Gene Promoter Polymorphism Research Articles

Relationship between functional Nrf2 gene promoter polymorphism and sperm DNA damage in male infertility

ABSTRACT This study examines the association of the −617 C > A polymorphism in the Nrf2 gene (rs6721961) with male infertility in a Turkish population and determines its functional role in spermatogenesis in correlation with the impact of different levels of DNA damage on the genotypes. A total of 100 infertile men and 100 healthy fertile men were included in the study. Nrf2 genotyping was performed with the PCR-based restriction fragment length gene polymorphism (RFLP-PCR) analysis. According to our results, the Nrf2 CC, CA, and AA genotype distribution frequencies were 58.6%, 38.4%, and 3% in the control group, respectively, and 38%, 48%, and 14% in the infertile men, respectively. The AA genotype was significantly higher in the patient group. In smokers, a significant difference was found in progressive motility values between the genotypes (p = 0.001). Also, sperm progressive motility and concentration decreased significantly in those smokers with the AA genotype; smokers carrying this genotype were also 5.75 times more likely to have oligoasthenozoospermia than those with CC (p < 0.05). There was a significant relationship between the number of cases with high sperm-DNA damage when comparing the frequency of Nrf2 AA genotype carriers with the CC genotype 16.3% vs. 6.9%, respectively (p < 0.001). These results suggest the importance of the Nrf2 gene C > A (rs 6,721,961) polymorphism in the etiology of sperm DNA damage as a risk factor for male infertility. Smokers carrying the AA genotype are more likely to impair seminal parameters through antioxidant mechanisms. Abbreviations: Polymerase chain reaction (PCR)-based restriction fragment length gene polymorphism (RFLP-PCR); reactive oxygen species (ROS); deoxyribonucleic acid (DNA); catalases (CATs); superoxide dismutase (SOD); glutathione peroxidase (GPX); glutathione-S-transferase (GST); Nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2); basic leucine zipper (bZIP); antioxidant response element (ARE); World Health Organization (WHO);normospermia(NS);asthenozoospermia(AS);oligozoospermia(OS);oligoasthenozoospermia (OAS); follicle stimulating hormone (FSH); ultraviolet (UV); low-melting-point agarose (LMA); normal-melting-point agarose (NMA); arbitrary units (AU); total comet score (TCS); A one-way analysis of variance (ANOVA); standard deviation (SD); N-acetyltransferase (NAT2); small non-coding RNAs (ncRNAs); microRNAs (miRNA)

Interleukin-6 gene -174G>C promoter polymorphism reduces the risk of periodontitis in Brazilian populations: A meta-analysis

IntroductionPeriodontitis is a multifactorial host-mediated oral disease caused by microbes. Previous studies suggested that interleukin-6 (IL-6) gene promoter polymorphism (-174G > C) are associated with the risk of periodontitis, although the results were inconclusive. This study investigated the association between IL-6 -174G > C polymorphism and susceptibility to periodontitis. MethodA comprehensive search was conducted in PubMed, EMBASE, Web of Science, and Google Scholar databases to retrieve relevant studies. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the strength of the association between 174G > C polymorphism and the risk of periodontitis. Cochrane Q and I2 statistics were used to measure heterogeneity between studies. Publication bias was estimated using Begg's funnel plots and Egger's test. ResultsOur results showed significant differences in the allelic (C vs. G: OR = 0.82, CI = 0.65–1.03), recessive (CC vs. GC + GG: OR = 0.69, CI = 0.42–1.13), and dominant (GC + CC vs. GG: OR = 0.85, CI = 0.63–1.13) genetic models of the IL6 -174G > C polymorphism and risk of periodontitis. Further, subgroup analysis showed decreased susceptibility to periodontitis associated with IL6 -174 G > C in a Brazilian population (C vs. G: OR = 0.60, CI = 0.41–0.88; GC + CC vs. GG: OR = 0.57, CI = 0.42–0.78) but not in Asian or Caucasian populations. ConclusionThe findings of this study revealed that the IL6 -174 “C" allele is protective against periodontitis in the Brazilian population.

SuPAR: A newer biomarker of systemic chronic inflammation

Migraine is a chronic neurological disorder. Inflammation has a key role in migraine pathophysiology. Urokinase plasminogen activator receptor (uPAR) directly involves in inflammatory conditions by facilitating migration of inflammatory cells to different tissues. The aim of this study was to investigate whether uPAR rs344781, common genetic polymorphism in the uPAR promoter region, might be associated with migraine without aura susceptibility in an Iranian population.We enrolled 103 newly diagnosed patients with migraine and 100 healthy controls. Peripheral blood sample was used for DNA extraction and uPAR rs344781 gene polymorphism was determined. Patients filled HIT-6 as a tool to evaluate headache severity.The genotype frequency of uPAR is significantly different between migraine patients and control subjects. Heterozygote genotype (AG) was statistically more frequent in the patients than the controls (P = 0.001; OR = 2.67, 95% CI = 1.51–4.7). Also G allele was more frequent in the patients. Total HIT-6 score was not significantly different between heterozygote and homozygote patients (55.50 ± 2.22 vs. 49.60 ± 3.68 respectively, P = 0.075).In conclusion, our study showed a significant association between uPAR rs344781 gene promoter polymorphism and migraine without aura susceptibility but not with headache severity.

Functional variant rs17525453 within RAB35 gene promoter is possibly associated with increased risk of Parkinson's disease in Taiwanese population.

Our previous study suggests that upregulated RAB35 is implicated in etiology of Parkinson's disease (PD). We hypothesized that upregulated RAB35 results from single nucleotide polymorphisms (SNPs) in RAB35 gene promoter. We identified SNPs within RAB35 gene promoter by analyzing DNA samples of discovery cohort and validation cohort. SNP rs17525453 within RAB35 gene promoter (T>C at position of -66) was significantly associated with idiopathic PD patients. Compared to normal controls, sporadic PD patients had higher C allele frequency. CC and CT genotype significantly increased risk of PD compared with TT genotype. SNP rs17525453 within RAB35 gene promoter leads to formation of transcription factor TFII-I binding site. Results of EMSA and supershift assay indicated that TFII-I binds to rs17525453 sequence of RAB35 gene promoter. Luciferase reporter assays showed that rs17525453 variant of RAB35 gene promoter possesses an augmented transcriptional activity. Our results suggest that functional variant rs17525453 within RAB35 gene promoter is likely to enhance transcriptional activity and upregulate RAB35 protein, which could lead to increased risk of PD in Taiwanese population.

Association of −819 T/C IL-10 gene promoter polymorphisms with susceptibility to leprosy in South Sumatera Indonesia

Background: The prevalence of leprosy continues to increase, especially in Indonesia, which is one of the endemic areas of leprosy. One cytokine that plays an important role in the pathogenesis of leprosy is IL-10. Mutations in the gene could cause changes in IL-10 gene expression. One of the most common polymorphisms associated with the IL-10 gene is −819 C/T polymorphism, which is could affect the production of IL-10, and thus influence the process of microbial elimination in the development of leprosy. Objective: To determine the association of −819 C/T interleukin-10 promoter gene polymorphism in leprosy patients treated at RSUP Dr. Mohammad Hoesin Palembang. Method: This study was an analytic observational study with a case–control design. Blood from patients who fulfilled the inclusion criteria was taken through venous puncture and stored in EDTA tubes. DNA isolation was carried out with a DNA blood mini kit (QIAamp) and stored at −20 °C. Polymorphism of −819 C/T interleukin-10 promoter gene was measured by PCR-RFLP method, electrophoresis, and visualized under UV light. Results: In the case group, TT genotype frequency distribution was 21%, CT was 22%, and CC was 7%. In the control group, TT genotype frequency distribution was 28%, CT was 18%, and CC was 4%. In the case group, the allele T frequency distribution was 32% and C allele was 18%. In the control group, the T allele frequency distribution was 37% and C allele was 13%. Conclusion: There is no significant association of −819 C/T Interleukin-10 promoter gene polymorphism with susceptibility to leprosy, both in terms of genotypes and alleles of these genes.

Impact of MMP2 rs243865 and MMP3 rs3025058 Polymorphisms on Clinical Findings in Alzheimer's Disease Patients.

Alzheimer's disease (AD) is a chronic neurodegenerative disease of the central nervous system with higher prevalence in elderly people. Despite numerous research studies, the etiopathogenesis of AD remains unclear. Matrix metalloproteinases (MMPs) are endopeptidases involved in the cleavage of extracellular matrix proteins and basement membrane compounds. In the brain, the pathological role of MMPs includes the disruption of the blood-brain barrier leading to the induction of neuroinflammation. Among various MMPs, MMP-2 and MMP-3 belong to candidate molecules related to AD pathology. In our study, we aimed to evaluate the association of MMP2 rs243865 and MMP3 rs3025058 polymorphisms with AD susceptibility and their influence on age at onset and MoCA score in patients from Slovakia. Both MMP gene promoter polymorphisms were genotyped in 171 AD patients and 308 controls by the PCR-RFLP method. No statistically significant differences in the distribution of MMP2 rs243865 (-1306 C>T) and MMP3 rs3025058 (-1171 5A>6A) alleles/genotypes were found between AD patients and the control group. However, correlation with clinical findings revealed later age at disease onset in MMP2 rs243865 CC carriers in the dominant model as compared to T allele carriers (CC vs. CT+TT: 78.44 ± 6.28 vs. 76.36 ± 6.39, p = 0.036). The results of MMP3 rs3025058 analysis revealed that 5A/6A carriers in the overdominant model tended to have earlier age at disease onset as compared to other MMP3 genotype carriers (5A/6A vs. 5A/5A+6A/6A: 76.61 ± 5.88 vs. 78.57 ± 6.79, p = 0.045). In conclusion, our results suggest that MMP2 rs243865 and MMP3 rs3025058 promoter polymorphisms may have influence on age at onset in AD patients.

IL-4, IL-17 and CD163 Immunoexpression and IL-6 Gene Polymorphism in Chronic Hepatitis C Patients and Associated Hepatocellular Carcinoma.

Objective:To assess the expression of IL-4, IL-17 and CD-163 as well as study of IL6-572 C/G gene polymorphism in chronic HCV and HCC on top of HCV. Methods:Sixty HCC specimens and 60 adjacent hepatic tissue with HCV of different grades of necro-inflammation and different stages of fibrosis. In addition to 55 HCV, 60 HCC and 50 healthy venous blood samples for evaluation of IL6-572 C/G gene polymorphism. Results:high expression of IL-4, IL-17 and CD163 in higher grades of activity, late stages of fibrosis and higher degrees of steatosis of HCV. IL-4 and CD163 showed higher expression in advanced grades of HCC, while IL-17 more expressed in lower grades. No significant difference in IL6-572 C/G gene polymorphism among studied groups regarding G/C, G/G, C/C frequencies or G and C allele’s frequencies. Conclusion: IL-4, IL-17 and CD163 were associated with HCV severity. Their expression in HCC suggests their important role in HCC development. Blocking of these proteins may be a good target to control inflammation in HCV and can hinder progression to cirrhosis then to HCC. On the other hand, IL6-572 promoter gene polymorphism is neither associated with HCV infection nor with HCC development and its progression.

Interleukin-10 Gene Promoter Polymorphisms and Susceptibility to Asthma: Systematic Review and Meta-analysis.

Several studies have previously assessed the association betweeninterleukin (IL)-10gene polymorphisms and the risk of asthma, leading to conflicting results. To resolve the incongruent outcomes yielded from different single studies, we conducted the most up-to-date meta-analysis ofthe IL-10gene rs1800896, rs1800871, and rs1800872 single-nucleotide polymorphisms (SNPs) and susceptibility to asthma. A systematic literature search performed until April 2020, and the pooled odds ratio (OR) and their corresponding 95% confidence interval (CI) were calculated to determine the association strength. Thirty articles comprising 5678 asthmatic patients and 6079 controls met the inclusion criteria. No significant association was found between rs1800872 SNP and susceptibility to asthma across all genetic models in the overall and subgroup analyses. The rs1800871 SNP had only significant association with a decreased risk of asthma in Europeans (OR 0.66, CI 0.53-0.82, P < 0.001). However, rs1800896 SNP was significantly associated with a decreased risk of asthma by dominant (OR 0.67, CI 0.50-0.90, P < 0.001) and heterozygote (OR 0.66, CI 0.49-0.88, P < 0.001) models in the overall analysis. Subgroup analyses indicated significant association of rs1800896 SNP by dominant (OR 0.45, CI 0.28-0.72, P < 0.001) and heterozygote (OR 0.43, CI 0.26-0.70, P < 0.001) models in the African population. The IL-10 rs1800896 SNP confers protection against the risk of asthma, especially in Africans. Additionally, rs1800871 SNP has a protective role against asthma in Europeans.

The Association between Interleukin-10 Gene Polymorphisms and Hepatitis B Virus: Evidence in Iran

Background and Aim: Hepatitis B virus (HBV) is a human carcinogenesis agent. Interleukin 10 (IL-10) is a key anti-inflammatory cytokine, and single nucleotide polymorphisms in IL-10 gene promoter are correlated with infections caused by HBV. This research intended to assess the prevalence and genotype of HBV as well as the association between the polymorphisms of -819 and -1082 in the IL-10 gene with HBV in individuals with HBV infection in Qom Province, Iran Methods: In this cross-sectional research, 360 individuals with chronic HBV infection and control group were involved between July 2018 and March 2019. HBV diagnosis was evaluated using ELISA and nested PCR assays. To determine polymorphisms in the IL-10 gene promoter in HBV positive and control samples, an allele-specific polymerase chain reaction technique was employed. Results: The constructed phylogenetic trees for the HBsAg gene revealed that all sequences under study belong to genotype D and also, the majority of HBV samples presented similar sequences to the Iranian samples. Genotype frequencies of TT, TC and CC (polymorphism -819) were 82.2%, 11.6% and 6.1% for patients and 85%, 10.5% and 4.4% in control groups, respectively. Also, frequency of genotypes of AA, AG and GG (polymorphism -1082) were 45%, 43.8% and 11.1% for patients and 42.2%, 46.1% and 11.6% in control groups, respectively. Conclusion: Here, we found no association among IL-10 gene polymorphisms in control and HBV-infected groups. However, more studies about the frequency of chronic HBV infection are necessary to be conducted. *Corresponding Author: Mohsen Zargar; Email: zargar@qom-iau.ac.ir Interleukins-10 Gene Polymorphism and Hepatitis B Virus: Evidence in Iran. Arch Med Lab Sci. 2021;7:1-7 (e7). https://doi.org/10.22037/amls.v7.33557

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.

Gene promoter polymorphisms in boar spermatozoa differing in freezability

Single nucleotide polymorphisms (SNPs) in the 5′-flanking regulatory regions of genes could affect their expression levels. This is a follow-up study aimed to identify polymorphic variants in the 5′-flanking regulatory regions of genes expressed in boar spermatozoa, and to predict the interactions of such variants with transcription factors (TFs) on the gene promoter activity, using bioinformatics. Five and six boars were classified as having good and poor semen freezability (GSF and PSF, respectively) according to post-thaw (PT) assessment of sperm motility and membrane integrity characteristics. The 5′-flanking region sequences of the 14 genes (FOS, NFATC3, EAF2, FGF-14, BAMBI, RAB33B, CKS2, LARS2, SLC25A16, ACADM, CPT2, CCT3, DTD2 and CCDC85A) were PCR amplified and analyzed by Sanger sequencing method. A total of 32 polymorphic variants were identified in the 5′-flanking regions of the genes, including 4 insertion/deletion (indel) polymorphisms, and 8 unknown (novel) SNPs. Multiple sequence alignment analysis revealed a 26-bp indel variant in the 5′-flanking region of the LARS2 gene, which showed greater protein expression in spermatozoa from boars of the PSF group. It was found that 17 polymorphic variants, observed in the differentially expressed (DE) genes, showed significant allele frequency differences between the GSF and PSF groups. Polymorphic variants in the 5′-flanking regulatory regions of the genes contributed to the decrease or increase in the binding affinity for different testis-specific TFs, such as SMAD1, NF-1, FOXMI, RXRA, STAT4 and C/EBPβ. This study provides more insights into the mechanisms responsible for variations in transcriptional activity in promoters of genes expressed in boar spermatozoa. The allelic variants are promising genetic markers for predicting the freezability of boar spermatozoa.

Interleukin-10 (IL-10) 1082 promoter polymorphisms and plasma IL-10 levels in patients with bacterial sepsis.

Background. Interleukin-10 (IL-10) is a multifunctional cytokine which has been seen to play a relevant role in the pathogenesis of sepsis. We examined the association between a single nucleotide polymorphism (SNP) in IL-10-1082G/A in patients with sepsis in Cali city.Methods. A total of 100 patients with sepsis and 50 control subjects were enrolled in this study. Blood samples were collected from all patients in EDTA containing tubes. IL-10-1082G/A gene promoter polymorphism was analyzed by Sequence Specific Polymerase Chain Reaction (SS-PCR), while levels of serum IL-10 were measured by Enzyme Linked Immunoassay Assay (ELISA) in patients with sepsis and healthy controls.Results. AA homozygous genotype was found more frequently in patients (32%), compared with controls (18%). AA homozygous patients showed an increased risk of developing infection by Gram-negative bacteria (OR = 2,875; 95% CI = 1.162-7.113; p = 0.020), and significantly high plasma levels of IL-10 (OR = 4.800, 95% CI 1.652-13.944; p = 0.002). AA homozygous patients high plasma IL-10 levels have greater risk of developing sepsis (63.6%; OR = 4,894; 95% CI: 1,337-17,909; p = 0.002). In this group, Afro-Colombian individuals were overrepresented among the sepsis patients with high plasma IL-10 levels (OR = 1.661; 95% CI: 1.408-1.959; p = 0.036).Conclusion. Our study concluded that AA genotype of IL-10-1082G/A polymorphism is a risk factor for high IL-10 production and development of sepsis by Gram negative bacteria, especially in Afro-Colombian patients.

The relationship between Matrix Metalloproteinase-1 gene promoter (-1607) polymorphism and aggressive periodontitis

The relationship between Matrix Metalloproteinase-1 gene promoter (-1607) polymorphism and aggressive periodontitis

Physiological predictions and the role of IL-10 -819 promoter polymorphism in preeclampsia

Preeclampsia is a multisystem pregnancy-specific syndrome that affects some of pregnancies, which remains a leading cause of maternal and perinatal morbidity and mortality worldwide. Preeclampsia primarily provokes life-threatening, especially to the fetus. The aim of this study was to estimate some physiological and biochemical markers of preeclampsia and investigate the association between IL-10 -819 polymorphism and preeclampsia. A total of 52 pregnant women with preeclampsia and 35 women with normal pregnancy attended the high-risk unit of Erbil Maternity and Pediatric Governmental Hospital, KRG, Iraq, were considered in the present study. During the regular pregnancy check-ups, blood pressure, occurrence of gestational hypertension (early or late onset), preeclampsia, were also documented. Remarkably, serum Urea, Creatinine, Alkaline Phosphatase (ALP) and Mean Platelet Volume (MPV) were significantly increased in preeclampsia patients. In contrast, Direct Bilirubin, Glucose, GPT, GOT and Platelet count were not significant between preeclampsia and control women. Additionally, Mean Arterial Pressure (MAP) and Systolic Blood Pressure (SBP) were significantly elevated. Furthermore, genotyping of IL-10 T-819 C promoter polymorphism was carried out for all participants using a standard Amplification Refractory Mutation System (ARMS) PCR. Genotypic distribution of the control and patient groups were compared with values predicted by Hardy-Weinberg equilibrium using χ2 test. Interestingly, there were significant differences in (IL)-10 (-819) T/C genotype distribution frequency between preeclampsia and control groups. Conclusion The present study suggests that the IL-10 T-819 C gene promoter polymorphism might be a major genetic regulator in the etiology of increased risk of preeclampsia.

Influence of UGT1A1 promoter polymorphism, α-thalassemia and βs haplotype in bilirubin levels and cholelithiasis in a large sickle cell anemia cohort.

Hyperbilirubinemia in patients with sickle cell anemia (SCA) as a result of enhanced erythrocyte destruction, lead to cholelithiasis development in a subset of patients. Evidence suggests that hyperbilirubinemia may be related to genetic variations, such as the UGT1A1 gene promoter polymorphism, which causes Gilbert syndrome (GS). Here, we aimed to determine the frequencies of UGT1A1 promoter alleles, alpha thalassemia, and βS haplotypes and analyze their association with cholelithiasis and bilirubin levels. The UGT1A1 alleles, -3.7 kb alpha thalassemia deletion and βS haplotypes were determined using DNA sequencing and PCR-based assays in 913 patients with SCA. The mean of total and unconjugated bilirubin and the frequency of cholelithiasis in GS patients were higher when compared to those without this condition, regardless of age (P < 0.05). Cumulative analysis demonstrated an early age-at-onset for cholelithiasis in GS genotypes (P < 0.05). Low fetal hemoglobin (HbF) levels and normal alpha thalassemia genotype were related to cholelithiasis development (P > 0.05). However, not cholelithiasis but total and unconjugated bilirubin levels were associated with βS haplotype. These findings confirm in a large cohort that the UGT1A1 polymorphism influences cholelithiasis and hyperbilirubinemia in SCA. HbF and alpha thalassemia also appear as modulators for cholelithiasis risk.

Role of Genetic & Epigenetic Modifications of Low-Density Lipoprotein Receptor (LDLR) Gene in South Indian Acute Myocardial Infraction Patients

Background: Acute Myocardial Infarction (AMI) has conventional risk factors as well as genetic and epigenetic modifications of various genes. Among them gene coding for Low density lipoprotein receptor (LDLR) plays a strategic role in cholesterol homeostasis by eliminating excess LDL-C in blood. LDLR gene promoter polymorphism & DNA methylation status might regulate the expression of genes & its activity. Objective: The present study is designed to evaluate the association of LDLR gene promoter c.-139delCTCCCCCTGC polymorphism & DNA methylation status with Acute Myocardial Infarction (AMI). Methods: 300 angiographically documented MI patients and 300 healthy individuals were recruited for the study. Genomic DNA & RNA was extracted from the whole blood using commercially available assay kits further RNA was converted to cDNA. Biochemical parameters like Total cholesterol, LDL-C, HDL-C, and Triglycerides were estimated using kit methods. Results: The risk factors like systolic, diastolic blood pressures, hypertension, diabetes mellitus, smoking, lipids were found to be significantly higher in AMI patients compared to controls. The genotype and allele distributions of the LDLR c.-139del polymorphism revealed that DD genotype & D-allele were found to be higher among the AMI patients than that of controls. Furthermore, we have observed LDLR gene differential promoter DNA methylation status & mRNA expression. In addition, Insilco analysis have shown that there is a change in TF binding at the Insertion & Deletion sites. Conclusion: The findings of the study suggest that the LDLR c.-139del DD genotype might be used as prognostic marker in risk prediction of Acute Myocardial Infarction.

Interleukin-6 gene -572G&gt;C polymorphism in Egyptian children with idiopathic nephrotic syndrome

ObjectiveTo evaluate the association of -572G > C polymorphism with idiopathic nephrotic syndrome (INS) in children.BackgroundInterleukin 6 (IL-6) gene promoter polymorphisms, including -572G > C polymorphism, have been implicated in INS.Patients and methodsA total of 55 Egyptian children with INS were recruited along with 51 healthy controls. Genotyping for IL-6 gene -572G > C polymorphism was performed by PCR followed by restriction fragment length polymorphism.ResultsGC genotype was more prevalent among patients compared with controls [40 vs. 7.8%, odds ratio (OR)=5.5, P = 0.002], but there was no significant difference between patients and controls regarding CC genotype (9.1 vs. 2%, OR = 5, P = 0.14). Under the dominant model, the pooled GC + CC was more prevalent among patients compared with controls (OR = 5.4, P < 0.001). The distribution of C allele was significantly higher among patients compared with controls (29.1 vs. 5.9%, OR = 5.3, P < 0.001). No significant difference was found between patients and controls regarding the prevalence of any of the alleles or genotypes under codominant, recessive, or dominant models.ConclusionIL-6 gene -572G > C polymorphism confers susceptibility to INS among children, but it has no influence on the response to steroids.

Assessment of the Relationship Between Matrix Metalloproteinase-9 Promoter Gene Polymorphism and Chronic Periodontitis

Objective: To evaluate the association of MMP-9 promoter gene polymorphism in generalized chronic periodontitis patients of an Indian population . Material and Methods: Eighty patients were selected and divided into case and control groups (n=40). Patients included were aged 15-60 years of both genders and diagnosed with chronic periodontitis. Peripheral venous blood samples were obtained, and genomic DNA was isolated by a 'salting out' method. Three possible genotypes were distinguished by three distinct banding patterns, depending on the presence or absence of the Sph I restriction site: CC as allele 1, TT as allele 2, and CT, respectively. Statistical analysis was carried out by applying the Chi-squared test and One-way ANOVA. Results: There was a significant difference in MMP-9 genotypes between Chronic periodontitis patients and healthy controls. Odds ratios for CT genotype and combination of CT and TT genotypes were 3.125 (95% confidence interval, p=0.028) and 3.667 (95% confidence interval, p=0.006) relative to subjects with CC genotype, respectively . Conclusion: The present study revealed an association of MMP-9 (-1562 C/T) gene polymorphism with generalised chronic periodontitis.

Significance of interleukin-31 (IL-31) gene polymorphisms and IL-31 serum level in psoriasis in correlation with pruritus.

IntroductionInterleukin-31 (IL-31) impact on the development and clinical presentation of psoriasis as well as pruritus has not been widely investigated so far.AimTo analyse IL-31 -1066G/A and -2057G/A promoter gene polymorphisms as well as serum IL-31 level and their correlation with severity of psoriasis and pruritus in the population of northern Poland.Material and methodsThe study included 300 psoriasis patients and 186 healthy volunteers. The polymorphisms were analysed using amplified refractory mutation system – polymerase chain reaction (ARMS-PCR) method. Serum levels of IL-31 were measured using the enzyme-linked immunosorbent assay (ELISA) test.ResultsThe -1066 AA genotype of the IL-31 gene was statistically more frequent in patients and it increased the risk of psoriasis (OR = 1.80; p = 0.04). The GG genotype as well as G allele of the IL-31 -2057 gene polymorphism were rarely observed in psoriasis and were associated with a decreased risk of the disease (OR = 0.6, p = 0.007 and OR = 0.7, p = 0.01, respectively). Serum levels of IL-31 were significantly elevated in psoriasis patients (p < 0.000001), however, they did not correlate with the studied polymorphic variants of the IL-31 gene, severity of psoriasis, disease onset, presence of psoriatic arthritis and pruritus intensity.ConclusionsDistinct IL-31 promoter gene polymorphisms may be involved in psoriasis development. It seems that serum concentration of IL-31 may not be a reliable marker of psoriatic pruritus.

Polymorphisms of matrix metalloproteinase-7 and -9 are associated with oral tongue squamous cell carcinoma.

Matrix degradation is an important event in the progression, invasion and metastasis of malignant head and neck lesions. Imbalances, mutations and polymorphisms of MMPs and their inhibitors are observed in several cancer subtypes. The aim of this study was to evaluate the association of the MMP-7 gene promoter (181 A/G) and MMP-9 (-1562 C/T) polymorphisms in oral tongue squamous cell carcinoma (OTSCC). MMP-7 (rs11568818) and MMP-9 (rs3918242) single-nucleotide polymorphisms (SNPs) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis in 71 cases of OTSCC. Normal tissue specimens were obtained from 60 healthy volunteers to serve as the control. The MMP-7 G allele and MMP-9 T allele were more frequent in the OTSCC group than the control group, but only when these two SNPs were taken together was a significant association found with the nodal metastasis of OTSCC (p < 0.001). Based on our results, SNPs in the promoter region of MMP-7 and MMP-9 appear to be associated with greater risk of developing OTSCC, and with a higher propensity to form metastatic tumors. In this respect, molecular studies investigating polymorphisms may be useful in predicting tumor behavior.