Gene Promoter Polymorphism Research Articles

Tumor Necrosis Factor Alpha (TNFα) Gene Promoter Polymorphisms and Haplotypes are Associated with the Febrile Seizure (FS) and TNFα Serum Levels.

Febrile seizure (FS) is a neuroinflammatory disease involving fever-induced seizures affecting children in the early stages of life. TNFα is a pro-inflammatory cytokine reported to be elevated in FS. Specific promoter variants of TNFα could be associated with its elevated cytokine expression and susceptibility to FS. The present study analyzed the association of specific TNFα variants, including TNFα -238 G/A (rs361525), TNFα -308 G/A (rs1800629), and TNFα -376 G/A (rs1800750) promoter polymorphisms, with FS susceptibility, and TNFα serum levels in an Iranian population. Sixty-eight FS patients and 136 controls were enrolled. The SSP-PCR method was utilized to analyze TNFα promoter genotypes. This research also confirmed the genotyping results by sequencing samples of ten patients and normal controls. The GG genotype of -238 SNP was associated with the increased risk of FS [OR = 12.65, 95% CI (2.83-56.60), P-value = 0.0012]. The AA genotype in the-308 region was increased in patients with FS and associated with the disease [OR = 4.62, 95% CI (1.46-14.56), P-value = 0.028]. The increased occurrence of heterozygous AG in the -376 SNP among control groups has been linked to a decreased risk of FS [OR = 0.22, 95% CI (0.11-0.43), P-value = 0.0001]. This study revealed that AGA (-238/ -308/ -376) haplotype with the highest frequency in controls was associated with a decreased risk of FS, while GAA (-238/ -308/ -376) carriers were more susceptible to FS. The current study suggested that TNFα gene promoter variants at rs361525, rs1800629, and rs1800750 could be associated with the susceptibility to FS and altered serum levels of TNFα.

Influence of Vitamin D Status and IL-10 Gene Promoter Polymorphism (rs1800871) on Plasma IL-10 Levels in Apparently Healthy Individuals from Southern India: A Cross-sectional Study

Introduction: Interleukin-10 (IL-10) is a major anti-inflammatory cytokine, which plays an important role in regulating inflammatory responses of the immune system. Changes in IL-10 level and its function can cause an imbalance in immune response, which can be associated with various disease conditions. Aim: To study the influence of vitamin D status and IL-10 gene promoter polymorphism (rs1800871) on circulating IL-10 cytokine levels in apparently healthy South Indian population. Materials and Methods: A cross-sectional study was conducted at the Department of Clinical Pharmacology, JIPMER, Puducherry, India from January 2016 to December 2017. Apparently healthy South Indian volunteers (N=101) of either sex, age more than 18 years, were recruited for the study, after obtaining written informed consent. Serum 25-hydroxy vitamin D and plasma IL-10 levels were measured by using Chemiluminescence and Enzyme Linked Immunosorbent Assay (ELISA), respectively. IL-10 rs1800871 genotyping was performed by Real Time-polymerase Chain Reaction (RT-PCR). Values were expressed as median, Interquartile Range (IQR) and proportions were described as number with percentage. Results: The median serum vitamin D and plasma IL-10 levels observed among the study population were 18.21 ng/ mL IQR, 11.3-23.08 ng/mL) and 9.04pg/mL (IQR, 7.75, 11.34 pg/mL) respectively. The genotype and allele frequencies of rs1800871 were consistent with that of the African, South Asian population of 1000 genome project. Plasma IL-10 levels were not significantly different across genotypes (p-value=0.091), even though the median level among homozygous mutant (TT) volunteers was observed to be less (8.35 pg/mL vs 9.69 pg/mL, 9.83 pg/mL). The correlation between vitamin D and IL-10 levels was observed to be insignificant (p-value=0.143). Conclusion: The present study has reported the rs1800871 genotype frequency, circulating serum vitamin D levels and plasma IL-10 levels in the apparently healthy South Indian population. IL-10 cytokine levels were not significant across the different genotype and vitamin D status groups. No significant correlation was observed between the IL-10 and vitamin D levels among the sample studied.

Screening of single nucleotide polymorphisms in INLT1 gene promoter using Sanger sequencing and analysis of its association with ischemic stroke risk

Screening of single nucleotide polymorphisms in INLT1 gene promoter using Sanger sequencing and analysis of its association with ischemic stroke risk

Association of serotonin transporter promoter polymorphism (5-HTTLPR) with orocecal transit time in irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a multifactorial disorder with altered intestinal motility, secretion, and sensation. Serotonin (5-HT) stimulates gut motility and alters serotonin signaling that may lead to both intestinal and extraintestinal symptoms in IBS. The aim of this study was to examine the association of serotonin transporter gene promoter polymorphism (5-HTTLPR) in IBS with orocecal transit time (OCTT) measured by lactulose hydrogen breath test. This prospective case-control study included 151 IBS patients (mean±SD 37.4±11.6 years, median 36, range 19-68). Ninety-two patients were diarrhea-predominant IBS (D-IBS), 44 constipation-predominant IBS (C-IBS), 15 alternating diarrhea and constipation IBS (M-IBS), and 100 healthy controls (mean±SD 37.2±11.4 years, median 36, range 20-64 years). 5-HTTLPR gene polymorphism was studied by polymerase chain reaction-based method. 5-HT levels were measured by enzyme-linked immunosorbent assay (ELISA). Orocecal transit time (OCTT) was measured by a non-invasive lactulose hydrogen breath test. OCTT was also compared with respect to 5-HTTLPR genotypes in differentIBS phenotypes. Serum serotonin levels were significantly higher in overall IBS patients (152±77 ng/mL, p<0.001), D-IBS (184±76 ng/mL, p<0.001), compared to healthy controls (129±56 ng/mL). There was no difference in 5-HT levels between C-IBS (124±53 ng/mL) and controls. In the case of M-IBS, 5-HT levels were (88±49 ng/mL p<0.05) significantly lower than that of controls. OCTT was significantly shorter in D-IBS patients (95±36 min) as compared to controls (112±41 min). In contrast, C-IBS showed significantly prolonged OCTT (136±54 min). There was a significant difference in OCTT between D-IBS and C-IBS patients (p<0.001). There was no significant association found between OCTT and 5-HTTLPR. Serum serotonin concentrations were increased in D-IBS compared to controls and C-IBS. OCTT was shorter in D-IBS and delayed in C-IBS patients. There was no association of 5-HTLPR polymorphism with OCTT.

Interleukin 10 Gene Promoter Polymorphisms in Patients with Chronic Periodontitis

Background: The anti-inflammatory cytokine, interleukin 10 (IL 10), has a crucial role in periodontal diseases. The gene coding for this cytokine is pleomorphic. In the promoter region of the IL 10 gene, two single nucleotide polymorphisms (SNPs), IL10 1082 and IL 819, have been discovered to affect IL 10 expressions. Objective: To investigate the association of two single nucleotide polymorphisms in the interleukin 10 gene (IL-10-1082 G/A and IL-10-819 C/T) with CPO. Patients and Methods: A total of 64 patients with chronic periodontitis (CPO) and another 40 apparently healthy individuals were enrolled in this case-control study. The IL-10 gene was amplified with two specific sets of primers. Genotyping was achieved by allele-specific polymerase chain reaction (AS-PCR). Results: The frequency of GG, GA and AA genotypes of the SNP IL-10-1082G/A among patients was 48.44%, 42.19% and 9.37% respectively, compared with 32.5%, 35% and 32.5% respectively, among controls. Logistic regression test revealed a significant difference in the frequency of AG (OR=0.19, 95%CI=0.06-0.62, P=0.006) and GG genotype (OR= 0.24, 95%CI=0.07-0.77, p=0.016) between patients and controls. Furthermore, the haplotype block GC (G allele of IL-10-1082G/A and C allele of IL-10-819 C/T) was more common in controls than patients (36.25% vs. 33.44%) with a significant difference (OR= 0.54, 95%CI= 0.29-0.99, p= 0.048). Conclusion: These data suggest that the IL-10-1082 G/A gene polymorphism could be a risk factor for CPO in Iraqi patients.

Interleukin 10 Gene Promoter Polymorphisms in Patients with Chronic Periodontitis

Background: The anti-inflammatory cytokine, interleukin 10 (IL 10), has a crucial role in periodontal diseases. The gene coding for this cytokine is pleomorphic. In the promoter region of the IL 10 gene, two single nucleotide polymorphisms (SNPs), IL10 1082 and IL 819, have been discovered to affect IL 10 expressions.&#x0D; Objective: To investigate the association of two single nucleotide polymorphisms in the interleukin 10 gene (IL-10-1082 G/A and IL-10-819 C/T) with CPO.&#x0D; Patients and Methods: A total of 64 patients with chronic periodontitis (CPO) and another 40 apparently healthy individuals were enrolled in this case-control study. The IL-10 gene was amplified with two specific sets of primers. Genotyping was achieved by allele-specific polymerase chain reaction (AS-PCR).&#x0D; Results: The frequency of GG, GA and AA genotypes of the SNP IL-10-1082G/A among patients was 48.44%, 42.19% and 9.37% respectively, compared with 32.5%, 35% and 32.5% respectively, among controls. Logistic regression test revealed a significant difference in the frequency of AG (OR=0.19, 95%CI=0.06-0.62, P=0.006) and GG genotype (OR= 0.24, 95%CI=0.07-0.77, p=0.016) between patients and controls. Furthermore, the haplotype block GC (G allele of IL-10-1082G/A and C allele of IL-10-819 C/T) was more common in controls than patients (36.25% vs. 33.44%) with a significant difference (OR= 0.54, 95%CI= 0.29-0.99, p= 0.048).&#x0D; Conclusion: These data suggest that the IL-10-1082 G/A gene polymorphism could be a risk factor for CPO in Iraqi patients.

Professional Ballet Dancers’ Balance Ability and Psychological Traits and States: A Longitudinal Pilot Study

Introduction:Professional dancers are committed to dancing despite their injuries and mood changes. Therefore, dancers’ balance ability should be evaluated as an objective indicator of the quality of their dance/dancing ability.Objective:We aimed to examine the relationship between the balance ability of professional ballet dancers and their psychological traits and states by serotonin polymorphism, using pressure and center of gravity sensors.Methods:Five female professional dancers participated in this three-month longitudinal pilot study. The dancers’ stress status was assessed each month on three conditional days to gauge stress conditions. Before and after their standard warm-up exercises, the dancers’ center of gravity was assessed while standing and posing in ballet-specific positions, and psychological questionnaire surveys were conducted to assess the level of anxiety and objective stress. After all observations were completed, serotonin polymorphism was analyzed as one of the psychological traits.Results:All participants possessed the s/s-type (short type) serotonin transporter gene promoter polymorphism, indicating high sensitivity to stress. Their average trait anxiety score was 50.80±8.47. However, all participants were able to be calm, had no injuries, and maintained a stable center of gravity throughout the study period.Conclusion:Throughout the study, from ordinary practice to the time of the approaching ballet performance, the participants maintained stable balance ability regardless of their psychological traits and states of mind. It is unlikely that reactions to stress and psychological traits affected professional dancers’ physicality. Thus, continuous assessment of the balance between mental and physical aspects enhances performance management.

Evaluation of Interleukin-10 -1082 G/A Gene Promoter Polymorphism among Hematologic Malignancies in Children

Evaluation of Interleukin-10 -1082 G/A Gene Promoter Polymorphism among Hematologic Malignancies in Children

IDENTIFICATION OF -2849 IL-10 GENE PROMOTER POLYMORPHISM IN LEPROSY PATIENT

Leprosy is a chronic granulomatous disease. Leprosy is caused by M. leprae. However, not all exposure to M. leprae causes the disease. The condition of the host immune system determines the pathogenesis of leprosy. Interleukin-10 work as a pro- and anti-inflammatory cytokine. Polymorphism in the IL-10 gene promoter affects the amount of IL-10 secretion. The amount of IL-10 secretion determines the body’s response to M. leprae. The purpose of this study was to determine the distribution of -2849 IL-10 gene promoter polymorphism in leprosy patient at RSUP dr. Mohammad Hoesin Palembang. This research is an observational descriptive study with cross sectional design. Polymorphism identification was performed using PCR-RFLP. A total of 50 samples were identified. Most of the leprosy patients at RSUP dr. Mohammad Hoesin for the period January – February were &lt; 50 years old (73.47%), male (66%), MB leprosy (92%), and came from Malay-South Sumatra ethnicity (53.06%). The genotype frequency distribution was GG 93.88%, AG 6.12%, and AA 0%. The frequency of allele G was 96.94% and allele A 3.06%. The majority of leprosy patients at RSUP dr. Mohammad Hoesin had wild-type genotypes.

Cytokine gene variants of TNF-α and IL-10 in the propensity of type 2 diabetes in south Indian population

Chronic inflammation plays an important role in type 2 diabetes mellitus (T2DM), a common endocrinological pro-inflammatory disorder associated with insulin resistance. The objective of the present study is to see individual and combined effect of TNF-α (rs361525, rs1800629) and IL-10 (rs1800872, rs1800896) genes on T2DM susceptibility The genotyping was carried out in 200 T2DM patients and 200 healthy controls by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) using suitable primers. The results shown that TNF-α (GA of rs361525 & rs1800629) and IL-10 (AA of rs1800872 & GA of rs1800896) genes are significantly linked with T2DM development. The presence of AA-GA genotype combination for both TNF-α and IL-10 genes were elevating the risk of T2DM. Moreover, individuals bearing haplotypes AAAA, AACA and AAAG experience the increased risk of T2DM. Furthermore, gene-gene interaction analysis shown that TNF-α (GA of rs361525 & rs1800896) gene redundantly confer 3.4-fold elevated risk for T2DM. In gene-environment interaction, GA of TNF-α −1800896, W/H ratio and TG/HDL ratio were redundantly interacted each other and increase the risk of T2DM by 67-times. In conclusion, our results reveal that there is a significant association between foresaid TNF-α, IL-10 gene promoter polymorphisms and T2DM development. To the best of our knowledge this study is the first of its kind in the literature reporting the epistatic association of TNF-α (rs1800629G/A) gene with TG/HDL ratio and W/H ratio over IL-10 gene polymorphisms for T2DM susceptibility among south Indians.

Interleukin-10-1082A>G (rs1800896) Single Nucleotide Polymorphism is Not a Risk Factor of Chronic Lymphocytic Leukemia in Sudanese Population.

The present study was conducted to examine the association between the IL-10-1082A>G (rs 1800896) polymorphism and risk of Chronic Lymphocytic Leukemia and to assess the correlation between this polymorphism and clinicopathological characters. A case-control study was conducted in Khartoum state, Sudan, during the period from April 2017 to April 2018, involved 110 CLL patients and 80 healthy volunteers as a control group. Physical examination, complete blood count, and immunophenotype were performed in all patients to confirm the diagnosis. Clinical staging such as Rai and Binet were studied. CD38 and ZAP70 were performed by flow cytometry. Blood samples were collected from all participants; DNA was extracted by using ANALYTIKJENA Blood DNA Extraction Kit and analyzed IL-10-1082A>G polymorphism by using Allele Specific-Polymerase Chain Reaction. The statistical analysis was performed using statistical package for social sciences version 23.0 software. Frequency of AA, AG, and GG genotypes was 32.7%, 55.5%, and 11.8% for the patient group and 31.25%, 51.25%, and 17.5% in the control group, respectively. The genotype of IL-10 (-1082A>G) did not associate with susceptibility of CLL in our population. The study showed that the G allele of the IL-10 gene (-1082A>G) is associated with the male sex. However, no significant association was found between -1082A>G genotype and clinicopathological characters. Our results do not support the involvement of the IL-10 -1082A>G promoter gene polymorphism in the increased CLL susceptibility. IL-10-1082G allele (IL-10-1082AG or IL-10-1082GG) was found more frequently in males. Furthermore, no association was observed between the IL-10-1082A>G polymorphism and clinical stages systems as well as established poor prognostic markers. Finally, within the group of patients with CLL, there was no difference in the age at diagnosis and hematological parameters according to genotype distributions.

Genetic study of I kappa B alpha gene promoter polymorphism associated with hepatitis C virus in Egyptian patients

Genetic study of I kappa B alpha gene promoter polymorphism associated with hepatitis C virus in Egyptian patients

P-058: INFLUENCE OF HEME OXYGENASE-I GENE PROMOTER POLYMORPHISM ON THE VASO OCCLUSIVE CRISIS OF SICKLE CELL ANEMIA PATIENTS OF EASTERN INDIA

Purpose: Intravascular hemolysis in sickle cell anemia (SCA) leads to release of heme into the circulation and oxidative stress predisposing to vaso occlusive crisis (VOC). Heme is metabolized by the Heme Oxygenase (HO) enzyme resulting in decrease in oxidative stress. The HO-1 expression is altered by HMOX-1 gene promoter polymorphism. We investigated the role of three HMOX-1 gene polymorphisms [two single nucleotide polymorphisms (SNP), 19(G>C)(rs2071747) and -413A>T(rs2071746), and one dinucleotide (GT)n length polymorphisms (rs3074372)] on VOC in SCA patients of eastern India. Materials and methods: A total of 170 SCA cases (80 mild and 90 severe phenotypes) and 101 healthy controls were considered for this study. Those without incidence of a single pain episode or VOC episode were considered as ‘mild phenotype’ of SCA while those who had three or more acute pain episodes in the last twelve months were considered as ‘severe phenotype’. Genotyping of HMOX-1 (19 G>C) polymorphism was done by ARMS-PCR. Whereas, -413A>T polymorphism and (GT)n repeats were done by DNA sequencing. In HMOX-1 gene promoter, the (GT)n repeats were categorized into three types: first, (GT)n≤27 is noted as ‘Small (S)’ repeats; second, (GT)n=28-32 as ‘Medium (M)’ repeats and third, (GT)n≥33 as ‘Large (L)’ repeats. We categorized repeats into two groups: group-I contains S/S and S/M; whereas, group-II contains L/L, L/M, M/M, and S/L. Genotypes and allele frequency were calculated and compared between cases and controls using SNPstarts. Fisher’s exact test, odds ratio (ORs) and 95% confidence intervals (95% CIs) were calculated by using GraphPad Prism v5.0. The p-value of <0.05 was considered statistically significant. Results: On analysis of HMOX-1 (19G>C) polymorphism (rs2071747) between the mild and severe phenotype of VOC, no significant (p>0.05) variation was found in the allele and genotype distribution. Whereas, in HMOX-1 (-413 A>T) polymorphism, a significantly higher mutant allele (T) (p=0.0185) and genotype were found [AA vs TT (p=0.011) and AA vs AT+TT (p=0.02)] in severe phenotype. However, there is no difference among AA vs AT (p=0.56). On (GT)n repeat analysis, it was found that small repeats were associated with the mild phenotype and large repeats with that of severe phenotype in SCA {Gp-I vs Gp-II [p=0.0014; OR(95%CI)- 3.143 (1.538-6.422)]}. The difference was significant when comparison of severe phenotype SCA was done with controls for (GT)n repeats with larger repeats being commoner in severe phenotype. Conclusion: No difference was noted between mild and severe SCA phenotypes HMOX-1 (19G>C) polymorphism. The prevalence of the small repeat (GT)n was found to be significantly higher in the mild SCA phenotypes and controls. Higher incidence of mutant allele and genotype of HMOX-1(-413T) polymorphism and larger (GT)n repeats in the promoter region of the HMOX-1 gene were associated with the severe phenotypes. Both have a negative effect on the HO-1 enzyme activity leading to increased VOC in severe SCA- phenotype. The capacity of HO-1 enzyme activity appears to be overwhelmed by heme-induced oxidative stress in severe phenotypes and the affected patients suffer more VOC compared to mild SCA phenotypes and controls. The authors do not declare any conflict of interest

Impact of IL-10-1082A\G promoter gene polymorphism and production in lung cancer patients

Lung cancer a deadliest malignant disease , Cytokines play a critical role in regulating host immune response toward cancer and determining the overall fate of tumorigenesis. So this study aimed to investigate the impact gene variation of IL-10 promotor region on production of IL-10 cytokine and their effect on lung cancer outcome. The aim of this study is the detection of IL-10-1082A\G polymorphism and IL-10 serum level with it correlation to progression of disease. A Case-control study was performed to 150 Lung cancer patients patients 54 females and 96 males and matched with age and gender attending to Middle Euphrates Cancer Center in AL-Najaf province with group of 60 healthy individual as control. Blood sample was collected from all patients and control. IL-10 level were measured by enzyme-linked immunosorbent assay (ELISA). Single nucleotide polymorphism detected by ARMS-PCR technique. The result shown that IL-10-1082 G/A significantly (P&lt;0.05) high frequencies of homozygous GG, and G allele carrier in lung cancer patients, in contrast homozygous AA and AG genotype and A allele appear at low frequency with patients. The data showed that genetic variants of the IL-10 affect the IL-10 production and associated with the progression of disease.

Promoter polymorphisms in STK35 and IFT27 genes and their associations with boar sperm freezability

We have shown that STK35 and IFT27 genes are differentially expressed in spermatozoa from boars with good and poor semen freezability (GSF and PSF, respectively). STK35 is a stress-related gene that is implicated in spermatogenesis, whereas IFT27 is a motility-related gene that is mainly involved in intracellular protein transport. In this study we hypothesized that polymorphic variants in the 5′-flanking regulatory regions of STK35 and IFT27 genes could contribute to differences in semen freezability. We also predicted the interactions of the polymorphic variants with transcription factors on the gene promoter activity, using bioinformatics. The 5′-flanking region sequences of the STK35 and IFT27 were PCR amplified and analyzed by Sanger sequencing method. Protein expression in STK35 and IFT27 was determined in pre-freeze (PF) and frozen-thawed (FT) spermatozoa, using western blotting analysis. Sanger sequencing revealed a single nucleotide polymorphism (SNP) rs327863835 (C > T) in STK35 promoter, while two SNPs (rs337563873, A > T; rs331520020, T > C) were detected in IFT27 promoter. STK35 and IFT27 promoter polymorphisms showed significant allele frequency differences between the GSF and PSF groups. Using bioinformatics approaches, we predicted that SNPs resulted in the generation of additional transcription factor binding sites for NFATC2, ELK1 and GR-β, which appeared to enhance or repress the promoter activity of STK35 or IFT27 in either freezability group. Wide variations in STK35 and IFT27 protein expression were observed among the boars, however, significantly higher protein expression was detected in IFT27 in FT spermatozoa of the GSF group. We suggest that the upstream variants, detected in STK35 and IFT27 promoters, might regulate the transcriptional activity of the genes by affecting their potential binding of transcription factors. The results indicate that the allelic variants in STK35 and IFT27 could be considered as potential genetic markers for predicting boar sperm freezability.

Association of IRGM gene promoter polymorphisms with hepatitis B virus infection.

In response to intracellular pathogens, the autophagy gene IRGM plays an essential role in the innate immune response. Various identified IRGM gene risk loci are associated with several diseases but, so far, no study is available that shows the association of IRGM with hepatitis B virus (HBV) infection. We genotyped promoter variants (rs4958842, rs4958843, and rs4958846) of IRGM in HBV infected patients (551) and healthy controls (247) for their role in HBV infection. The genotyping was performed by applying methods developed in our laboratory and various biochemical parameters were assessed applying commercially available kits. Data analysis has shown that the mutant allele A of rs4958842 plays a role in the protection from HBV infection in various genetic models that includes allelic, co-dominant and dominant models with the respective statistical data: allelic (odds ratio [OR] = 0.61; 95% confidence interval [CI] = 0.48-0.78; p = 0.0003), co-dominant (OR = 0.52; 95% CI = 0.38-0.71; p = 0.0008) and dominant (OR = 0.51; 95% CI = 0.38-0.70, p = 0.0004). In chronic hepatitis B (CHB), protective association was observed in the allelic (OR = 0.48; 95% CI = 0.35-0.65, p = 0.0004), co-dominant (OR = 0.38; 95% CI = 0.26-0.54, p = 0.0004) and dominant (OR = 0.38; 95% CI = 0.26-0.54, p = 0.0002) models. Mutant allele C of rs49598843 was associated with the risk of CHB in co-dominant (OR = 1.52; 95% CI = 1.07-2.16, p = 0.04) and dominant (OR = 1.41; 95% CI = 1.00-2.00, p = 0.04) models. The mutant allele C of rs4958846 decreased the risk of HBV infection in allelic (OR = 0.74; 95% CI = 0.59-0.92, p = 0.01), dominant (OR = 0.72; 95% CI = 0.53-0.98, p = 0.05), homozygous (OR = 0.42; 95% CI = 0.24-0.74, p = 0.01) and recessive (OR = 0.42; 95% CI = 0.24-0.74, p = 0.0004) models. However, in the asymptomatic group, it was associated with the increased chance of HBV infection. Haplotypes, ATT (OR = 0.47; 95% CI = 0.33-0.68, p = 0.001) and GTC (OR = 0.68; 95% CI = 0.51-0.92, p = 0.01) protect, whereas GTT (OR = 2.01; 95% CI = 1.55-2.60, p < 0.0001) predisposes the individuals to HBV infection. All of these pvalues mentioned here were obtained after performing Bonferroni correction. In conclusion, our findings revealed that mutant allele A of rs4958842, mutant allele C of rs4958843 and rs4958846 were associated with hepatitis B virus infection in the North Indian population.

Association of matrix metalloproteinase-8 gene promoter polymorphisms with type II diabetes mellitus in Syrian population

ObjectivesMatrix metalloproteinase (MMP)-8 is an enzyme that cleaves extracellular matrix (ECM). It is involved in many diseases' pathology including diabetes mellitus type II (DM). In MMP-8 gene promoter region, there are many polymorphisms with an important role in gene transcription modifying and protein production. -381A/G and -799 C/T SNPs are the most effective polymorphisms, and our study is the first work aimed to evaluate the association between these polymorphisms and DM susceptibility in Syrian population. Designstudy sample included 140 subjects allocated into two groups: H= healthy control, DM= diabetes mellitus. MMP-8 SNPs were determined by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) technique. ResultsThe frequencies of genotypes were significantly different between study groups (adjusted OR =3.621, 95% CI: 1.391-9.428, P = 0.008 for -381GG genotype), and (OR =4.941, 95% CI: 1.640-14.890, P = 0.005 for -799TT genotype). Subjects with minor alleles seem to be more likely to develop DM more than those with the major alleles (OR=2.842, P = 0.01 for G) and (OR =3.995, P = 0.001 for T). ConclusionThis study data has illustrated that there could be a remarkable association between MMP-8 gene promoter polymorphisms -381A/G and -799C/T and diabetic susceptibility in Syrian population.

Autoantibodies to Zinc Transporter 8 and SLC30A8 Genotype in Type 1 Diabetes Childhood: A Pioneering Study in North Africa.

Background Type 1 diabetes (T1D) occurs as a result of insulin deficiency due to destructive lesions of pancreatic β cells. In addition to classical autoantibodies (Abs) to islet cell antigens, antizinc transporter 8 Abs (ZnT8-Ab) have been recently described in T1D. Objective As no data on ZnT8-Ab in Tunisian patients has been reported, we aim to evaluate the relationships between ZnT8-Ab, ZnT8 coding gene (SLC30A8) promoter polymorphism, and T1D risk in newly diagnosed children. Methods ZnT8-Ab were measured in the serum of T1D newly affected children (n = 156) who were admitted to the pediatric department of the Hedi Chaker University Hospital of Sfax. Rs13266634 was genotyped in T1D children and 79 of their first-degree parents. The SPSS software was used to analyze the serological data. Allelic association analysis was conducted with family-based association tests implemented in the FBAT program v1.5.1. Results ZnT8-Ab was detected in 66/156 (42.3%) of T1D newly diagnosed children. Among them, 6 (9%) presented ZnT8-Ab as the only humoral marker. The inclusion of ZnT8-Ab increased the number of Ab-positive patients to 90% and reduced the negative ones by 27%. There was no evidence of any overtransmission of any allele of the rs13266634 C/T polymorphism from parents to affected T1D children, nor of any correlation with any clinical or serological parameter. After the T1D disease onset age adjustment, a significant association was observed with the C allele suggesting that it could have a susceptibility role. Conclusion ZnT8-Ab appears as a relevant diagnostic marker for T1D in Tunisian children, especially at the onset of the disease as teenagers.

Associations between IL-1α, IL-1β, TNFα, and IL-6 variations, and susceptibility to transposition of the great arteries

BackgroundTo evaluate the relationship between IL-1α -889C/T (rs1800587), IL-1β -511C > T (rs16944), TNFα -308G > A (rs1800629), TNFα -238G > A (rs361525), IL-6 -174G > C (rs1800795), and IL-6 -572G > C (rs1800796) polymorphisms and the susceptibility to transposition of the great arteries (TGA).MethodsA prospective analysis was performed on mothers whose newborns were diagnosed as having TGA. For each case of TGA, a mother who gave birth to a healthy neonate in the same period was randomly selected for the control group. The sample size was calculated before planning the study with 80% power and 5% alpha.ResultsTwenty-seven mothers whose newborn had TGA anomalies (group 1) and 27 mothers whose newborn had no TGA (group 2) were included in the study. There were no significant differences between the groups in terms of maternal age, pregestational body mass index, gestational age at birth and infant sex (p > 0.05). The genotype and allele distributions of IL-1α -889C/T (rs1800587), IL-1β -511C > T (rs16944), TNFα -308G > A (rs1800629), TNFα -238G > A (rs361525), IL-6 -174G > C (rs1800795) and IL-6 -572G > C (rs1800796) gene variants were not different between the two groups (p > 0.05).ConclusionsThere was no relation between IL-1α, IL-1β, IL-6, and TNFα promoter gene polymorphisms and TGA occurrence in our study group.Trial registration: This present prospective case–control study was conducted in Baskent University Hospital, Ankara, Turkey, between May 2020 and November 2021. Ethical approval was obtained from the university’s Clinical Research Ethics Commitee (No: KA20/211) in accordance with the Declaration of Helsinki.

Correlation of -475 IL-2 Promoter Gene Polymorphisms and the Levels of Serum IL-2 on the Risk of Multiple Sclerosis.

The aim of present study is to asset the IL-2 promoter gene (SNP -475) as a candidate gene for multiple sclerosis (MS) susceptibility. This study included 70 patients with relapsing - remitting multiple sclerosis (RRMS) and 50 healthy controls. Following the extraction of genomic DNA from peripheral blood, frequency of genotypes and alleles of SNP -475 was calculated using Restriction fragment length polymorphism-polymer chain reaction (RFLP-PCR) and then the results were analyzed statistically. The results revealed the unusual ratio for the heterozygous (AT) was 1.6972 indicating that heterozygous patients were at higher risk of multiple sclerosis than wild homozygous (AA), and homomutant (TT). The results show protective role for - 475 IL-2 promoter among individuals with multiple sclerosis, (O.R: 0.4872; C.I. 95%: 0.1617- 1.4680) and (O.R: 0.9275; C.I. 95%: 0.2476 - 3.4745) for both AA and TT genotypes, respectively. Our results showed that in this population of Iraqi patients, the AT genotype / A allele of -475 IL-2 promoter gene SNP may include attributed factors for MS predisposition.