Interleukin-10 Promoter Polymorphisms Research Articles

Interleukin 18 (-137G/C, -607C/A) Polymorphisms as Genetic Biomarkers of Susceptibility to Systematic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown etiology. Several studies have suggested that interleukin-18 (IL-18) is associated with SLE pathogenesis. The genotype distribution of IL-18 promoter polymorphisms differs among ethnic populations. The present study aimed to investigate the correlation between IL-18 polymorphisms at positions -137 and -607 in patients situated in Northeastern Iran. This case-control study examined the prevalence of IL-18 -137C/G and -607C/A polymorphic variants among 95 SLE patients referred to the Department of Rheumatology, who were referred to the general clinics of Ghaem Hospital and Imam Reza Hospital in Mashhad, Iran, were included in the study. In addition, 100 healthy individuals were included in the control group. DNA from whole blood was extracted by the salting-out method using a commercial kit (Biogene, US). Allelic and genotypic frequencies of polymorphisms (-137G/C, -607C/A) in the IL-18 promoter gene were analyzed using a polymerase chain reaction (PCR)-based amplification refractory mutation system (ARMS) method. The results of this study demonstrated that the frequency of SLE patients with the homozygous C/C genotype of the IL-18 promoter gene at position -137 was significantly higher than that of the homozygous G/G genotype (P < 0.001) in normal controls. Furthermore, the polymorphism analysis performed illustrated a significant association between (-137G/C) and (-607C/A) polymorphisms in the IL-18 promoter gene and SLE (P < 0.005). These results indicated that the 607A/A and 137C/C polymorphisms are more prevalent in SLE. Further research involving larger sample sizes from various populations is necessary to elucidate the role of these polymorphisms and the distribution of alleles in SLE patients.

Association of interleukin-18 promoter polymorphism with comorbid conditions of cardiovascular disease

ObjectivesCardiovascular disease (CVD) is one of the most clinically relevant pathologies that remains the largest single contributor to global mortality. It is often associated with more than one comorbid condition, which obscures its clinical outcome. The current study aimed to evaluate the possible association of interleukin-18 (IL-18) promoter polymorphism with comorbid conditions of CVD. MethodsWe used case-control comparison of specific genotypes of three clinically relevant IL-18 polymorphism hotspots, viz. −656 T/G (rs1946519), −607C/A (rs1946518), and −137 G/C (rs187238) with commonly associated comorbid conditions of CVD such as diabetes, hypertension, and dyslipidemia. For this study, whole blood of CVD patients and healthy control subjects were collected in a citrate coated/plain tube. The routine biochemical parameters were estimated in each sample, and DNA samples were extracted for PCR amplification for further sequencing of targeted amplicons using Sanger method. ResultsThe studied biochemical parameters showed a significant increase in CVD patients compared with control individuals. Fasting glucose and glycosylated hemoglobin (HBA1C) showed an increase from 4.82 to 8.6 (p < 0.05) and 4.33 to 8.2 (p < 0.05), respectively. The results showed a statistically significant association with CVD-diabetes and CVD-hypertension group with GG, GC, and CC genotype at IL-18 gene locus, rs187238. On the other hand, the CVD-dyslipidemia group showed a positive association with allele distribution at the same hotspot. In addition, the GG, GT, and TT genotype and G and T allele distribution at rs1946519 locus showed statistically significant association with CVD-diabetes, CVD-hypertension, and CVD-dyslipidemia p compared with control subjects. We also observed a statistically significant association of dyslipidemia with three genotypic combinations viz. (rs1946518 AA, rs1946519 GG, rs187238 GG); (rs1946518 AA, rs1946519 GT, rs187238 GG), and (rs1946518 AA, rs1946519 TT, rs187238 GG). ConclusionsBased on our study, we conclude that IL-18 loci, rs1946519 has a significant association with each studied comorbid condition and can be considered a prognostic marker of CVD and comorbidities. Our results are anticipated to be utilized to launch a significant pharmaco-genomic investigation that could identify patients with comorbidities who are more likely to develop CVD.

Association between Interleukin-6 Promoter Polymorphism (-174 G/C), Serum Interleukin-6 Levels and severity of sepsis

Association between Interleukin-6 Promoter Polymorphism (-174 G/C), Serum Interleukin-6 Levels and severity of sepsis

Association of IL-6 promoter polymorphism hotspots (-174G/C and -572G/C) with cardiovascular disease risk factors.

Cardiovascular disease (CVD) is the leading cause of death globally, despite the recent advancements in clinical research. Early diagnosis of CVD and prevention of future complications are important for the management of CVD. In the present study, we determined the genotypic linkage of interleukin-6 (IL-6) promoters with the clinical, biochemical, and inflammatory markers of CVD in the Saudi population. The study consisted of 89 patients (male and female) with CVD who were admitted at the King Abdulaziz university hospital, Jeddah, Saudi Arabia. The biochemical parameters were evaluated using an automated chemistry analyzer, and inflammatory markers were measured using specific enzyme-linked immunosorbent assay (ELISA) kits. For genotypic analysis, Sanger sequencing was performed. We observed a statistically significant association (p < 0.05) between GG (66.29%), GC (30.34%), and CC (3.37%) genotypes at the -174G/C (rs1800795) hotspot and neopterin levels. However, the genotypes at the -572G/C (rs1800796) hotspot did not show any association with age, gender, obesity, diabetes, hypertension, dyslipidemia, smoking, and coronary artery status. In addition, no significant association was observed with biochemical and inflammatory markers, namely fasting blood sugar, glycated hemoglobin A1c, creatinine, total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, IL-6, and C-reactive protein. The comparison between different possible genotypic groups and CVD risk factors showed a statistically significant (p < 0.05) association between the male gender and HDL with GG, rs1800795 group vs. GC, rs1800796 group. Similarly, neopterin level was also found to be significantly (p < 0.05) associated with the genotypes GC, rs1800795, and GG, rs1800796. Additionally, the male gender (p < 0.01), age (p < 0.05), serum creatinine (p < 0.001), and neopterin (p < 0.05) were found to be significantly associated with GG, rs1800795 + GG, rs1800796, GC, rs1800795 + GC, and rs1800796 GC. The direct association of neopterin level with IL-6 promoter polymorphism at -174G/C (rs1800795) hotspot indicated the role of inflammation in CVD pathogenesis in the Saudi population.

The association between interleukin-6 promoter polymorphisms and rheumatoid arthritis by ethnicity: A meta-analysis of 33 studies

ObjectiveWe performed a meta-analysis to determine the effect Interleukin-6 (IL-6) promoter polymorphism (−174 G>C, −572 G>C, and −597 G>A) have on the development rheumatoid arthritis (RA) by ethnicity. Material and methodsPubMed, EBSCO, LILACS, and Scopus databases were searched for studies exploring the association between any IL6 polymorphisms and RA until November 2018. Genotype distributions were extracted and, depending on the level heterogeneity, determined by the ψ2-based Q test and the Inconsistency Index (I2), fixed-effects or random-effects models were used to calculate pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) for the heterozygous, homozygous, dominant, recessive, and allelic genetic models. ResultsFrom 708 identified publications, 33 were used in this analysis. For the −174 polymorphism, Asians (ORheterozygous=7.57, 95%CI: 2.28–25.14, ORhomozygous=5.84, 95%CI: 2.06–16.56, ORdominant=7.21, 95%CI: 2.30–22.63, ORrecessive=5.04, 95%CI: 1.78–14.28, ORallelic=6.60, 95%CI: 2.26–19.28, p<.05) and Middle East countries (ORheterozygous=2.30, 95%CI: 1.10–4.81, ORdominant=2.27, 95%CI: 1.22–4.22, ORallelic=2.29, 95%CI: 1.24–4.23, p<.05) were associated with a significant risk of developing RA. Whereas, for Latinos, the C-allele was associated with a benefit (ORhomozygous=0.26, 95%CI: .08–.82, ORrecessive=.25, 95%CI: .08–.80, p<.05). For the −572 polymorphism, Asians demonstrated a significant association for the homozygous and recessive genetic models (8 studies, ORhomozygous=1.56, 95%CI: 1.16–2.09, ORrecessive=1.63, 95%CI: 1.08–2.45, p<.05). For the −597 polymorphism, no association was observed. ConclusionsHere, the −174 G>C polymorphism increased the risk of developing RA in Asians and Middle East populations. Interestingly, for Latinos, the polymorphism was associated with a benefit. For the −572 polymorphism, only the Asian population showed an increased risk of developing RA for the CC genotype.

Association between Interleukin-10 promoter polymorphism with type 2 Diabetes mellitus

Type 2 diabetes mellitus is a multifactorial illness triggered by a complicated interplay of various genetic variants with various environmental variables. The quantity of replicated common genetic variants associated with type 2 diabetes mellitus has increased rapidly with the recent genome-wide association (GWA) research. Major health issue in the public are type 2 diabetes mellitus (T2DM) is common throughout the world. Diabetes mellitus incidence is growing and is anticipated to affect 300 million individuals by 2025. Diabetes has been suggested to alter patterns of cytokine expression as an immune-dependent illness. Insulin resistance (IR) is a disease that results in less than anticipated biological impact of a specified insulin concentration. Insulin resistance and insulin secretion decreased are both defined pathophysiology of T2DM. One of the most alarming health issues of the 21st century is the spread of diabetes around the globe. Our goal in this study was to identify the role of IL-10 polymorphism in T2DM patients. The average age of 60 median patients with type 2 diabetes mellitus (31 males and 29 females) +-SD (45.91667 +-16.08799), fasting blood sugar (FBS) is +-SD (184.25 +-57.76387), hypertension (35 positive/25 negative) and 60 non-diabetic controls (32 males and 28 females) is +- SD (47.31667 +-15.13722). The group (T2DM patients and their control) had not a substantial distinction (P=0.33) and in each group (CC, TT, CT) there was a comparison between IL-10 gene polymorphism. T2DM patients and healthy individuals are not associated with the polymorphism of the gene IL-10 (SNP rs 3021097 (C/T). Keywords: Insulin, Diabetes Mellitis Type 2, Polymorphism, Interleukin-10, Genotype frequencies.

Association of interleukin-6 promoter polymorphism with rheumatoid arthritis: a meta-analysis with trial sequential analysis.

The association of interleukin-6 (IL-6) -174G/C (rs1800795) and IL-6 -572G/C (rs1800796) single-nucleotide polymorphism (SNP) with the risk of acquiring rheumatoid arthritis (RA) was inconsistent among previous studies. This paper aims to investigate the association between IL-6 promoter polymorphism with RA in different ethnics. Relevant studies were searched using Medline and Google Search engines; STATA software was used to perform the meta-analysis. Pooled odds ratios (OR) were calculated to estimate the potential genetic associations. Subgroup analysis and sensitivity analysis were applied to explore the sources of heterogeneity. Lastly, we used TSA (trial sequential analysis) software to verify the reliability of meta-analysis results. A total of 18 studies were included, involving 8116 subjects (3820 RA patients and 4296 controls). We found a tendency to associate RA with the IL-6 -174G/C allele in Asians (C vs G: OR = 4.56, 95% CI = 1.85-11.23; P < 0.001); with IL-6 -572G/C genotype or allele frequencies, there was no statistical differences between RA patients and controls (P > 0.05). TSA results indicate that the current meta-analysis can draw conclusions. IL-6-174G/C gene polymorphism were associated with increased risk of RA in Asians, but not in Caucasians. There was no association between IL-6 -572G/C gene polymorphism and the risk of RA. Key Points • Although the association between interleukin-6 (IL-6) promoter polymorphism and rheumatic arthritis (RA) has been discussed in the previous meta-analysis, their conclusions are inconsistent. • In this study, trial sequential analysis (TSA) was introduced into the meta-analysis, and the following two important conclusions were confirmed: (1) IL-6-174G/C gene polymorphism was associated with increased risk of RA in Asians, but not in Caucasians. (2) There was no association between IL-6 -572G/C gene polymorphism and the risk of RA.

Cardiac calcium score in systemic sclerosis.

Cardiac coronary Ca score (CCS), and extra coronary Ca score (ECCS) estimation in asymptomatic systemic sclerosis (SSc) patients and their relation to different disease and patients' variables. The CCS and ECCS were estimated in asymptomatic 20 SSc patients compared to 20 age and sex-matched healthy control using non-contrast cardiac computed tomography. All were applied for cardiac history taking, examination, echocardiography, body mass index (BMI), complete blood picture, erythrocyte sedimentation rate, and lipid profile estimation. The SSc patients were 11 females and 9 males with a mean age of (42.55 ± 9.145) and mean disease duration (12.9 ± 6.774). CCS was reported in 9 (45%) SSc cases and 2 (10%) of the control; (p = 0.013) and was significantly greater in SSc patients (58.4 ± 175.443) than in the control group (0.7 ± 2.25); (p = 0.01). The ECCS was significantly higher in SSc cases (194.45 ± 586.511) than control group (2.8 ± 7.8); (p = 0.001) and reported in 16 (80%) SSc cases and 3 (15%) of controls; (p = 0.000). Limited scleroderma cases had higher scores than diffuse type. Patients with total ca score (> 100) were older (p = 0.016), had longer disease duration (p = 0.001) and greater BMI (p = 0.002). Significant correlation was found between the log-transformed CCS and disease duration, age, BMI, left ventricular mass, and mass index. Systemic sclerosis patients are at increased risk of subclinical cardiovascular disease determined by cardiac Ca scoring as a noninvasive and reliable method. Extra coronary calcification may be an earlier indicator for this. Disease duration is a determinant risk factor for cardiac calcification in SSc. Key Points • Although the association between interleukin-6 (IL-6) promoter polymorphism and rheumatic arthritis (RA) has been discussed in the previous meta-analysis, their conclusions are inconsistent. • Systemic sclerosis patients are at high risk of accelerated atherosclerosis and cardiovascular diseases. Coronary atherosclerosis was previously estimated in SSc patients through coronary angiography. A novel method of assessing coronary artery disease is the coronary calcium score, as determined by multidetector computed tomography, it measures coronary artery calcification that occurs in atherosclerotic plaque. In this study, the cardiac coronary and extra coronary Ca score were evaluated in relation to disease characteristics in asymptomatic SSC patients for early detection of coronary artery disease.

Role of Interleukin-10 Promoter Polymorphisms in Oral Cancer Susceptibility: A Meta-Analysis

Role of interleukin-10 (IL-10) promoter polymorphisms in the risk of oral cancer (OC) remains controversial. The present study aimed to explore the relation between IL10 promoter polymorphisms and the progression of oral cancer by performing meta-analysis. Seven studies with a total of 2141 controls and 1928 cases were included in our analysis. Overall results showed significant associations between IL-10-1082A/G gene polymorphism and OC susceptibility under all five models. However, OC was not significantly related to the IL-10-592A/C or −819 T/C polymorphism (p > 0.05).

Dizygotic Twins with Irritable Bowel Syndrome and Interleukin-6 Promoter Polymorphism (-174 G/C)

Dizygotic Twins with Irritable Bowel Syndrome and Interleukin-6 Promoter Polymorphism (-174 G/C)

Interleukin-10 gene promoter variants and susceptibility to diabetic nephropathy; a meta-analysis

Introduction: Diabetic nephropathy (DN) is a leading cause of chronic kidney disease (CKD) in diabetes patients. There is ample evidence that the inflammatory pathways are central to both diabetes and DN. Several studies that examined the link between the interleukin-10 (IL10) polymorphisms and DN risk yielded conflicting results. Objectives: The purpose of this meta-analysis is to evaluate the associations between IL10 promoter polymorphisms and DN risk. Methods: A bibliographic search was carried out on PubMed, Google scholar and Web of Science from the beginning until July 30, 2020. Association between IL10 promoter variants (-1082 A&gt;G, -819 C&gt;T and -592 C&gt;A) and DN risk were assessed by considering diabetes without nephropathy (DWN) as well as healthy controls. Data were retrieved and the pooled odds ratio (OR) with 95% confidence interval (CI) was calculated. Results: For the IL10 -1082 A&gt; G analysis, a total of 4 studies with DWN controls (682 cases and 529 controls) and 5 studies with healthy controls (1025 cases and 1625 controls) were considered. For the IL10 -819 C&gt; T analysis, a total of three studies with DWN controls (9619 cases and 445 controls) and 5 studies with healthy controls (1005 cases and 1537 controls) were considered. For the IL10 -592 C&gt; T analysis, a total of 5 studies with DWN controls (819 cases and 645 controls) and 5 studies with healthy controls (1005 cases and 1537 controls) were considered. In addition, there was no evidence of publication bias for IL10 promoter variants. No substantial association was observed between IL10 promoter variants and DN risk. Conclusion: Our study signifies that polymorphisms of IL10 -1082 A&gt;G, -819 C&gt;T and -592 C&gt;A are not linked with DN risk.

The Association Between Interleukin-6 Promoter Polymorphisms and Rheumatoid Arthritis by Ethnicity: A Meta-Analysis of 33 Studies.

We performed a meta-analysis to determine the effect Interleukin-6 (IL-6) promoter polymorphism (-174 G>C, -572 G>C, and -597 G>A) have on the development rheumatoid arthritis (RA) by ethnicity. PubMed, EBSCO, LILACS, and Scopus databases were searched for studies exploring the association between any IL6 polymorphisms and RA until November 2018. Genotype distributions were extracted and, depending on the level heterogeneity, determined by the ψ2-based Q test and the Inconsistency Index (I2), fixed-effects or random-effects models were used to calculate pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) for the heterozygous, homozygous, dominant, recessive, and allelic genetic models. From 708 identified publications, 33 were used in this analysis. For the -174 polymorphism, Asians (ORheterozygous=7.57, 95%CI: 2.28-25.14, ORhomozygous=5.84, 95%CI: 2.06-16.56, ORdominant=7.21, 95%CI: 2.30-22.63, ORrecessive=5.04, 95%CI: 1.78-14.28, ORallelic=6.60, 95%CI: 2.26-19.28, p<.05) and Middle East countries (ORheterozygous=2.30, 95%CI: 1.10-4.81, ORdominant=2.27, 95%CI: 1.22-4.22, ORallelic=2.29, 95%CI: 1.24-4.23, p<.05) were associated with a significant risk of developing RA. Whereas, for Latinos, the C-allele was associated with a benefit (ORhomozygous=0.26, 95%CI: .08-.82, ORrecessive=.25, 95%CI: .08-.80, p<.05). For the -572 polymorphism, Asians demonstrated a significant association for the homozygous and recessive genetic models (8 studies, ORhomozygous=1.56, 95%CI: 1.16-2.09, ORrecessive=1.63, 95%CI: 1.08-2.45, p<.05). For the -597 polymorphism, no association was observed. Here, the -174 G>C polymorphism increased the risk of developing RA in Asians and Middle East populations. Interestingly, for Latinos, the polymorphism was associated with a benefit. For the -572 polymorphism, only the Asian population showed an increased risk of developing RA for the CC genotype.

Clinical implications of IL-10 promoter polymorphisms on disease susceptibility in Indian SLE patients.

Single nucleotide polymorphisms in cytokine genes including interleukin-10 have been described to play a vital role in the overall pathogenesis of systemic lupus erythematosus. However, due to a lack of evidence from the Indian population, this study was conducted to analyse the possible influence of interleukin-10 promoter polymorphisms over the disease susceptibility, serum interleukin-10 level and clinical manifestations of the disease in Indian systemic lupus erythematosus patients. In total, 200 systemic lupus erythematosus patients and 201 controls were recruited under this study. Genotyping of interleukin-10 (−1082A/G; −819T/C and −592C/A) polymorphisms was done by direct DNA sequencing and polymerase chain reaction-restriction fragment length polymorphism methods respectively. Serum interleukin-10 levels were measured by multiplex assay. Interleukin-10 −1082G and −592A allele frequencies were significantly increased in systemic lupus erythematosus patients (corrected p value &lt;0.05). Also, combined −1082AG+GG, −819TC+CC and −592CA+AA genotype frequencies were significantly increased in the patient group. A higher trend of association between −1082AG+GG genotype frequency was observed in patients with serositis (odds ratio = 2.7, p = 0.0233, corrected p value = 0.2097). Serum interleukin-10 levels were significantly higher in systemic lupus erythematosus patients (4.3 ± 3.1 pg/ml) than controls (2.6 ± 1.4 pg/ml) ( p &lt; 0.0001). Furthermore, interleukin-10 levels were positively correlated with disease activity ( p = 0.39, p &lt; 0.0001). The frequency of the GCA (−1082, −819, −592) haplotype was significantly higher in systemic lupus erythematosus patients (10.6%) than controls (1.6%) (odds ratio = 5.4, p = 0.0330). Moreover, ACC, GCC and GCA haplotypes were found to be strongly associated with serositis. However, the frequency of the ACC haplotype was significantly higher in patients with neurologic involvement (odds ratio = 14.9, corrected p value &lt;0.001). Thus, interleukin-10 promoter polymorphisms suggest they have a proactive role in increased susceptibility to the disease among Indian systemic lupus erythematosus patients.

Genetic Polymorphisms in IL-10 Promoter Are Associated With Smoking and Prostate Cancer Risk in African Americans.

Even though prostate cancer (PCa) has good prognosis, there is a discrepancy in the risk among ethnic groups, with high morbidity in African American men. Single nucleotide polymorphisms (SNPs) in interleukin 10 (IL-10) have been associated with inflammation and cancer risk. We investigated the association of five SNPs in the IL-10 promoter with clinical features such as Gleason score and smoking. A total of 413 DNA samples were obtained from a nested case-control study of African American males who were genotyped for 5 SNPs utilizing pyrosequencing. Multiple and binary logistic regression models were applied to analyze the clinical and genotypic data. rs12122923 and rs1800871 were associated with PCa risk. Smoking was also found to increase the risk of PCa by 1.6-fold. rs1800893 was found to be associated with lower grades for prostate cancer. IL-10 promoter polymorphisms might be a risk factor for PCa development in smoking subjects and PCa progression.

Association between polymorphisms in interleukin-18 promoter and risk of coronary artery disease: a meta-analysis.

Background: Previous studies have explored associations between interleukin-18 (IL-18) promoter polymorphisms and coronary artery disease (CAD). However, the results were controversial. We conducted a meta-analysis to clarify the association between the two polymorphisms and CAD risk. Methods: We searched English and Chinese databases and calculated the odds ratio (OR) and 95% confidence interval (CI) to estimate whether there are genetic associations between IL-18 promoter polymorphisms and the risk of CAD. All relevant studies were screened and meta-analyzed using STATA 15.0. Results: A total of 15 studies, including 12 studies for -137 G/C and 9 studies for -607 C/A, were identified for the meta-analysis. For -137 G/C, the results showed a significantly reduced risk of CAD in the dominant model (OR = 0.85) and heterozygous model (OR = 0.88) in the overall analysis. However, in subgroup analysis, decreased CAD risks were only observed in Asian populations for heterozygous genetic models. For -607 C/A, the overall OR revealed a reduced risk of CAD in all five genetic models (allelic, OR = 0.78; recessive, OR = 0.75; dominant, OR = 0.68; homozygous, OR = 0.61; heterozygous, OR = 0.72). In subgroup analysis, reduced CAD risk was also found in five genetic models of the Asian population. We also found that the IL-18 polymorphisms were correlated with myocardial infarction (MI) and multivessel (MV) disease. Conclusion: Our results suggested that the -137 polymorphism and -607 polymorphism in the IL-18 promoter were negatively associated with CAD, especially in the Asian population. In addition, some genetic models were correlated with the severity of CAD.

Interleukin-18 Polymorphisms Deficiency Association with Asthma Risk: An Update Meta-analysis.

Growing evidence indicated conflicting results that Interleukin-18 (IL-18) promoter polymorphisms rs1946518 (A-607C), rs187238 (G-137C) and rs549908 (A-105C) were associated with asthma risk. The aim of this study is to comprehensively evaluate the IL-18 polymorphisms and asthma by a systematic review and meta-analysis. A total of 12 studies testing the association between these polymorphisms and asthma were examined (8 studies for A-607C, 8 studies for G-137C, and 4 studies for A-105C) in the update meta-analysis, up to Dec 30, 2017. Summary odds ratios (ORs) and 95% confidence intervals (CI) were used to estimate the strength of association between each polymorphism and asthma using fixed- and random-effects models when appropriate. Heterogeneity and publication bias were evaluated. The meta-analysis results indicated that any allele frequencies of the IL-18 polymorphisms (A-607C, G-137C and A-105C) was not associated with asthma risk (p>0.05). And no statistically significant association was observed between genotype frequencies of these polymorphisms and asthma under different genetic models (p>0.05). Subgroup analysis results were similar to the main analysis by ethnicity, sample size, genotyping methods, matching criteria and quality score. There was no evidence of publication bias. The present meta-analysis suggests that IL-18 polymorphisms (A-607C, G-137C and A-105C) were unlikely to be associated with asthma risk.

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...

The Role of Interleukin-18 Promoter Polymorphisms ( -607 C/A and 137 G/C ) in Determining HCV Clearance or Persistence.

The Role of Interleukin-18 Promoter Polymorphisms ( -607 C/A and 137 G/C ) in Determining HCV Clearance or Persistence.

Impact of interleukin 6 promoter polymorphisms (−174 G > C, −572 G > C and −597 G > A) on plasma IL-6 levels and their influence on the development of DVT: a study from India

ABSTRACTObjectives: To evaluate the association of interleukin 6 (IL-6) levels with deep vein thrombosis (DVT) and to assess the impact of IL-6 promoter polymorphisms (−174G > C, −572G > C and −597G > A) on its plasma levels and their influence in the development of DVT in India.Methods: One hundred DVT patients and 100 age and sex-matched healthy controls were study subjects. IL-6 polymorphisms were identified by polymerase chain reaction-restriction fragment length polymorphism. IL-6 levels were detected by enzyme-linked immunosorbent assay.Results: Significantly raised IL-6 levels were observed in patients as compared to controls. (Patients: 13.73 ± 6.30 pg/ml, Controls: 11.83 ± 4.47 pg/ml, p = 0.014). The prevalence of C allele of −572G > C polymorphism was significantly higher in patients than controls (Patients: 39.5%, Controls: 27.5%, p = 0.011, χ2=6.463). Subjects with GC and CC genotype had significantly higher IL-6 levels than GG genotype (p=<0.001). Patients with GC and CC genotype increased the DVT risk by 1.39 fold (ORa: 1.39, CI: 0.74–2.62) and 2.69 fold (ORa: 2.42, CI: 1.08–6.70), respectively. IL-6 −174G > C and −597G > A polymorphisms were not associated with raised IL-6 levels and nor with thrombotic risk (−174G > C: p = 0.823 χ2=0.369; −597G > A: p = 0.678 χ2=1.08).Conclusion: Our study emphasizes the importance of −572G > C polymorphism in increasing IL-6 levels, thereby showing its significant role in DVT in India. IL-6 −174G > C and −597G > A were neither associated with raised plasma IL-6 levels nor with thrombotic risk. Thus −572G > C polymorphism detection may be one of the connecting links between IL-6 and thrombotic risk in Indian DVT patients.

Interleukin-18 promoter polymorphisms and idiopathic Parkinson disease: an Egyptian study.

Etiology of sporadic Parkinson's disease (PD) is largely unknown. The contribution of genetic factors to the pathogenesis of PD is supported by the demonstration of high concordance in twins, increased risk among relatives of PD patients and existence of familial cases. This study aimed to examine the relation between interleukin 18 (IL-18) gene promoter polymorphisms and idiopathic PD, and its impact on clinical presentation and disease severity. 30 idiopathic PD patients and 15 age- and sex-matched healthy subjects were included. Disease severity was assessed using Unified Parkinson's Disease Rating Scale (UPDRS). Genetic testing for IL-18 gene promoter -607C/A single nucleotide polymorphisms (SNP) was done using real-time polymerase chain reaction (PCR) technique. A raised risk of PD development was found in patients with A/C and C/C genotypes of the site -607C/A (odds ratios = 1.83 and 1.98, respectively). The distribution of the genotypes showed no significant relation to gender or predominant clinical presentation. The age at onset of disease was significantly lower in C/C and A/A genotypes compared to A/C genotype (p = 0.001 and 0.04, respectively). Patients with A/A genotype showed significantly higher mentation score of UPDRS compared to patients with A/C and C/C genotypes (p = 0.003 and p = 0.002, respectively). Polymorphisms of IL-18 gene promoter increase the risk of developing idiopathic PD. The polymorphisms may affect phenotypic expression rather than being a direct cause of idiopathic PD.