G20210A Polymorphism Research Articles

Analysis of FOXE1 rs3758249, IRF6 rs2235375, MTRR A66G in Non-syndromic Cleft Lip and Palate among Indonesian Deutero-Malay Population

Non-syndromic cleft lip and palate (NS-CLP) is one of the most common orofacial malformations, with an incidence of 1 in 700 live births worldwide. This study aimed to determine the risk factor for NS-CLP among the Indonesian Deutero-Malay population by analyzing the FOXE1 rs3758249, IRF6 rs2235375, and MTRR A66G polymorphisms. It is a case-control study, using 50 samples of NS-CLP patients and 50 samples of control (for FOXE1 rs3758249 and MTRR A66G), 30 samples of NS-CLP patients, and 30 samples of control (for IRF6 rs2235375). After DNA was extracted, polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLPs) were performed by using restriction enzymes of Mscl (FOXE1 rs3758249) and Nde1 (MTRR A66G), and sequencing was performed for IRF6 rs2235375. The study was done in the Molecular Genetic Laboratory, Faculty of Dentistry Universitas Padjadjaran Bandung, from September 2023 to January 2024. The chi-square test was used with the exact Fisher's alternatives. The results showed that in FOXE1 3758249, A allele (mutant) was found more in control (OR=0.744, p>0.05), in MTRR A66G, G allele (mutant) was found more in NS-CLP (OR=1.267, p>0.05) meanwhile in IRF6 rs2235375, G allele (mutant) (OR=1.710, p>0.05) was found more in NS-CLP. This study concluded that FOXE1 rs 3758249, IRF6 rs2235375, and MTRR A66G genes were not the risk factor for NS-CLP in the Indonesian Deutero-Malay population.

Significance Of Gene Polymorphisms In Joint Destruction In Reactive Arthritis

in patients with reactive arthritis (ReA), cytokines produced by Th17 cells, one of them IL17, affect cell differentiation, recruitment, activation of immune cells, and release of antimicrobial peptides. Among the cytokines of the IL-17 family, it is IL-17A that is of decisive importance in the induction of pathological bone resorption through direct activation of osteoclast precursors during the formation of the articular syndrome The aim of our work was to study the distribution of allele and genotype frequencies of the polymorphic region G197A (rs2275913) of the IL-17A gene in patients with ReA. As a result of the study, there were no significant differences in the distribution of alleles of the G197A polymorphism of the IL-17A gene in patients with ReA and apparently healthy people. But when comparing genotypic variants, we revealed differences: healthy GG and mutant AA genotypes were more common in patients, while the heterozygous GA genotype was more common in healthy people

Some molecular-genetic determinants of premature aging in women

Background. Accelerated biological aging is associated with age-related diseases and an increased risk of mortality. Genetic predisposition may be an important factor in this process. Aim. To determine the significance of genetic polymorphisms in the VDR and COL1A1 genes in accelerated aging. Materials and methods. The study included 100 women aged 20–35 years, divided into groups with accelerated (Group 1) and normal/slow (Group 2) aging rates. We assessed biological age using V.P. Voytenko's formula. Genetic polymorphisms analyzed were: VDR 283 AG (Bsml), VDR 2 AG (Fokl), COL1A1 1546 GT, COL1A1 -1997 CA. Results. The VDR 283 AG (AA) polymorphism was associated with accelerated aging, occurring more frequently in Group 1 (18% vs 4% in Group 2, p=0.025). The COL1A1 -1997 CA polymorphism was more prevalent in Group 2 (76% vs 56% in Group 1, p=0.035). A multifactorial model identified combinations of polymorphisms that predict accelerated or slow aging with an accuracy of 0.72. Conclusion. Genetic predisposition plays a significant role in accelerated aging. Analysis of VDR and COL1A1 polymorphisms can help identify the risk of premature aging and may serve as a basis for further research and the development of new approaches to prevent age-related diseases.

Methionine Synthase Reductase A66G Variant in Pediatric Acute Lymphoblastic Leukemia Patients.

Methionine synthase reductase, which is encoded by the methionine synthase reductase (MTRR) gene, plays a crucial role in the methylation reactions and the production of DNA and its epigenetic processes. There was a correlation between the MTRR (A66G) polymorphism and the likelihood of developing acute lymphoblastic leukemia (ALL). This study was carried out to investigate the correlation among pediatric ALL cases. Within the participant population of this case-control study, there were 86 individuals who had been diagnosed with ALL, and there were also 150 healthy persons who acted as the control group. To determine the MTRR (A66G) polymorphism, DNA was first extracted and then observed through the use of real-time polymerase chain reaction. The results of the flow cytometry analysis showed that the prevalence of B-cell ALL (B-ALL) was much higher than that of T-cell ALL (T-ALL), which accounted for only 20 cases (23.3%). Upon comparing the hematological parameters of ALL subtypes in patients with T-ALL, it was discovered that there was a statistically significant higher mean total white blood count (P < 0.0005) and mean blast percentage (P = 0.050). Upon examination, it was discovered that both of these figures were much higher than the average. In accordance with the results of the molecular analysis, the occurrence of the MTRR homozygous GG genotype was found to be considerably lower in the patients' group (4.65%) than in the control group (20.67%). However, the MTRR homozygous AA and heterozygous AG were nearly similar in the two groups. The risk of acute lymphoblastic leukemia and MTRR genotypes, on the other hand, exhibited a correlation that was not statistically significant (P = 0.082). The study's findings showed that among pediatric ALL patients, the MTRR A66G polymorphism was not linked to an increased risk of ALL.

Investigating the Matrix of Factor V Leiden (G1691A), Factor II Prothrombin (G2021A), MTHFR C677T and A1298G Polymorphisms in Greek Population: A Preliminary Study.

Thrombophilia, characterized by an increased risk of thrombosis, can result from genetic polymorphisms in clotting factors. This study aims to investigate the prevalence of factor V Leiden (G1691A), factor II prothrombin (G20210A), and MTHFR (C677T and A1298C) polymorphisms in a Greek population, evaluating not only their association with thrombophilia, but also broader health implications. We conducted a cross-sectional study involving one hundred apparently healthy adults from Thessaloniki, Greece. After obtaining informed consent, DNA was isolated and analyzed using real-time PCR to detect the frequencies of the aforementioned polymorphisms. The genetic distribution of the examined polymorphisms aligns closely with that observed in Northern Europe. Factor V Leiden (FVL) and prothrombin G20210A mutations were predominantly wild types, with a small percentage showing heterozygous mutations. The MTHFR C677T and A1298C polymorphisms showed a higher variation in allele frequency. Certain lifestyle factors such as smoking and high body mass index were significantly associated with the occurrence of combined MTHFR genotypes, suggesting an interaction between genetic and environmental risk factors. Family cancer and cardiovascular history was significantly associated with combined FVL and prothrombin G20210A and MTHFR polymorphism heterozygous carriers. Our findings indicate that these genetic polymorphisms are not only pivotal in understanding thrombophilia but also have broader implications for cardiovascular disease and cancer. This study highlights the need for further research into the combined effects of genetic and epigenetic factors on health, which could lead to improved screening and personalized preventive healthcare strategies.

Methionine synthetase A2756G and Cystathionine-β-synthase 844ins68 polymorphisms and coronary artery disease: a meta-analysis

Objective: Methionine synthetase (MS) A2756G and Cystathionine-β-synthase (CBS) 844ins68 gene polymorphisms were indicated to be associated with increased coronary artery disease (CAD) risk. Nevertheless, because the results of each experiment are different, there is no consensus till now. This meta-analysis aimed to clarify the relationship between MS gene A2756G and CBS gene 844ins68 polymorphisms and CAD.Methods: 11,555 participants from 24 individual studies, 2162 participants from 6 individual studies were included in the MS gene A2756G and CBS 844ins68 gene polymorphisms meta-analysis respectively. To determine whether MS gene A2756G or CBS gene 844ins68 polymorphism was associated with CAD risk, a random or fixed-effect genetic model was adopted using pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CIs).Results:MS gene A2756G polymorphism was significantly associated with CAD under recessive (OR: 1.400, 95% CI: 1.119-1.751, P=0.003) and homozygous genetic models (OR: 1.360, 95% CI: 1.084-1.706, P=0.008). In the African subgroup, the association was significant under the allelic, recessive, dominant, heterozygous, homozygous and additive (P<0.05) genetic models. In the Asian subgroup, the association was significant under the allelic, recessive and homozygous genetic models (P<0.05). No significant association was found between CBS 844ins68 gene polymorphism and CAD under all of the genetic models (P>0.05).Conclusions:MS gene A2756G polymorphism was significantly associated with increased CAD risk, especially in the African and Asian population. The G allele carriers of MS gene A2756G polymorphism were more susceptible to be suffered from CAD disease than others.

Interrelationships among MTHFR gene polymorphisms, MTRR gene polymorphisms, and HBV gene BCP 1762/1764 mutations with disease progression in Chronic hepatitis B virus infection patients

Objective Chronic hepatitis B virus (HBV) infection is a major disease that seriously affects the health of patients. In this paper, the relationship among MTHFR gene polymorphism, MTRR gene polymorphism and 1762/1764 mutation in the BCP region of HBV gene with disease progression in chronic HBV patients was studied. Methods A total of 144 chronic HBV infection patients from January 2021 to June 2022 in the Third People’s Hospital of Zigong City, were included as the study subjects. These patients were divided into hepatitis B primary liver cancer patients group (PLC) in 51 cases, Non-primary liver cancer patients group (Non-PLC) in 93 cases, Non-PLC is also divided into chronic hepatitis B virus carriers (CHC) in 49 cases, hepatitis B Live cirrhosis(LC) in 44 cases. MTHFR (C677T), MTRR (A66G) and MTHFR (A1298C) genes polymorphisms were detected by PCR-dissolution curve. The level of HBV-DNA was quantified by real-time PCR, and the 1762/1764 mutation site in the BCP region of the HBV gene were detected by ARMS-PCR. Data were statistically analyzed using the SPSS statistical software. Results The proportion of HBV mutations in BCP region 1762/1764 in PLC group was 82.4%, which was higher than that in LC group (63.6%) and CHC group (51.0%), and the differences were statistically significant (p < 0.05). There were no significant differences in the distribution of MTHFR C677T, MTHFR A1298C and MTRR A66G polymorphisms among CHC, LC and PLC (p > 0.05). The polymorphism distribution of MTHFR C677T, MTRR A66G and MTHFR A1298C genes in patients with chronic hepatitis B virus infection at different stages (CHC, LC and PLC) showed no gender or age differences between and within groups (p > 0.05). Among the patients with MTHFR 677CT + TT, MTRR 66AG + GG and MTHFR 1298AA genotype, the proportion of HBV mutation in BCP region 1762/1764 in PLC group was higher than that in CHC group and LC group, and the differences were statistically significant (p < 0.05). Folate levels in the PLC group were lower than those in the non-PLC group (CHC and LC patients), and the difference was statistically significant compared with the CHC group (p < 0.05). In different MTHFR C677T and MTRR A66G genotypes, the serum GGT activity were statistically significant between mutant PLC and mutant Non-PLC (p < 0.05). Conclusion MTHFR C677T, MTRR A66G and MTHFR A1298C gene polymorphisms distribution have no gender and age differences in chronic hepatitis B virus infection patients. The mutation of HBV gene BCP region 1762/1764 may be associated with the occurrence and development of liver cancer in patients with chronic HBV infection. Single difference of MTHFR C677T, MTHFR A1298C and MTRR A66G gene polymorphisms may have little effect on the disease progression in patients with chronic HBV infection. MTHFR 677CT + TT, MTRR 66AG + GG and MTHFR 1298AA genotype combined with HBV gene BCP region 1762/1764 mutation may be closely related to the occurrence and development of hepatitis B liver cancer.

Association of MTHFR C677T, MTHFRA1298C, and MTRRA66G Gene Polymorphisms with Hyperhomocysteinemia and Its Modulation by the Combined Effect of Vitamin B12 and Folate in Chinese Population with Hypertension

BackgroundIn China, the MTHFR 677T allele, unlike in most Western populations, is a rare genetic variant linked to various disorders. The contributing nutritional and genetic factors to this genetic risk remain unclear. ObjectiveThis study aimed to elucidate the interactions between genetic variations in total homocysteine (tHcy) pathway genes, serum tHcy concentrations, and nutritional factors in a Chinese population with hypertension. MethodsThis study analyzed 1304 Chinese adults with hypertension aged ≥18 y enrolled in the China Precision Nutrition and Health KAP Real World Study (CPNAS). Serum concentrations of vitamin B12 and folate were measured using the magnetic microparticle chemiluminescence method, and tHcy concentrations were measured using Hcy Assay kits. Identification of the MTHFR C677T, MTHFR A1298C, and MTRR A66G polymorphisms was performed via time-of-flight nucleic spectrometry. ResultsOur findings revealed significant sex differences in tHcy concentrations, with males exhibiting higher tHcy concentrations than females (13.95 μmol/L vs. 11.15 μmol/L, P < 0.001). Individuals deficient in both vitamin B12 and folate had an increased risk of hyperhomocysteinemia (H-Hcy) (57.4%). In contrast, the prevalence of H-Hcy was lower among those deficient in either vitamin B12 (31.1%) or folate (23.2%) alone. Significant associations were identified between the MTHFR C677T and A1298C polymorphisms and elevated serum tHcy concentrations, particularly in individuals homozygous for the T allele. Conversely, the MTRR A66G genotype did not show a significant correlation with tHcy concentrations. Optimal vitamin B12 concentrations significantly modulated the genotypic effect on tHcy concentrations, with individuals having adequate vitamin B12 and folate exhibiting low tHcy concentrations, even among high-risk genotypes (TT). ConclusionsAdequate concentrations of folate and vitamin B12 significantly reduce serum tHcy concentrations and mitigate the genotypic impact on tHcy concentrations, highlighting the potential for targeted nutritional interventions to manage cardiovascular risks associated with H-Hcy.This trial was registered at clinicaltrials.gov as ChiCTR2100051983.

Polymorphism of Folate Metabolism Genes among Ethnic Kazakh Women with Preeclampsia in Kazakhstan: A Descriptive Study.

Preeclampsia is a severe multifactorial complication of pregnancy. Studies found associations between folate metabolism genes' polymorphisms and preeclampsia. However, investigations in this field are limited among Asian populations. Thus, the study's aim was to evaluate the prevalence of methionine synthase (MTR), methionine synthase reductase (MTRR), and methylenetetrahydrofolate reductase (MTHFR) genes' polymorphisms among ethnic Kazakh women with preeclampsia. This was a retrospective study involving 4246 patients' data for the period of 2018-2022. Identification of MTR, MTRR, and MTHFR genes' polymorphism was performed via PR-PCR. Peripheral blood samples were obtained for the analyses. In total, 4246 patients' data of Kazakh ethnicity with preeclampsia at >20 weeks gestational age who had undergone an investigation to identify polymorphisms of the folate metabolism pathway genes for the period of 5 years were included in this study. The most common and prevalent mutation was the MTRR A66G polymorphism: 24.5% of all tested patients with preeclampsia had the MTRR A66G polymorphism. It was highest among the 35-39 age group participants. The second most prevalent was the MTHFR C677T polymorphism: 9% of women with preeclampsia had the MTHFR C677T mutation. It was highest among women aged 30-34. There was a rare association of the MTR A2756G mutation with preeclampsia among the study participants. The identified levels of MTRR A66G and MTHFR C677T polymorphisms among the study participants suggest the importance of evaluating MTRR and MTHFR polymorphisms in women with preeclampsia. The role of the MTR A2756G polymorphism in the development of preeclampsia needs to be further investigated.

GSTP1-A313G genetic polymorphism and the risk of preeclampsia in pregnant women: A study in the northern population of Iran

Preeclampsia or high blood pressure in pregnancy is one of the special disorders during pregnancy. It seems that oxidative stress plays an important role in the occurrence of this disease. The purpose of this study is to investigate the relationship between the A313G polymorphism in exon five of the glutathione S-transferase gene (GSTP1) and the risk of preeclampsia in a case-control study. In this study, blood samples were collected from 70 healthy pregnant women and 70 women with preeclampsia. After genomic DNA extraction, the PCR-RFLP method was performed to check the genotype in GSTP1-A313G and the genotypic frequencies of AA, AG, and GG were determined in all samples. Also, using bioinformatics software, the effect of the above polymorphism on the protein structure was investigated. Statistical analysis for A313G polymorphism showed that AG (OR: 1.1684, 95 % CI: 0.5877–2.3228, p = 0.657) and GG (OR: 1.3793, 95 % CI: 0.3376–5.6359, p = 0.654) genotypes were not associated with risk of preeclampsia in the population of northern Iran. However, bioinformatic analyzes have shown that this polymorphism does have a destructive effect on the protein structure. However, more studies with larger sample sizes are needed to draw firm conclusions.

Clinical Patterns of Sarcoidosis Patients with and without Uveitis: Insights from a Dutch Sarcoidosis Centre

ABSTRACT Purpose Uveitis is a common ocular manifestation in individuals with sarcoidosis, a multisystem inflammatory disorder. This study aimed to explore clinical and genetic factors associated with the presence or absence of uveitis in sarcoidosis patients. Methods Total 625 Dutch sarcoidosis patients were included. Among these, 170 underwent ophthalmic examination, and 61 were diagnosed with uveitis. Demographic and clinical data, including age, gender, race, biopsy status, chest radiography findings, TNF-α inhibitor treatment, and uveitis classification were collected retrospectively from medical records. Genetic data was available for HLA haplotypes, TNF-α G-308A, and BTNL2 G16071A polymorphisms. Results The majority of the patients presented with bilateral uveitis (80.3%). The proportion of women was higher in the uveitis group compared to the non-uveitis group (67.2% and 47.7%; p = 0.014). Pulmonary involvement (chest radiographic stage II-III) was significantly lower in patients with uveitis (36.1% versus 64.2%; p < 0.001). Patients with uveitis were more often treated with TNF-α inhibitors (67.2% versus 29.4%; p < 0.001) and the outcome was better compared with the non-uveitis group, 92% vs 68%, responders (p < 0.012). Uveitis patients treated with TNF-α inhibitors (either adalimumab or infliximab) were more likely to suffer from intermediate or posterior uveitis than anterior uveitis. Genetic analysis identified a significant association between the BTNL2 G16071A GG genotype and uveitis (p = 0.012). Conclusion This study highlights distinctive demographic, clinical and genetic features associated with uveitis in sarcoidosis patients. Ocular sarcoidosis was more prevalent in women. Further research is warranted to explore the implications of these findings for treatment strategies and prognostic assessments.

Docosahexaenoic acid, eicosapentaenoic acid, arachidonic acid, and neural tube defects in Tunisian population.

To determine the effect of maternal status in (plasma and red blood cell) folate, vitamin B12, homocysteine, and vitamin D, as well as their interaction with MTHFR (C677T and A1298C) and MTRR A66G polymorphisms, on maternal plasma docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and arachidonic acid (ARA) levels and the risk of neural tube defects (NTDs). ARA, EPA, and DHA composition was assessed using capillary gas chromatography. ARA and DHA levels were higher in controls than in case mothers for low plasma folate status. For low red blood cell folate status, DHA levels were higher in controls than in case mothers. For high homocysteine levels, ARA and DHA levels were higher in controls than in case mothers. NTD mothers had lower EPA and DHA levels for low vitamin B12 levels. NTD mothers had lower DHA levels for low vitamin D levels. For low plasma folate status, DHA levels in the MTHFR C677T gene and ARA and EPA levels in MTHFR A1298C gene were different among the three genotypes in case mothers. DHA levels in the MTHFR C677T gene were different among the three genotypes in case mothers for both low and high homocysteine levels. For low vitamin B12 levels, ARA and DHA levels were different among the three genotypes of the MTHFR C677T gene in case mothers. In the MTHFR C677T gene, ARA and DHA levels were different among the three genotypes in case mothers for low vitamin D levels. More advanced research is required to verify a suitable biochemical parameter status in relation to the genotypes in pregnant women.

Association of MTHFR (C677T, A1298C) and MTRR A66G polymorphisms with fatty acids profile and risk of neural tube defects.

This study aims to determine if 5,10-methylenetetrahydrofolate reductase (MTHFR C677T and A1298C) and methionine synthase reductase (MTRR A66G) gene polymorphisms were associated with fatty acid (FA) levels in mothers of fetuses with neural tube defects (NTDs) and whether these associations were modified by environmental factors. Plasma FA composition was assessed using capillary gas chromatography. Concentrations of studied FA were compared between 42 mothers of NTDs fetuses and 30 controls as a function of each polymorphism by the Kruskal-Wallis nonparametric test. In MTHFR gene C677T polymorphism, cases with (CT + TT) genotype had lower monounsaturated FAs (MUFA) and omega-3 polyunsaturated FA (n-3 PUFA) levels, but higher omega-6 polyunsaturated FAs (n-6 PUFA) and omega-6 polyunsaturated FAs: omega-3 polyunsaturated FAs (n-6:n-3) ratio levels. In MTRR gene A66G polymorphism, cases with (AG + GG) genotype had lower MUFA levels, but higher PUFA and n-6 PUFA levels. Controls with (AG + GG) genotype had lower n-6 PUFA levels. In MTHFR gene C677T polymorphism, cases with smoking spouses and (CT + TT) genotype had lower MUFA and n-3 PUFA levels, but higher PUFA, n-6 PUFA, and n-6:n-3 ratio levels. Cases with (CT + TT) genotype and who used sauna during pregnancy had lower n-3 PUFA levels. In MTRR gene A66G polymorphism, cases with (AG + GG) genotype and who used sauna during pregnancy had higher PUFA and n-6 PUFA levels. Further research is required to clarify the association of FA metabolism and (MTHFR, MTRR) polymorphisms with NTDs.

Cyclin D1 (G870A) polymorphism and breast cancer risk in an Iranian population

Background and Objective: Cyclins are the key regulator of the cell cycle and their over-expression has been seen in many cancers including breast cancer. Cyclin D1 is an oncoprotein encoded by CCND1 gene located on chromosome 11 (11q) which regulates cell cycle in shifting from G1 to S phase. It’s the main target for steroids and mitogenic growth hormones in breast epithelial cells. This study aimed to evaluate the relationship between Cyclin D1 G870A polymorphism and breast cancer risk in a population in the north of Iran.&#x0D; Methods: Whole blood samples collected from 82 patients with breast cancer and 66 healthy women. DNA was extracted and genotyping was performed by Polymerase Chain Reaction Restriction Fragment Length Polymorphism (PCR-RFLP) technique.&#x0D; Results: Genotypic prevalence of AA, AG, GG genotypes among patients were 40.2%, 35.3% and 24.4% and in controls were 30%, 47%, 23%, respectively. There was no significant difference in CCND1 G870A genotype polymorphism between patients and control group (p=0.32). Also, allelic prevalence of A and G alleles in breast cancer patients were 58% and 42%, in controls were 54% and 46%, respectively. The present study showed that there is no significant association between CCND1 G870A polymorphism with the risk of breast cancer.&#x0D; Conclusion: The results of this study revealed that there is no significant association between CCND1 G870A genetic polymorphism and the risk of breast cancer in the population of the north of Iran. More studies with larger samples of cases and controls would be beneficial.

Thrombosis risk in single- and double-heterozygous carriers of factor V Leiden and prothrombin G20210A in FinnGen and the UK Biobank

AbstractThe factor V Leiden (FVL; rs6025) and prothrombin G20210A (PTGM; rs1799963) polymorphisms are 2 of the most well-studied genetic risk factors for venous thromboembolism (VTE). However, double heterozygosity (DH) for FVL and PTGM remains poorly understood, with previous studies showing marked disagreement regarding thrombosis risk conferred by the DH genotype. Using multidimensional data from the UK Biobank (UKB) and FinnGen biorepositories, we evaluated the clinical impact of DH carrier status across 937 939 individuals. We found that 662 participants (0.07%) were DH carriers. After adjustment for age, sex, and ancestry, DH individuals experienced a markedly elevated risk of VTE compared with wild-type individuals (odds ratio [OR] = 5.24; 95% confidence interval [CI], 4.01-6.84; P = 4.8 × 10−34), which approximated the risk conferred by FVL homozygosity. A secondary analysis restricted to UKB participants (N = 445 144) found that effect size estimates for the DH genotype remained largely unchanged (OR = 4.53; 95% CI, 3.42-5.90; P < 1 × 10−16) after adjustment for commonly cited VTE risk factors, such as body mass index, blood type, and markers of inflammation. In contrast, the DH genotype was not associated with a significantly higher risk of any arterial thrombosis phenotype, including stroke, myocardial infarction, and peripheral artery disease. In summary, we leveraged population-scale genomic data sets to conduct, to our knowledge, the largest study to date on the DH genotype and were able to establish far more precise effect size estimates than previously possible. Our findings indicate that the DH genotype may occur as frequently as FVL homozygosity and may confer a similarly increased risk of VTE.

Thrombophilia genetic mutations and their relation to disease severity among patients with COVID-19.

Patients with COVID-19 infection appear to develop virus-induced hypercoagulability resulting in numerous thrombotic events. The aim of the present study was to determine the relationship between the thrombophilia genes mutations (prothrombin G20210A, factor V Leiden, and methyltetrahydrofolate reductase (MTHFR)) and the severity of COVID-19 patients. Prospective cross-sectional study. One hundred and forty patients (80 adults and 60 children) were included in the current study. They were divided into the severe COVID-19 group and the mild COVID-19 group, with each group comprising 40 adults and 30 children. The patients were assessed for FV R506Q, FV R2H1299R, MTHFR A1298C, MTHFR C677T, and prothrombin gene G20210A polymorphisms. CBC, D-dimer, renal and liver function tests, hs-CRP, ferritin, and LDH were also assessed. Thrombotic events were clinically and radiologically documented. Severe COVID-19 cases were significantly more frequent to have a heterozygous mutation for all the studied genes compared to mild COVID-19 cases (p<0.05 for all). Being mutant to gene FV R506Q carried the highest risk of developing a severe disease course (p<0.0001). Patients with abnormally high D-dimer levels were significantly more frequent to be heterozygous for FV R506Q, FV R2H1299R, and prothrombin gene G20210A (p = 0.006, 0.007, and 0.02, respectively). We concluded that there is an evident relationship between severe COVID-19 and inherited thrombophilia. In the current study, FV R506Q gene mutation carried the highest risk of developing a severe COVID-19 disease course.

Factor V Leiden G1691A, Prothrombin G20210A, and MTHFR C677T Mutations among Sudanese Women with Recurrent Pregnancy Loss

Background: Various factors, such as genetic causes, anatomic abnormalities of the uterus, infectious diseases, coagulative disorders, and endocrinological and immunological diseases, might influence recurrent pregnancy loss (RLP). This study aimed to evaluate the prevalence and frequency of the FII G20210A, FVL G1691A, and MTHFR C677T polymorphisms in Sudanese women with RPL. Methods and Results: This descriptive cross-sectional study involved 100 women with a history of 3 or more RPLs (the case group) and 94 healthy multiparous women without pregnancy complications (the control group). DNA was extracted from peripheral blood samples. The study of the FII G20210A, FVL G1691A, and MTHFR C677T polymorphisms was performed by PCR and RFLP analysis. For the FII G20210A, the genotype distribution in the case group and control group was as follows: GG=97.0%, GA=3.0%, AA=0% and GG=94.0%, GA=0%, AA=0%, respectively. In the case group, the allelic distribution was as follows: G=98.5%, A=1.5%. In the control group, the A allele was absent, and the frequency of the G allele was 100%. For the MTHFR C677T, the genotypic and allelic frequencies in the case group were 97%, 3%, and 0%, respectively, for the CC, CT, and TT genotypes, and 98.5% and 1.5%, respectively, for the C and T alleles. In the control group, the genotype distribution was as follows: CC-100% CT-0%, TT-0%; the T allele was absent, and the frequency of the C allele was 100%. For the FVL G1691A, the genotype distribution in the case group and control group was as follows: GG=92.0%, GA=8.0%, AA=0% and GG=93.6%, GA=6.4%, AA=0%, respectively. For G and A alleles, the frequencies were 96.0% and 4.0%, respectively, for the case group, and 96.8% and 3.2%, respectively, for the control group. Our analysis did not reveal a significant positive association between the MTHFR C677T, FII G20210A, and FVL G1691A polymorphisms and the risk of RPL across the dominant model, multiplicative model, and a comparison of the frequencies of the heterozygous and homozygous dominant genotypes. Conclusion: The research findings suggest that the MTHFR C677T, FVL G1691A, and FII G20210A variants do not significantly contribute to the increased susceptibility to RPL in this specific population of Sudanese women. Continued scientific inquiry is crucial for developing more nuanced and personalized strategies for the diagnosis and prevention of RPL, ultimately improving women's reproductive health.

Clinical and immunological manifestations of gene polymorphisms cytokines in controlled and uncontrolled bronchial asthma

Introduction. Bronchial asthma (BA) is a multifactorial disease, but its pathogenesis in children is based on atopic inflammation, which is what modern therapies are aimed at combating; less attention is paid to factors of nonspecific inflammation, but they also affect the controllability of the pathological process. The regulation of any inflammation is carried out primarily by cytokines, therefore this work is devoted to the study of polymorphisms of genes for cytokines of nonspecific inflammation.Aim. To explore the association between cytokine gene polymorphisms and clinical immunological features of uncontrolled asthma.Materials and methods. We examined 167 children with asthma, who were divided into groups with and without complete disease control, according to the standard of clinical guidelines for asthma. Additionally, mononucleotide substitutions in the cytokine genes were determined: IL4-C589T (rs2243250), IL6-C174G (rs1800795), IL10-G1082A (rs1800896), IlL10-C592A (rs1800872), IL10- C819T (rs1800871), IL12B-A118 8C (rs3212227) , TNFα- G308A (rs1800629), serum cytokine levels: IL4, 5, 6, 7, 8, 9, 10, 18 and TNFα; standard immunogram indicators: subpopulations of lymphocytes, neutrophil phagocytosis and levels of Ig A, M, G, E.Results and discussion. It was determined that each of the clinically significant mononucleotide substitutions forms a unique cytokine and immune profile that is phenotypically realized in the clinical manifestations of the disease. It has been proven that mononucleotide substitutions IL10-C592A, TNFα- G308A contribute to better control with a tendency to milder asthma; children with the IL6-C174G polymorphism experience more severe disease with a tendency toward decreased control. In addition, mononucleotide substitutions in the genes of signaling molecules of the immune system modify atopic inflammation, weakening (IL10-C592A, TNFα- G308A) or enhancing (IL6-C174G) it, which leads to a change (decrease or increase) in the dose of TGCS, respectively.Conclusion. Thus, determination of IL6-C174G (rs1800795), IL10-C592A (rs1800872), TNFα- G308A (rs1800629) polymorphisms in children with ВА helps to identify a risk group for severe and uncontrolled disease, as well as to personalize therapy.

Global DNA Methylation Levels Viz-a-Viz Genetic and Biochemical Variations in One Carbon Metabolic Pathway: An Exploratory Study from North India.

Despite the importance of one carbon metabolic pathway (OCMP) in modulating the DNA methylation process, only a few population-based studies have explored their relationship among healthy individuals. This study aimed to understand the variations in global DNA methylation levels with respect to selected genetic (CBS 844ins68, MTRR A66G, MTR A2756G, and MTHFR C677T polymorphisms) and biochemical (folate, vitamin B12, and homocysteine) markers associated with OCMP among healthy North Indian adults. The study has been conducted among 1095 individuals of either sex (69.5% females), aged 30-75 years. A sample of 5 mL of blood was collected from each participant. Homocysteine, folate, and vitamin B12 levels were determined using the chemiluminescence technique. Restriction digestion was performed for genotyping MTRR A66G, MTR A2756G, and MTHFR C677T polymorphisms and allele-specific PCR amplification for CBS 844ins68 polymorphism. Global DNA methylation levels were analyzed using ELISA-based colorimetric technique. Of the selected genetic and biochemical markers, the mutant MTRR A66G allele was positively associated with global DNA methylation levels. Further, advanced age was inversely associated with methylation levels. MTRR 66GG genotype group was hypermethylated than other genotypes in folate replete and vitamin B12 deficient group (a condition prevalent among vegetarians), suggesting that the G allele may be more efficient than the wild-type allele in such conditions. Global DNA methylation levels appeared to be more influenced by genetic than biochemical factors. MTRR 66G allele may have a selective advantage in vitamin B12 deficient conditions. Further research should be undertaken to understand how genetics affects epigenetic processes.

The effects of genetic polymorphism on toxicity and pharmacokinetics of methotrexate in Egyptian adult patients with leukaemia or lymphoma

Polymorphisms in genes coding folate-metabolising enzymes might alter the pharmacokinetics and sensitivity for methotrexate “MTX”. The aim of the study aimed to investigate the influence of MTHFR C677T, DHFR19 Ins/del, GGH −401 C > T, and MTR A2756G polymorphisms on MTX toxicity and pharmacokinetics in Egyptian patients with Acute lymphoblastic leukaemia (ALL) or Non-Hodgkin lymphoma (NHL). Fifty adult Egyptian patients with ALL and NHL, treated with high dose MTX, were prospectively enrolled in the study. Clinical and biochemical data was collected objectively from medical records after each cycle of MTX. Plasma concentrations of MTX were measured after 72 h of initiation of infusion. Genotyping was done with a PCR-ARMS and PCR-RFLP assays. The MTHFR C677T T variants significantly increased the risk of leukopoenia, whereas the genotype MTHFR 677 C > T TT significantly associated with lymphocytopenia, thrombocytopenia, and anaemia. The genotype GGH-401 TT was significantly correlated with anaemia. Plasma MTX level was significantly higher in patients with MTR A2756G G variants. MTHFR polymorphism played the main role in MTX toxicities. The pharmacokinetics of MTX was affected by MTR polymorphism. GGH mutation was mainly concerned with anaemia. Pharmacogenetic testing are recommended to optimise MTX therapy.