.98; P = 0.045), even after adjustment for confounders (hazard ratio: 0.50; 95% CI, 0.25-0.98; P = 0.04). We found no association between the MTHFR A1298C SNP and PFS (hazard ratio: 1.35; 95% CI, 0.72-2.55; P = 0.34). None of the SNPs was associated with OS. Patients carrying at least one mutant allele of the MTHFR C677T SNP had a better overall response and longer PFS than wild-type homozygous patients.

Assessment of rs4588 Allele Impact on 25-OH-D Concentration in Blood of Caucasian Adults

ObjectivesAn important point of contention is whether genetic variation has meaningful impact on vitamin D adequacy on top of known modulators like season, fat mass, skin pigmentation and geographic latitude. Answers could come from information generated by numerous published studies. As a first step towards integration of these often diverse data, the impact of the commonly measured single nucleotide variant rs4588 of the GC gene on 25-hydroxy vitamin D (25OHD) concentration in blood of healthy Caucasian adults was assessed with a systematic review and metaanalysis of published findings. MethodsSelection criteria for inclusion of studies in the analyses were Caucasian healthy adults and listing of average 25OHD concentration in plasma or serum by rs4588 or the tightly linked rs2282679 genotypes. Percent differences between genotypes were extracted from included publications. A random-effects model of metaanalysis was performed using STAT 16. ResultsOf the studies meeting inclusion criteria, published between 2005 and 2019, 35 reported genotype-specific 25OHD concentrations in a total of 59,939 Caucasian adults. The weighted averages were 25.3, 23.2 and 20.4 ng/ml for the GC rs4588 CC, AC and AA genotypes. Relative differences are more informative than absolute concentrations since they are much less affected by calibration discrepancies. The CA carriers had 6.8% lower concentrations than CC carriers and AA carriers 15% lower concentrations when using averages weighted by cohort size. Eight of the included studies with a total number of 15,329 individuals reported standard deviations for the genotype-specific 25OHD concentrations and only these were included for the metaanalysis. The average effect size was –0.44 (95% CI; –0.89, 0.01) for carriers of a single rs4588 A allele, and –0.59 (95% CI; –0.94, –0.23) for carriers of two AA alleles. Heterogeneity was high and statistically significant. ConclusionsThe combined data indicate that 25OHD concentrations differ by GC rs4588 genotype in healthy adults with predominantly Caucasian ancestry with an additive effect of about 9% per allele. The much lower than average 25OHD concentrations in the about 8% GC rs4588 AA genotype carriers should draw attention to this commonly ignored group when it comes to health risks related to vitamin D deficiency. Funding SourcesUNC Nutrition Research Institute internal support

The Influence of rs1859168 Polymorphism on Serum Expression of HOTTIP and Its Target miR-615-3p in Egyptian Patients with Breast Cancer.

Background: Polymorphisms of long noncoding RNAs are lately documented as hazardous factors for the development of numerous tumors. Furthermore, the evaluation of noncoding RNAs has emerged as a novel detector of breast cancer patients. We aimed to genotype the HOXA transcript at the distal tip (HOTTIP) rs1859168 and assess its relationship with the levels of the serum HOTTIP and its target miR-615-3p in patients with breast cancer (BC). Methods: One hundred and fifty-one patients with BC, 139 patients with fibroadenoma (FA), and 143 healthy participants were incorporated into the current study. The genotyping of rs1859168 and the measurements of the HOTTIP and miR-615-3p levels were assessed using quantitative real-time PCR. Results: We revealed a significant association between each of the CC genotypes, C allele, dominant and recessive models, and the increased risk of BC (p = 0.013, p < 0.001, p < 0.001, and p < 0.001, respectively) relative to the healthy controls. Similarly, the CC genotype, C allele, and recessive model were observed to be related to the increased incidence of BC with respect to FA (p < 0.001 for all). A significant upregulation of HOTTIP and a marked decrease of miR-615-3p were verified in patients with BC compared to each of the healthy individuals, patients with FA, and the non-BC group (healthy subjects + FA) (p < 0.001 for all). A significant negative correlation was demonstrated between the expression of HOTTIP and miR-615-3p in the serum of patients with BC. The HOTTIP expression was upregulated, while that of miR-615-3p was downregulated in patients with BC who carried the CC genotype with respect to those who carried the AA or AC genotypes (p < 0.05 for all). Conclusions: The genetic variants of rs1859168 are linked to an increased susceptibility to BC. Moreover, HOTTIP and miR-615-3p may be used as novel indicators and targets for the treatment of patients with BC.

BRCA2 3'-UTR Polymorphism rs15869 Alters Susceptibility to Papillary Thyroid Carcinoma via Binding hsa-mir-1178-3p.

ObjectiveTo investigate the associations of polymorphisms in the following DNA double-strand break repair (DSBR) genes with papillary thyroid carcinoma (PTC) risk (including RAD51 rs11852786, RAD51B rs963917, BRCA1 rs12516 and rs8176318, BRCA2 rs15869, XRCC4 rs2035990 and XRCC5 rs2440).Materials and MethodsA matched case–control study was implemented to examine associations between PTC risk and the above polymorphisms. Subsequently, we evaluated the effects of the potential PTC susceptibility-related variant rs15869 on BRCA2 mRNA secondary structure and BRCA2 expression through bioinformatics analysis and experiment validation. Additionally, luciferase assay was used to identify whether rs15869 polymorphism can substantially affect the binding of hsa-miR-1178-3p to BRCA2 mRNA. Finally, Pearson correlation analysis was performed to determine the correlation between the expression of hsa-miR-1178-3p and BRCA2 mRNA and protein in thyroid tissues harboring rs15869 different genotypes.ResultsBRCA2 rs15869 CC genotype was associated with a higher risk of PTC than its AA genotype. Subsequently, stratified analyses came to the same conclusion in the female or age<50 population. Furthermore, we confirmed that the A-to-C substitution of rs15869 changed BRCA2 mRNA secondary structure and contributed to a decreased BRCA2 expression. Mechanistically, a significantly decreased luciferase activity verified a greater binding between hsa-miR-1178-3p and rs15869 C allele, but not the A allele, which was evidenced by the significant negative correlation between hsa-miR-1178-3p with BRCA2 mRNA and protein levels in thyroid tissues with AC and CC genotype but not AA genotype at rs15869.ConclusionBRCA2 rs15869 is characterized as a potential biomarker associated with PTC risk, highlighting the contribution of the hsa-miR-1178-3p via functional exploration.

Correlation between an intronic SNP genotype and ARL15 level in rheumatoid arthritis

ADP ribosylation factor like protein 15 (ARL15) was identified as a novel susceptibility gene for rheumatoid arthritis (RA) based on a genomewide association study in a north Indian cohort. Mechanism of its action and functional relevance in RA biology remain largely unknown. In this study, we aimed to establish (i) ARL15 protein level in sera samples of RA patients; and (ii) its correlation, if any, with the RA associated ARL15 intronic single-nucleotide polymorphism (SNP) rs255758 (A>C). DNA, RNA and sera were isolated from blood samples of 117 RA patients and 25 age-matched healthy controls recruited at All India Institute of Medical Sciences, New Delhi with institutional ethical committee clearance. SNP rs255758 (A>C) was genotyped by Sanger sequencing; ARL15 RNA and protein levels were estimated by quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA), respectively; and genotype-phenotype correlation established using Mann-Whitney nonparametric test. Very low level of ARL15 expression in human blood was confirmed at both RNA and protein levels. Genotype-wise distribution showed increased levels (P = 0.05) of ARL15 protein in RA patients with the homozygous variant (CC) as compared to AA + AC genotypes of rs255758. This first-ever correlation between higher ARL15 protein levels and the intronic susceptibility genotype (CC; rs255758) in RA patients may be of diagnostic and therapeutic relevance encouraging additional investigations.

PENGARUH PERLAKUAN SUHU DAN BEBERAPA GENOTIPE TERHADAP VIABILITAS DAN VIGOR BENIH KUBIS BUNGA (BRASSICA OLERACEA VAR. BOTRYTIS L.) PADA DATARAN RENDAH

The aim of this study was to obtain the best temperature on several genotypes so as to increase the best viability and vigour of cauliflower seeds in the lowlands. The research was conducted at the Laboratory Agronomy, OPT and Soil Biotechnology Faculty of Agriculture, Singaperbangsa Karawang University. The research method used was an experimental method with a two-factor completely randomized design (CRD). The first factor is temperature which consists of room temperature without air conditioning (P0), air-conditioned room temperature (P1) and refrigerator temperature (P2). The second factor is genotypes consisting of Viola (B1), Tegar 45 (B2), Snow Waltz (B3), Jayanti (B4), Giga (B5), Snow White (B6), Diamond (B7), Orient (B8). , Roo So 45 (B9), Forum (B10), Bima (B11), F1 Hybrid (B12) and Arjuna (B13). Each treatment was repeated 2 times so that 78 experiments were obtained and 2 times planting (before and after storage). The results of the pre-storage experiment showed that there was no interaction between temperature treatment and several genotypes, but in the post-storage experiment, there were an interaction with the parameters of germination, concurrency of growth, vigor index and maximum growth potential, while for parameters of moisture content, normal germinated dry weight and length of sprouts. indicates there is no interaction. The best treatment was room temperature without AC genotype Roo So 45 (P0B9).&#x0D; &#x0D; Keywords: Cabbage flower, genotype, temperature, , viability, vigour.

Association of Myopia and Genetic Variants of TGFB2-AS1 and TGFBR1 in the TGF-β Signaling Pathway: A Longitudinal Study in Chinese School-Aged Children.

BackgroundMyopia is a complex multifactorial condition which involves several overlapping signaling pathways mediated by distinct genes. This prospective cohort study evaluated the associations of two genetic variants in the TGF-β signaling pathway with the onset and progression of myopia and ocular biometric parameters in Chinese school-aged children.MethodsA total of 556 second grade children were examined and followed up for 3.5 years. Non-cycloplegic refraction and ocular biometric parameters were measured annually. Multivariate regression analysis was used to assess the effect of the TGFBR1 rs10760673 and TGFB2-AS1 rs7550232 variants on the occurrence and progression of myopia. A 10,000 permutations test was used to correct for multiple testing. Functional annotation of single nucleotide polymorphisms (SNPs) was performed using RegulomeDB, HaploReg, and rVarBase.ResultsA total of 448 children were included in the analysis. After adjustments for gender, age, near work time and outdoor time with 10,000 permutations, the results indicated that the C allele and the AC or CC genotypes of rs7550232 adjacent to TGFB2-AS1 were associated with a significantly increased risk of the onset of myopia in two genetic models (additive: P’ = 0.022; dominant: P’ = 0.025). Additionally, the A allele and the AA or AG genotypes of rs10760673 of TGFBR1 were associated with a significant myopic shift (additive: P’ = 0.008; dominant: P’ = 0.028; recessive: P’ = 0.027). Furthermore, rs10760673 was associated with an increase in axial length (AL) (P’ = 0.013, β = 0.03) and a change in the ratio of AL to the corneal radius of curvature (AL/CRC) (P’ = 0.031, β = 0.003). Analysis using RegulomeDB, HaploReg, and rVarBase indicated that rs7550232 is likely to affect transcription factor binding, any motif, DNase footprint, and DNase peak.ConclusionThe present study indicated that rs10760673 and rs7550232 may represent susceptibility loci for the progression and onset of myopia, respectively, in school-aged children. Associations of the variants of the TGFBR1 and TGFB2-AS1 genes with myopia may be mediated by the TGF-β signaling pathway; this hypothesis requires validation in functional studies. This trial was registered as ChiCTR1900020584 at www.Chictr.org.cn.

The role of galectin-3 and its genetic variants in tumor risk and survival of patients with surgically resected early-stage non-small cell lung cancer.

Background The aim of this study was to investigate the possible relationship between galectin-3 gene variants, serum level, gene expression level, and the risks and survivals of resectable non-small cell lung cancer patients. Methods The rs4644 and rs4652 variants of galectin-3 were genotyped by TaqMan single nucleotide polymorphism assay using genomic deoxyribonucleic acid isolated from the peripheral blood of 65 (54 males, 11 females; mean age: 60.1±11.9 years; range, 34 to 83 years) with Stage IA-IIIA non-small cell lung cancer who underwent primary surgical treatment and 95 healthy individuals (48 males, 47 females; mean age: 53.9±13.5 years; range, 32 to 87 years) between March 2017 and September 2018. Circulating galectin-3 levels in serum samples of the patient and control groups were assessed by enzyme-linked immunosorbent assay. Messenger ribonucleic acid expression of galectin-3 in tumor and surrounding tissues of the patient group was examined by real-time quantitative polymerase chain reaction. Both predictive and prognostic significance of the results were analyzed. Results The presence of angiolymphatic invasion was significant in the patients with rs4652 AA genotype (p=0.04). Serum galectin-3 levels were significantly higher in the patients than the controls (p<0.0001). The patients with rs4644 CA/CC (p<0.0001 and p<0.0001) and rs4652 AA/AC (p=0.001 and p<0.0001) genotypes had higher serum galectin-3 levels than their corresponding controls. Serum galectin-3 levels increased in the presence of vascular invasion in patients with both rs4644 AC (p=0.03) and rs4652 AC (p=0.019) genotypes. The receiver operating characteristic curve suggested serum galectin-3 level as a strong predictive marker for the patient group with a cut-off value of 17.089 ng/mL (area under the curve: 0.910±0.04; 95% confidence interval: 0.832-0.988; p<0.001). Univariate analysis revealed the association of lower serum galectin-3 levels with better survival (p=0.048). Multivariate survival analysis showed that only high serum galectin-3 levels tended to be related to survival of the patients (hazard ratio: 5.106; 95% confidence interval: 0.956-27.267; p=0.056). Conclusion The presence of galectin-3 gene variants may lead to histopathological differences among patients with non-small cell lung cancer. Serum galectin-3 level may be a valuable diagnostic biomarker and be associated with survival of these patients.

Roles of endothelial lipase gene related single nucleotide polymorphisms in patients with coronary artery disease

The current work focused on evaluating the roles of endothelial lipase gene (LIPG) related single nucleotide polymorphisms (SNPs) in patients with coronary artery disease (CAD). This study involved 1,883 subjects with 959 CAD patients and 924 healthy controls. Data were harvested to assess the association of LIPG related SNPs including rs3744841, rs3744843, rs3813082 and rs2000813 with the risk of CAD. The CC+AC genotype in rs3813082 played a protective role for CAD [odds ratio (OR)=0.709, P=0.039]. Differences existed in apolipoprotein-A1 (Apo-A1) and high-density lipoprotein-cholesterol (HDL-C) levels in rs3744843 variant between control and CAD groups. The rs3744841 variant increased the levels of total cholesterol (TC), HDL-C, low-density lipoprotein cholesterol (LDL-C), Apo-A1 and Lipoprotein a (LPa) in the CAD group and TC, LDL-C, HDL-C, Apo-B, Apo-A1 in the control group. The triglyceride (TG) level was lower in rs2000813 variant in the CAD group and elevated in the control group. The rs2000813 variant decreased the number of vascular stenosis while rs3744843 and rs3744841 variants increased the number of vascular stenosis in CAD patients. This study explored the roles of LIPG related SNPs in CAD, showing that CC+AC genotype in rs3813082 was a protective factor for CAD. The rs3744843, rs3744841 and rs2000813 variants were associated with the levels of lipid parameters in CAD patients. The rs3744843, rs3744841 and rs2000813 variants influenced the number of vascular stenosis in CAD patients. The results of our study might be a promising reference for preventing CAD.

Polymorphisms in the stearoyl-CoA desaturase gene modify blood glucose response to dietary oils varying in MUFA content in adults with obesity.

Diets varying in SFA and MUFA content can impact glycaemic control; however, whether underlying differences in genetic make-up can influence blood glucose responses to these dietary fatty acids is unknown. We examined the impact of dietary oils varying in SFA/MUFA content on changes in blood glucose levels (primary outcome) and whether these changes were modified by variants in the stearoyl-CoA desaturase (SCD) gene (secondary outcome). Obese men and women participating in the randomised, crossover, isoenergetic, controlled-feeding Canola Oil Multicenter Intervention Trial II consumed three dietary oils for 6 weeks, with washout periods of ˜6 weeks between each treatment. Diets studied included a high SFA/low MUFA Control oil (36·6 % SFA/28·2 % MUFA), a conventional canola oil (6·2 % SFA/63·1 % MUFA) and a high-oleic acid canola oil (5·8 % SFA/74·7 % MUFA). No differences in fasting blood glucose were observed following the consumption of the dietary oils. However, when stratified by SCD genotypes, significant SNP-by-treatment interactions on blood glucose response were found with additive models for rs1502593 (P = 0·01), rs3071 (P = 0·02) and rs522951 (P = 0·03). The interaction for rs3071 remained significant (P = 0·005) when analysed with a recessive model, where individuals carrying the CC genotype showed an increase (0·14 (sem 0·09) mmol/l) in blood glucose levels with the Control oil diet, but reductions in blood glucose with both MUFA oil diets. Individuals carrying the AA and AC genotypes experienced reductions in blood glucose in response to all three oils. These findings identify a potential new target for personalised nutrition approaches aimed at improving glycaemic control.

Genetic association between interleukin-10 gene rs1518111 and rs3021094 polymorphisms and risk of type 1 diabetes and diabetic nephropathy in Egyptian children and adolescents.

Genetic and environmental factors have been implicated in etiopathogenesis and progression of type 1 diabetes mellitus (T1DM) and diabetic nephropathy (DN). Genetic association between interleukin-10 (IL-10) single nucleotide polymorphisms (SNPs) with T2DM and DN was recently established. We aimed to explore the potential genetic risk of IL-10 gene rs1518111 and rs3021094 SNPs in susceptibility to T1DM and DN. Cross-sectional study included 140 T1DM children, of whom 74 had DN and 90 controls. IL-10 gene rs1518111 and rs3021094 SNP were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique of the extracted genomic DNA from participants. Odds ratios (ORs) and 95% confidence intervals (CIs) were applied to explore the association between IL-10 gene polymorphisms and the risk of T1DM and DN. For rs1518111 SNP, AA genotype was associated with high risk of T1DM (OR = 4.53; CI = 2.11-9.74; p < 0.001), while A allele was associated with high risk of both T1DM (OR = 3.35; CI = 2.20-5.09; p < 0.001) and DN (OR = 2.36; CI = 1.27-4.38; p = 0.006). For rs3021094 SNP, AC genotype displayed lower risk to develop T1DM (OR = 0.35; CI = 0.13-0.94; p = 0.037), while A allele displayed higher risk to develop T1DM (OR = 1.69; CI = 1.11-2.56; p = 0.013). GA and AC haplotypes of rs1518111 and rs3021094 had lower ORs for having T1DM and DN, while GC had lower OR for having T1DM. AA genotype and A allele of IL-10 rs1518111 SNP could be linked to increased risk for T1DM and DN among Egyptian children. None of rs3021094 genotypes or alleles displayed significant association with DN. GA and AC haplotypes could be protective against T1DM and DN susceptibility.

Association between Single Nucleotide Polymorphism rs9891119 of STAT3 Gene and the Genetic Susceptibility to Type 2 Diabetes in Chinese Han Population from Guangdong.

Background The aim of this study was to investigate the association between single nucleotide polymorphism (SNP) rs9891119 of the signal transducer and activator of the transcription 3 (STAT3) gene and genetic susceptibility to type 2 diabetes in Chinese Han population from the Guangdong province. Objective The aim of the present study was to explore the relationship between single nucleotide polymorphism rs9891119 of STAT3 gene and type 2 diabetes mellitus (T2DM), which provides a basis for molecular genetic research on the pathogenesis of T2DM in Chinese Han population. Methods In our case-control study, the SNP rs9891119 was picked out from the STAT3 gene and the SNP genotyping was performed by using the SNPscan™ kit in 1092 patients with type 2 diabetes as cases and 1092 normal persons as controls. The distributions of genotype and allele frequencies in two groups were analyzed by SPSS 20.0 software. Results Our results showed that the alleles of A and C of rs9891119 of the STAT3 gene were 54.3 and 45.7% in patients with type 2 diabetes, while 55.5% and 44.5% in the normal persons, which have no statistical significance (P > 0.05). There were also no significant differences in AA, AC, and CC genotype frequencies between type 2 diabetes patients and normal persons. There were no significant differences in codominant, dominant, recessive, and overdominant genetic models of SNP rs9891119 before and after adjusting the covariant factors (P > 0.05). Conclusions Therefore, genetic susceptibility to type 2 diabetes may be not associated with SNP rs9891119 of the STAT3 gene in Chinese Han population from the Guangdong province.

Impact of MASP2 gene polymorphism and gene-tea drinking interaction on susceptibility to tuberculosis

Mannan-binding lectin-associated serine protease-2 (MASP-2) has been reported to play an important role as a key enzyme in the lectin pathway of the complement system. The objectives of our study were to determine whether the single-nucleotide polymorphism (SNPs) of MASP2 and the gene-tea drinking interaction were associated with the susceptibility to TB. In total, 503 patients and 494 healthy controls were contained. Three SNPs (rs12142107, rs12711521, and rs7548659) were genotyped. The association between the SNPs and susceptibility to TB were investigated by conducting multivariate unconditional logistic regression analysis. The gene-tea drinking interactions were analyzed by the additive model of marginal structural linear odds models. Both genotype AC + AA at rs12711521 of MASP2 genes and genotype GT + GG at rs7548659 of MASP2 genes were more prevalent in the TB patient group than the healthy control group (OR: 1.423 and 1.439, respectively, P < 0.05). In addition, The relative excess risk of interaction (RERI) between tea drinking and rs12142107, rs12711521, and rs7548659 of MASP2 genes was found to suggest negative interactions, which reached − 0.2311 (95% confidence interval (CI): − 0.4736, − 0.0113), − 0.7080 (95% CI − 1.3998, − 0.0163), and − 0.5140 (95% CI − 0.8988, − 0.1291), respectively (P < 0.05). Our finding indicated that the SNPs (rs12711521 and rs7548659) of MASP2 were associated with the susceptibility to TB. Furthermore, there were negative interactions between tea drinking and rs12142107, rs12711521, and rs75548659 of MASP2 gene, respectively. Our research provides a basis for studying the pathogenesis and prevention of tuberculosis.

Association between IL-18 and IL-6 gene polymorphisms and the risk of T1D in Egyptian children.

To test the involvement between IL-18 and IL-6 genetic polymorphisms and susceptibility to Type 1 diabetes (T1D). Single nucleotide polymorphisms (SNPs) at positions -607A/C and - 137G/C in IL-18 promoter region were examined by sequence specific primers-polymerase chain reaction (SSP-PCR) and position -174G/C in promoter region of IL-6 gene which analyzed by Mutagenically Separated PCR (MS-PCR) in 104 T1D participants and 114 controls. IL-18 -137GC and -137CC genotypes and -137C allele were significantly decreased in T1D subjects (P < 0.05), while -137GG genotype was insignificantly increased as compared to controls. A significant decrease was detected in haplotype -137C/-607C frequency in T1D participants compared with controls (OR = 0.04, P < 0.001). There was significant association between IL-18 -607 of (CC, AC and AA genotypes) in age at diagnosis, glycated hemoglobin (HbA1c) and higher body mass index (BMI) (P < 0.05). This study demonstrated that IL-18 gene promoter polymorphisms might be associated with susceptibility to T1D in Egyptian children. Individuals carrying CC genotype at position -137 of IL-18 promoter may be at a low risk of T1D progression. Additionally, the susceptible combination of IL-18 and IL-6 cytokine genes associated with T1D highlight their risk toward the disease. The online version contains supplementary material available at 10.1007/s40200-021-00763-w.

Influence of Methylenetetrahydrofolate Reductase C677T and A1298C Polymorphism on High-Dose Methotrexate-Related Toxicities in Pediatric Non-Hodgkin Lymphoma Patients.

PurposeThis retrospective study aimed to investigate the relationships between the methylenetetrahydrofolate reductase (MTHFR) C677T/A1298C and high-dose methotrexate (HD-MTX)-related toxicities in pediatric non-Hodgkin lymphoma (NHL) patients.Patients and MethodsWe reviewed the medical records of 93 NHL patients aged under 18 years who received HD-MTX therapy at the dose of 5 g/m2 with 24-h infusion at Sun Yat-sen University Cancer Center between 2014 and 2019.ResultsThere were 61 males and 32 females, with a median age of 8.8 years (0.9–15.8 years). The tumor types included lymphoblastic lymphoma (n = 38), Burkitt’s lymphoma (n = 31), anaplastic large cell lymphoma (n = 18), diffuse large B-cell lymphoma (n = 6). Overall, 355 courses of HD-MTX therapy were prescribed. All patients were rescued with calcium folinate 12 h after the end of MTX infusion. We found that plasma MTX levels > 0.2 μmol/L at 48 h post-infusion increased the risk of developing oral mucositis (2.4% VS. 9.5%, P = 0.018). Also, patients carrying the C677T and T677T genotypes had tendencies to be more susceptible to oral mucositis (P = 0.034). Patients harboring mutant 677T allele were more likely to develop leucopenia (38.5 vs. 50.3%, P = 0.025) and thrombocytopenia (22.0 vs. 32.4%, P = 0.028). For polymorphism A1298C, the mutant genotype played a protective role in vomiting (11.1 vs. 4.3%, P = 0.018) but increased the risk of anemia (23.8 vs. 41.7%, P < 0.001) and leucopenia (38.1 vs. 50.3%, P = 0.021).ConclusionChildhood NHL patients harboring C677T genotype were more vulnerable to oral mucositis, leucopenia, and thrombocytopenia, while those with A1298C genotype were at a decreased risk of vomiting and more likely to develop anemia and leucopenia.

Association of Cytochrome P450 2C9*3 and Angiotensin II Receptor 1 (1166A>C) Gene Polymorphisms With the Antihypertensive Effect of Irbesartan.

To analyze whether the cytochrome P450 enzyme 2C9*3 (CYP2C9*3) and angiotensin II receptor 1 (AGTR1) (1166A>C) gene polymorphisms are associated with the risk of essential hypertension (EH) and the antihypertensive effect of irbesartan. A total of 2,057 EH patients and 286 healthy controls were enrolled for genotyping in which 598 EH patients were given irbesartan 150 mg/day for 4 weeks. Blood pressure of all subjects were determined before and at the end of 4-week treatment. There was no significant difference in genotype frequencies of CYP2C9*3 and AGTR1 (1166A>C) between EH and control groups. Subjects with *1*3/*3*3 genotypes of the CYP2C9*3 gene had larger systolic and diastolic blood pressure reductions (34.9 ± 15.5 vs. 29.3 ± 10.2 mm Hg and 22.8 ± 9.0 vs. 19.6 ± 8.5 mm Hg, respectively) compared with the *1*1 genotype. For AGTR1 (1166A>C) polymorphisms, although there was no significant difference among AC, CC, and AA genotypes, male subjects with AC/CC genotypes had larger systolic and diastolic blood pressure reductions (32.3 ± 1.3 vs. 29.3 ± 0.5 mm Hg and 21.6 ± 0.8 vs. 19.4 ± 0.1 mm Hg, respectively, P < 0.05) in response to irbesartan treatment compared with the AA genotype. Polymorphisms of CYP2C9*3 and AGTR1 (1166A>C) are not significantly different between EH and healthy controls. Male subjects with AC and CC genotypes of AGTR1 (1166A>C) show better antihypertensive effect of irbesartan than the AA genotype.

Association of the Fatty Acid Amide Hydrolase C385A Polymorphism With Alcohol Use Severity and Coping Motives in Heavy‐Drinking Youth

Reduced function of fatty acid amide hydrolase, the catabolic enzyme for the endocannabinoid anandamide, can be inherited through a functional genetic polymorphism (FAAH rs324420, C385A, P129T). The minor (A) allele has been associated with reduced FAAH enzyme activity and increased risk for substance use disorders in adults. Whether this inherited difference in endocannabinoid metabolism relates to alcohol use disorder etiology and patterns of alcohol use in youth is unknown. To examine this question, heavy-drinking youth (n=302; mean age=19.74±1.18) were genotyped for FAAH C385A. All subjects completed a comprehensive interview assessing alcohol use patterns including the Timeline Follow-back Method, Alcohol Use Disorders Identification Test (AUDIT), and Drinking Motives Questionnaire. Analyses of Covariance (ANCOVAs) were conducted to assess differences in drinking patterns and drinking motives between genotype groups, and mediation analyses investigated whether drinking motives accounted for indirect associations of genotype with alcohol use severity. Youth with the FAAH minor allele (AC or AA genotype) reported significantly more drinking days (p=0.045), significantly more frequent heavy episodic drinking (p=0.003), and significantly higher alcohol-related problems and consumption patterns (AUDIT score p=0.045, AUDIT-C score p=0.02). Mediation analyses showed that the association of FAAH C385A with drinking outcomes was mediated by coping motives. These findings extend previous studies by suggesting that reduced endocannabinoid metabolism may be related to heavier use of alcohol in youth, prior to the onset of chronic drinking problems. Furthermore, differences in negative reinforcement-related drinking could account in part for this association.

Association study of interleukin-1 receptor associated kinase 1 rs3027898 A/C gene polymorphism and preeclampsia in Pakistani population.

To find the association between interleukin-1 receptor-associated kinase 1 rs3027898 gene polymorphism and preeclampsia. The case-control study was conducted from October, 2018 to September, 2019 at the Railway General Hospital and the Department of Biochemistry, Islamic International Medical College, Rawalpindi, Pakistan, and comprised patients diagnosed with preeclampsia and healthy controls. The interleukin receptor-associated kinase-1 polymorphism was determined using multiplex tetra primer amplification refractory mutation system polymerase chain reaction. Outcomes were determined in terms of association of interleukin receptor-associated kinase-1 with preeclampsia. Data was analysed using SPSS 22. Of the 160 subjects, 80(50% were cases with a mean age of 30±5.3 years and 80(50%) were controls with a mean age of 27±3.7 years. AC genotype was seen in 45(56.25%) cases and 30(37.5%) controls, AA genotype in 25(31.25%) cases and 30(37.5%) controls, while CC genotype was seen in 10(12.5%) cases and 20(25%) controls (p>0.05). There was no significant association of interleukin receptor-associated kinase-1 genotypes with preeclampsia.

Influence of rs6667202 SNP on Interleukin-10 levels in the gingival fluid of patients with periodontitis grade C

Grade C periodontitis in youngers is characterized by a severe form of periodontitis, and IL10 rs6667202 single nucleotide polymorphism (SNP) has been described as an important feature in this disease etiology. Aim: This study aimed to evaluate, in vivo, the functionality of IL10 rs6667202 SNP on IL-10 gingival fluid levels. Methods: Thirty patients with Perio4C were selected, 15 with the IL10 AA genotype (rs6667202) and 15 with AC/CC genotypes. The gingival fluid was collected from two sites with probing depth ≥ 7 mm and bleeding on probing, and two healthy sites. The IL-10 concentration was determined by Luminex/MAGpix platform. Results: In deep pockets, the IL10 AA genotype presented a lower concentration of IL-10 when compared with AC or CC genotypes (p&lt;0.05). In shallow pockets, no difference between groups was seen (p&gt;0.05). Conclusion: IL10 rs6667202 SNP decreases the production of IL-10 in crevicular fluid, potentially affecting this disease progression.