IL-10 Gene Promoter Polymorphisms Research Articles

Association of IL-17A and IL-10 Polymorphisms with Juvenile Idiopathic Arthritis in Finnish Children.

To analyze the role of interleukin IL-17A and IL-10 polymorphisms in susceptibility to juvenile idiopathic arthritis (JIA), 98 Finnish children and adolescents with JIA were studied. Data from the 1000 Genomes Project, consisting of 99 healthy Finns, served as the controls. The patients were analyzed for four IL-17A and three IL-10 gene-promoter polymorphisms, and the serum IL-17A, IL-17F, IL-10, and IL-6 levels were determined. The IL-17A rs8193036 variant genotypes (CT/CC) were more common among the patients than controls, especially in those with polyarthritis (OR 1.93, 95% CI 1.11-3.36; p = 0.020). IL-17A rs2275913 minor allele A was more common in patients (OR 1.45, 95% Cl 1.08-1.94; p = 0.014) and especially among patients with oligoarthritis and polyarthritis than the controls (OR 1.61, 95%CI 1.06-2.43; p = 0.024). Carriers of the IL-17A rs4711998 variant genotype (AG/AA) had higher serum IL-17A levels than those with genotype GG. However, carriers of the variant genotypes of IL-17A rs9395767 and rs4711998 appeared to have higher IL-17F levels than those carrying wildtype. IL-10 rs1800896 variant genotypes (TC/CC) were more abundant in patients than in the controls (OR 1.97, 95%CI 1.06-3.70; p = 0.042). Carriers of the IL-10 rs1800896 variant genotypes had lower serum levels of IL-17F than those with wildtype. These data provide preliminary evidence of the roles of IL-17 and IL-10 in the pathogenesis of JIA and its subtypes in the Finnish population. However, the results should be interpreted with caution, as the number of subjects included in this study was limited.

Determination of IL-6 Gene Promoter Polymorphism in Patients with Hepatitis C and Its Impact on RNA Secondary Structure.

Background and Objectives: A polymorphism in the promoter region of the IL-6 gene would influence the level of IL-6 expression in patients with HCV, resulting in a pro-inflammatory response. Few studies have shown the association between -174G>C (rs1800795) and -1363G>T (rs2069827) polymorphisms and HCV infection, and their results have been contradictory. There are no data published in our population to study such an IL-6 stimulus against HCV infection and its impact on RNA secondary structure. Therefore, we isolated human subjects from the province of Punjab, Pakistan. The objective was to screen for IL-6 gene promoter polymorphisms -174G/C and -1363G/T and those correlated with serum concentrations of IL-6 in patients with HCV and compared with a control. Materials and Methods: In conventional PCR, measurement of serum IL-6 by CLIA and statistical analysis were performed to observe the genotype association studies. By integrating bioinformatics and computational tools, our study aimed to provide a comprehensive understanding of how variations in the promoter region of IL-6 may have functional implications on gene expression. Results: The -174G>C and -1363G>T genotypes in the promoter region of patients with HCV were in strong allelic association (Δ = 0.97, p < 0.001). Interestingly, the bioinformatics analysis was well aligned with our experimental data. Conclusions: Based on the data, it can be inferred that IL-6 gene promoter polymorphisms are important in the dysregulation of IL-6 levels in patients with HCV.

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.

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.

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.

Association of IL-10 gene promoter polymorphisms with food allergy susceptibility and serum IL-10 level in a pediatric Caucasian population.

Interleukin 10 has been shown to play a critical role in the regulation of the immune responses in allergic diseases. To investigate if genetic polymorphisms in the promoter region of the IL-10 gene are associated with food allergy (FA) susceptibility in Caucasian pediatric patients with concomitant allergic diseases and IL-10 levels. The single nucleotide polymorphisms (SNPs) at -1082A>G (rs1800896), -819T>C (rs1800871), and -592A>C (rs1800872) of 62 pediatric patients with IgE-mediated FA were analyzed and correlated with clinical parameters, serum IgE and IL-10 levels. The results were compared with those of 92 healthy controls without FA, personal and/or family history of atopy. Analysis and comparison of genotype distributions, allele frequencies, and haplotypes showed that none of the genotypes confers an increased risk of FA. The genotype -1082 AA in FA patients was associated with moderate to severe symptoms of FA, the development of atopic asthma, and higher levels of IL-10. In a linear regression study, we confirmed that the genotype -1082 AA acts as an independent factor for the higher levels of IL-10. A positive association was also observed between -819T/C and -592 A/C SNPs and later onset of FA. Polymorphisms in the promoter region of the IL-10 gene are not associated with FA susceptibility in our cohort. In FA patients, -1082 A/G SNPs seem to influence the production of IL-10, the severity of FA symptoms, and the development of atopic asthma in this population.

Impact of IL-18 gene promoter polymorphisms on renal cell carcinoma occurrence and prognosis in Chinese Han population*

Abstract Objective Genetic polymorphisms in various inflammatory cytokines have been associated with the risk and growth or invasiveness of renal cell carcinoma (RCC). However, the molecular basis of RCC pathogenesis is unclear. The aim of this study was to explore a possible association between two IL-18 gene promoter polymorphisms, -137G/C and -607C/A, and RCC occurrence and prognosis in a Chinese Han population. Methods Chinese Han patients with RCC (n = 175) and age-matched healthy controls (n = 200) were analyzed by single nucleotide polymorphism genotyping during follow-up. Results IL-18-137G allele frequency was significantly higher in patients with lymph node metastasis (Odds ratio [OR], 3.52; 95% confidence interval [CI], 0.97-16.17; P = 0.045). The IL-18-607 CC genotype was associated with distant metastasis (OR, 2.81; 95% CI, 1.35-6.24; P = 0.025). The IL-18-137 G allele was correlated with more advanced tumor stage (OR, 1.83; 95% CI, 1.05-3.72; P = 0.026) and higher tumor grade (OR, 2.23; 95% CI, 0.78-4.12; P = 0.041). The IL-18-607 CC genotype frequency was significantly higher in patients with more advanced cancer stage (OR, 2.92; 95% CI, 1.80-6.87; P = 0.001) and higher tumor grade (OR, 2.21; 95% CI, 1.25-12.25; P = 0.035). The IL-18-607 allele was associated with more advanced cancer stage (OR, 2.47; 95% CI, 1.38-3.83; P = 0.002).Carriers of the GG genotype with the -137G/ C polymorphism had a 2.165-times higher risk of RCC progression than carriers of the GC genotype (Hazard ratio = 2.15, 95% CI, 1.270-3.687). Conclusion The IL-18-137 G allele was correlated with more advanced stage, higher tumor grade, and lymph node metastasis. IL-18 gene promoter polymorphism -137G/C may thus influence the prognosis of RCC patients.

Association of interleukin-10 promoter polymorphisms with serofast state after syphilis treatment

ObjectivesRecent studies suggested that upregulation of anti-inflammatory immune response during early syphilis may be associated with persistence of Treponema pallidum infection despite adequate treatment, resulting in a serofast state. The...

A study of association between regulatory polymorphism in the IL-10 gene promoter region and acute viral hepatitis, and acute liver failure.

The level of inflammatory cytokine Interleukin (IL)-10 is increased in patients infected with hepatitis-related acute liver failure (ALF), and this was thought to be because of the regulatory polymorphism in the IL-10 gene promoter region. The present study was designed to analyze the possible association between IL-10 gene promoter polymorphism and acute viral hepatitis (AVH), and ALF. An attempt was made to quantify IL-10 levels at admission, during the hospital stay, and at the final outcome to study its relationship with liver injury among patients with AVH, ALF, and controls. The study included 40 patients each with ALF and AVH. IL-10 gene promoter polymorphism was detected by the PCR-RFLP method. Quantification of IL-10 was done using commercially available ELISA kits. The individuals with -592 AC, -819 TC, -1082 AA genotypes were found to have a significantly higher risk of ALF whereas those with -592 AA and - 819 CC polymorphism were found to be less susceptible. Individuals with - 819 CC were found to be more susceptible to AVH while those with -592 AA and -819 TT were less susceptible as compared to controls. Mean serum IL-10 at admission was significantly elevated in patients with ALF (38.4±11.3 pg/mL) as compared to patients with AVH (16.7±5.4pg/mL) and control population (8.3±3.6 pg/mL, p < 0.05). Regulatory polymorphism in the IL-10 gene promoter has a possible and significant association with severity and outcome in patients with AVH and ALF. Raised levels of IL-10 could be predictive of prognosis in patients with ALF.

Genetic variations in key inflammatory cytokines exacerbates the risk of diabetic nephropathy by influencing the gene expression

BackgroundDiabetic nephropathy is the single strongest predictor of mortality in patients with diabetes. The development of overt nephropathy involves important inter-individual variations, even after adjusting for potential confounding influences of modifiable and non-modifiable risk factors. Genome-wide transcriptome studies have reported the activation of inflammatory signaling pathways and there is mounting indication of the role of genetic factors. MethodsWe screened nine genetic variations in three cytokine genes (TNF-α, IL-6 and IL-β) in 1326 unrelated subjects comprising of healthy controls (n = 464), type 2 diabetics with nephropathy (DN, n = 448) and type 2 diabetes without nephropathy (T2D, n = 414) by sequence-specific amplification. Functional implication of SNPs was elucidated by correlation studies and relative gene expression using Realtime-Quantitative PCR (RT-qPCR). ResultsIndividual SNP analysis showed highest association of IL-1β rs16944-TT genotype (OR = 3.51, 95%CI = 2.36–5.21, P = 0.001) and TNF-α rs1800629-AA genotype (OR = 2.75, 95% CI = 1.64–4.59, P = 0.001) with T2D and DN respectively. The haplotype frequency showed significant risk of seven combinations among T2D and four combinations among DN subjects. The highest risk of T2D and DN was associated with GGTGAGTTT (OR = 4.25, 95%CI = 3.3–14.20, P = 0.0016) and GACGACCTT (OR = 21.3, 95%CI = 15.1–28.33, P = 0.026) haplotypes respectively. Relative expression by RT-qPCR showed increased cytokine expression in cases as compared to controls. TNF-α expression was increased by more than four-folds (n-fold = 4.43 ± 1.11) in DN. TNF-α, IL-6 and IL-1β transcript levels were significantly modulated by promoter region SNPs. ConclusionsThe present study implicates a strong association between cytokine TNF-α, IL-6 and IL-1β gene promoter polymorphisms and modulation of transcript levels with susceptibility to nephropathy in diabetes subjects.

Genetic Polymorphisms in Cytokine Genes in Colombian Patients with Ocular Toxoplasmosis.

Toxoplasmosis is caused by infection with the protozoan parasite Toxoplasma gondii, which has the capacity to infect all warm-blooded animals worldwide. Toxoplasmosis is a major cause of visual defects in the Colombian population; however, the association between genetic polymorphisms in cytokine genes and susceptibility to ocular toxoplasmosis has not been studied in this population. This work evaluates the associations between polymorphisms in genes coding for the cytokines tumor necrosis factor alpha (TNF-α) (rs1799964, rs1800629, rs1799724, rs1800630, and rs361525), interleukin 1β (IL-1β) (rs16944, rs1143634, and rs1143627), IL-1α (rs1800587), gamma interferon (IFN-γ) (rs2430561), and IL-10 (rs1800896 and rs1800871) and the presence of ocular toxoplasmosis (OT) in a sample of a Colombian population (61 patients with OT and 116 healthy controls). Genotyping was performed with the "dideoxynucleotide (ddNTP) primer extension" technique. Functional-effect predictions of single nucleotide polymorphisms (SNPs) were done by using FuncPred. A polymorphism in the IL-10 gene promoter (-1082G/A) was significantly more prevalent in OT patients than in controls (P = 1.93e-08; odds ratio [OR] = 5.27e+03; 95% confidence interval [CI] = 3.18 to 8.739; Bonferroni correction [BONF] = 3.48e-07). In contrast, haplotype "AG" of the IL-10 gene promoter polymorphisms (rs1800896 and rs1800871) was present at a lower frequency in OT patients (P = 7e-04; OR = 0.10; 95% CI = 0.03 to 0.35). The +874A/T polymorphism of IFN-γ was associated with OT (P = 3.37e-05; OR = 4.2; 95% CI = 2.478 to 7.12; BONF = 6.07e-04). Haplotype "GAG" of the IL-1β gene promoter polymorphisms (rs1143634, rs1143627, and rs16944) appeared to be significantly associated with OT (P = 0.0494). The IL-10, IFN-γ, and IL-1β polymorphisms influence the development of OT in the Colombian population.

Haplotype analysis of IL-10 gene polymorphism in couples with spontaneous abortions and aborted fetuses.

Spontaneous abortion is the loss of pregnancy during an early gestational period. Interleukin-10 is an anti-inflammatory cytokine which plays an important role in successful pregnancy outcome. The aim of the study is to elucidate an association of IL-10 gene promoter polymorphisms (-1082G/A, -819 C/T, -592C/A) in spontaneous abortions from Telangana state of South India. The present population-based retrospective case-control triad study includes a total of 80 case families with spontaneous abortions and 100 control families with medically terminated pregnancies. Peripheral blood from all the couples and fetal tissues of <20weeks of gestation were collected. Genotype analysis was carried out by a standard amplification refractory mutation system-polymerase chain reaction followed by agarose gel electrophoresis. The strength of the association between IL-10 gene promoter polymorphisms and spontaneous abortions were measured by odd ratios and their respective 95% confidence intervals. Haplotype analysis was carried out for the three polymorphisms to establish an association of specific haplotypes with spontaneous abortions. The increased frequency of AA genotype and A allele of -1082G/A, TT genotype and T allele of -819C/T, and AA genotype and A allele of -592C/A was observed in case fetuses and case mothers compared to their respective controls. Haplotype analysis revealed that A-C-A, G-C-A haplotypes in fetuses and haplotypes A-C-C, G-T-C, A-T-A, and G-C-A in mothers were associated with increased risk of spontaneous abortions. IL-10 gene promoter polymorphisms may act as a major genetic regulator in the etiology of spontaneous abortions with maternal genome imprinting effects.

Association of interleukin-10 gene promoter polymorphisms with recurrent miscarriage: a meta-analysis.

The association between IL-10 gene promoter polymorphisms and the risk of recurrent miscarriages (RM) remains controversial. The present meta-analysis was performed to derive a precise estimate of the relationship. We searched the PubMed and EMBASE for studies related to the association between the IL-10 gene polymorphism and the risk of RM. Summary odds ratio (OR) with 95% confidence interval (CI) was estimated to assess the associations. Thirteen studies, including 2047 RM cases and 2055 control samples, were identified. The results showed a significant association between rs1800896, rs1800871 and RM risk (for rs1800896: GA+GG vs AA: OR=1.20, 95% CI=1.04-1.39, P=.02; for rs1800871: CT+TT vs CC: OR=1.64, 95% CI=1.13-2.36, P=.009). No evidence of association was noted between rs1800872 haplotype and RM risk. IL-10 gene promoter polymorphisms, rs1800896 and rs1800871, play a potential role in increasing the risk of RM.

The association of IL-18 gene promoter polymorphisms and the levels of serum IL-18 on the risk of multiple sclerosis

ObjectivesMultiple sclerosis is an inflammatory condition of the central nervous system whose etiology is influenced by immunologic, genetic, and environmental factors. Aim of the present study was to determine if any relation exists between IL-18 −137C/G and −607C/A gene promoter polymorphisms on the individual susceptibility of multiple sclerosis and also to investigate the possible effect of IL-18 activity regarding this kind of polymorphism and MS. Patients and methods113 patients with clinically definite MS and 135 ethnically-matched controls were participated in this study. IL-18 −137C/G and −607C/A gene promoter polymorphisms were analyzed by Sequence Specific Polymerase Chain Reaction (SS-PCR), while levels of serum IL-18 were measured by Enzyme Linked Immunoassay Assay (ELISA) in patients with MS and healthy controls. ResultsOur results showed that the IL-18 −607AA genotype indicated 6 times higher risk in the development of MS (OR=6.883; 3.17–14.96; p<0.001). According to our findings, smoking seems to be an important confounding factor in MS patients with carrying IL-18 −607 AA and CA+AA genotypes. However, no meaningful association was found with IL-18 −137C/G gene promoter polymorphism. ConclusionIn conclusion, we suggest that IL-18 −607C/A gene promoter polymorphism is a major genetic factor for determining individual susceptibility to MS, where smoking status also increases the risk of MS.

Association Between IL-10 Gene Promoter Polymorphisms (-592 A/C, -819 T/C, -1082 A/G) and Susceptibility to HBV Infection in an Iranian Population.

BackgroundIL-10 can play a vital role in immune response against HBV. Three biallelic SNPs from the transcription start site control the transcription of the IL-10 gene. An association between susceptibility to HBV and IL-10 polymorphisms has been suggested in patients with HBV infection.ObjectivesThe present study was designed to study the association between polymorphisms in interleukin-10 (-1082 A/G, -819 T/C and -592 A/C) promoter gene and chronic hepatitis B virus (HBV) infection.Patients and Methods221 chronically infected patients and 200 healthy control subjects were enrolled in the study. Three biallelic (-1082 A/G, -819 T/C and -592 A/C) polymorphisms in the IL-10 promoter gene were determined by PCR-RFLP method.ResultsPersistent HBV infection was associated with IL-10-1082 AG (P = 0.001) and GG (P = 0.004) genotypes and G (P = 0.000) allele. IL-10-819 T/C and -592 A/C genotype and allele frequencies did not show any correlation with the risk of chronic hepatitis B infection.ConclusionsThese results suggest that polymorphisms in interleukin-10 gene promoter influence clinical outcome of HBV infection and susceptibility to HBV infection.

Statistical analysis of the relationship between IL-10 gene promoter polymorphisms and the development of coronary artery disease.

Here, we conducted a case-control study to investigate the association between IL-10 gene polymorphisms and development of CAD in a Chinese population. A total of 220 patients with CAD and 236 control subjects who visited the Zhengzhou People's Hospital between May 2012 and June 2014 were selected for this study. The IL-10-1082A/G and -592A/C polymorphisms were genotyped by polymerase chain reaction coupled with restriction fragment length polymorphism. The chi-squared test revealed a significant difference in the distributions of the IL-10-1082A/G genotypes (χ2 = 6.32, P = 0.04). This data was then statistically analyzed by logistic regression analysis; we observed revealed that the CC genotype of IL-10-1082A/G had a higher risk of CAD in comparison to the AA genotype (OR = 2.09, 95%CI = 1.11-3.97). Moreover, the C allele of IL-10-1082A/G had a 1.39 fold risk of CAD when compared with (OR = 1.39, 95%CI = 1.06-1.82). We did not observe any significant correlations between the IL-10-592A/C genetic variation and susceptibility to CAD. In conclusion, our study suggests that the IL-10-1082A/G genetic variation could influence the development of CAD in a Chinese population.

The Evaluation of IL6 and ESR1 Gene Polymorphisms in Primary Dysmenorrhea

ABSTRACTPrimary dysmenorrhea is the most common gynecological complaint with painful menstrual cramps in pelvis without any pathology. It affects about half of menstruating women, and it causes significant disruption in quality of life. We investigated the association between IL6 gene promoter and ESR1 gene XbaI and PvuII polymorphisms and primary dysmenorrhea. In this case–control study, 152 unrelated young women with primary dysmenorrhea and 150 unrelated healthy age-matched controls participated. Genomic DNA was isolated and IL6 and ESR1 gene polymorphisms were genotyped using PCR-based RFLP assay. The distribution of genotype and allele frequencies of IL6 gene promoter and ESR1 gene XbaI polymorphisms were not statistically different between patients and controls (p > 0.05). However, the genotype and allele frequencies of ESR1 gene PvuII polymorphism showed statistically significant differences between primary dysmenorrhea patients and controls (p = 0.009 and p = 0.021, respectively). Statistically significant associations were also observed between age and married status of primary dysmenorrhea patients and ESR1 gene PvuII polymorphism (p = 0.044 and p = 0.023, respectively). In combined genotype analyses, AG at ESR1 XbaI and TC at ESR1 PvuII loci encoded a p-value of 0.027. Thus, individuals who are heterozygote at both loci have a lower risk of developing primary dysmenorrhea. Our study suggests no strong association between IL6 gene promoter and ESR1 gene XbaI polymorphisms and primary dysmenorrhea in Turkish women. However, ESR1 gene PvuII polymorphism showed statistically significant differences between primary dysmenorrhea patients and controls. The potential association between ESR1 gene PvuII polymorphism and age and married status of dysmenorrhea patients deserves further consideration.

The -137G/C single nucleotide polymorphism in IL-18 gene promoter contributes to tuberculosis susceptibility in Chinese Han population

BackgroundInterleukin (IL) -18 is crucial to host defense against mycobacterial infections. Recent studies have indicated IL-18 gene polymorphisms are associated with susceptibility to several clinical diseases. ObjectiveThe aim of this study is to investigate the association of IL-18 (-137G/C and -607C/A) gene promoter single nucleotide polymorphisms (SNPs) with susceptibility to tuberculosis (TB), and the effects of those SNPs to its protein producing capacity in Chinese Han population. Methods407 TB patients (including 113 children and 294 adults) and 469 healthy volunteers (including 167 children and 302 adults) from Chinese Han population were enrolled. The IL-18 gene promoter polymorphisms at positions of −137 and −607 were determined by sequence specific primer-polymerase chain reaction (SSP-PCR). The IL-18 levels in the supernatants of PBMCs from 46 healthy volunteers were measured by ELISA. ResultsThe gene distribution of IL-18 -137G/C and -607C/A showed none difference between adult and pediatric population. The frequency of IL-18 -137GG genotype was significantly higher in total TB group than that in total healthy control group (79.1% V 69.3%, P<0.01), while the frequencies of GC genotype and C allele were conversely lower (19.2% V 27.9%, P<0.01; 11.3% V 16.7%, P<0.01 respectively). The difference of the -137CC genotype distribution between patients and controls was not observed. At the -607C/A polymorphic site, patient and control groups had a very similar gene distribution. Isolated PBMCs with IL-18 -137GC/CC genotype were able to produce a higher level of IL-18 than those with IL-18 -137GG genotype, either spontaneously or in response to PMA plus calcimycin A23187. ConclusionIL-18 -137G/C polymorphism contributed to TB susceptibility in Chinese Han population. Allele G might be a predisposing gene of TB, while allele C probably plays a role in preventing mycobacterium tuberculosis infection by promoting more vigorous protein expression.

Role of IL-18 Gene Promoter Polymorphisms, Serum IL-18 Levels, and Risk of Hepatitis B Virus-related Liver Disease in the Guangxi Zhuang Population: a Retrospective Case-Control Study.

The aim of this study was to assess the relationship between IL-18 gene polymorphisms and HBV-related diseases and whether these polymorphisms influence its expression in the Guangxi Zhuang population. We enrolled 129 chronic HBV infected (CHB) patients, 86 HBV-related liver cirrhosis (LC) patients and 160 healthy controls in our study. Polymerase chain reaction-restriction fragment length polymorphism methods were used to detect IL-18 gene -607C/A, -137G/C polymorphisms, and an ELISA kit was employed to determine serum IL-18 levels. No correlation was found between the -607C/A polymorphism and risk of HBV-related disease. For the -137G/C polymorphism, the GC genotype and C allele were associated with a significantly lower risk of CHB (95%CI: 0.32-0.95, p=0.034 and 95%CI: 0.35-0.91, p=0.018) and HBV-related LC (95%CI: 0.24-0.89, p=0.022 and 95%CI: 0.28-0.90, p=0.021). A similar decreased risk was also found with the A-607C-137 haplotype. With respect to IL-18 expression, it was significantly lower in both patient groups, but no association was noted between the two polymorphisms in the IL-18 gene and its expression. Our study indicated that the -137C allele in the IL-18 gene may be a protective factor for HBV-related disease, and serum IL-18 level may be inversely associated with CHB and HBV-related LC.