Association Of Interleukin-6 Gene Polymorphisms Research Articles

Association of interleukin-6 gene polymorphism with susceptibility, neurological deficit and recurrence risk of cerebral infarction

Objective: The aim of this study was to explore if the single nucleotide polymorphism (SNP) of IL-6 was related to the susceptibility, severity of neurological deficit and the recurrence risk of cerebral infarction (CI). Methods: Three hundred and eighty-two patients with CI and 385 healthy controls were selected for IL-6 gene promotor region-174G /C, -572C/G, -597G/A polymorphism by SNaPshot SNP typing. The National Institute of Health Stroke Scale (NIHSS) and Essen Stroke Risk Score (ESRS) were adopted to evaluate the neurological deficit and stroke relapse risk in CI patients. Results: The rs1800796 polymorphism of the IL-6 gene showed a significant correlation with CI, and its GG genotype increased the risk of CI (CG+GG vs CC, P=0. 019). The dominant model of rs1800796 was related to severity of neurological deficit and the recurrence risk of cerebral infarction (CG+GG vs CC. P =0. 048 and P= 0. 019). No association was observed between rs1800795/rs1800797 and CI. Conclusion: IL-6 genetic polymorphism serves as a potential biomarker to determine the susceptibility of CI, neurological deficit and the risk of stroke recurrence.

Association of interleukin-6 gene polymorphisms with the risk of hepatocellular carcinoma: An up-to-date meta-analysis.

Background:This study was aimed to evaluate the association between interleukin-6 (IL-6) gene polymorphisms and the risk of hepatocellular carcinoma (HCC) in a meta-analysis.Methods:A literature search was performed for case-control studies published during May, 1993 to May, 2020 focusing on IL-6 gene polymorphisms (–174G > C, –572G > C, and –597G > A) and HCC susceptibility by using PubMed, Cochrane Database, EMBASE, Web of science, and China National Knowledge Infrastructure. From 128 full-text articles, 11 were included in this meta-analysis. I2 index was used to assess heterogeneity and Newcastle-Ottawa Scale was utilized for quality assessment.Results:For IL-6 –174G > C polymorphism, in codominant (GG vs CC: odds ratios [OR] = 2.78, 95% confidence intervals [CI] = 1.25–6.19, P = .01, I2 = 16%) and recessive (GG+GC vs CC: OR = 2.76, 95% CI = 1.29–5.90, P = .009, I2 = 3%) models, IL-6 –174G>C polymorphism was significantly associated with the risk of HCC. In dominant (GG vs CC+GC: OR = 1.80, 95% CI = 0.92–3.54, P = .09, I2 = 86%) and allele (G vs C: OR = 1.49, 95% CI = 0.95–2.32, P = .08, I2 = 68%) models, IL-6 –174G>C polymorphism had no impact on the risk of HCC. However, in non-Italian Caucasian population, IL-6 –174G>C polymorphism was significantly related to the occurrence of HCC in both dominant (GG vs CC+GC: OR = 3.26, 95% CI = 2.29–4.65, P < .00001, I2 = 0%) and allele (G vs C: OR = 2.48, 95% CI = 1.48–4.15, P = .0006) models. Such correlations also could be observed when healthy individuals were selected as controls. For IL-6 –572G>C and –597G>A polymorphisms, no significant association was observed in all models, regardless of the source of control and population subgroups. No publication bias could be calculated when Begg and Egger tests were employed.Conclusion:This meta-analysis indicated that IL-6 –174G>C polymorphism was significantly related with the risk for HCC, especially in non-Italian Caucasian population. No significant association was observed for the correlation between IL-6 –572G>C and –597G>A polymorphisms and HCC susceptibility.

Association of interleukin-6 gene polymorphisms and glaucoma: Systematic review and meta-analysis.

To conduct a systematic review and meta-analysis to explore the association between IL-6 gene polymorphisms (rs1800795 and rs1524107) and glaucoma. A comprehensive search was performed to select eligible studies regarding IL-6 polymorphisms and glaucoma. The effect sizes in the fixed-effects model were calculated using odds ratios (ORs) with 95% confidence intervals (CIs). Four eligible studies comprising 762 cases and 799 controls were selected for meta-analysis. Regarding the association between the IL-6 rs1800795 polymorphism and glaucoma, those who carried the G/G+G/C genotypes had a non-significant higher risk of glaucoma (OR = 1.29, 95% CI = 0.76-2.19) in the dominant model. However, no obvious association (OR = 0.97, 95% CI = 0.68-1.37) was found for the recessive model (G/G vs G/C+C/C). In the subgroup analysis stratified by ethnicity, no significant associations were observed in populations of Asian or European heritage. Significantly higher glaucoma risks of 15.9 and 99.0 were observed for the dominant (C/C+C/T vs T/T) and recessive (C/C vs C/T+T/T) models, respectively. No statistically significant glaucoma risks were observed for the rs1800795 except rs1524107 polymorphism of IL-6. Further studies with a larger sample size are required to validate the effects of IL-6 polymorphisms on glaucoma risk.

Association between interleukin-6 gene polymorphisms and febrile seizure risk: A meta-analysis.

Background:The association between plasma interleukin-6 (IL-6) levels and the development of febrile seizures (FS) has been reported in multiple previous studies, which showed significantly higher serum IL-6 levels in FS patients than in control patients. However, the mechanism underlying this association remains unclear. One previous study indicated an increased frequency of the −174 GG and −597 GG genotypes in FS patients. Although IL-6 gene polymorphisms may be associated with FS risk, this association remains a matter of debate.ObjectiveConsidering the lack of meta-analyses addressing the possible association between IL-6 gene polymorphisms and the risk of FS, we aimed to perform a meta-analysis to determine the association of IL-6 gene polymorphisms (−572, −174, −597) with the risk of FS.MethodsWe conducted a systematic literature search in the PubMed, EMBASE, and WANFANG databases to collect eligible articles. The associations of IL-6 gene polymorphisms with FS risk were evaluated by calculating the pooled odds ratios and 95% confidence intervals. The dominant, recessive, heterozygous, homozygous, and allele genetic models were used to calculate the combined ORs.ResultsOur meta-analysis showed that IL-6 (−572, −174, −597) polymorphisms were significantly associated with susceptibility to FS.Conclusion:This study provided knowledge regarding the association of IL-6 (572, 174, 597) polymorphisms with susceptibility to FS. The T allele and TT genotype may be associated with an increased risk for FS.

Study of the effect of interleukin-6 gene polymorphism in patients with rheumatoid arthritis

Background Rheumatoid arthritis (RA) is an autoimmune disease that results in a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. Although the clear etiology of RA remains to be elucidated, it is widely accepted that RA is a complex disease, and both environmental and genetic factors can contribute to disease initiation as well as its evolution. The −174G/C polymorphism of interleukin-6 (IL-6) gene has been reported to be responsible for changes in the expression of IL-6, which could in turn lead to greater inflammation and thus affect the clinical status of patients with RA. Aim To determine the association of IL-6 gene polymorphism with patients with RA by studying the frequency of the polymorphism of IL-6 (−174G/C) gene in those patients compared with healthy participants to predict the risk of development of RA. Patients and methods The study was conducted on 200 (150 patients with RA and 50 age-matched and sex-matched healthy control) adult Egyptian patients. IL-6 (−174G/C) genotypes were determined by PCR-restriction fragment length polymorphism analysis. Results The prevalence of polymorphic genotype of GC and CC and C allele was statistically significantly increased in patients with RA than in control (P Conclusion The GC and CC genotype and C allele of IL-6 (−174G/C) may represent a significant genetic molecular marker to predict the risk of RA.

The association of interleukin-6 gene polymorphism and risk of colorectal cancer in Chinese patients

Background: Clinical and experimental data have strongly revealed a vital role of interleukin-6 (IL-6) in the development of both sporadic and colitis-associated colorectal cancer (CRC) development. The aim of our study is to discover the association between CRC risk in Chinese people and one variant (rs1800795) in IL-6 gene which was reported to significantly associate with CRC risk in Caucasian population.

Association of interleukin-6 gene polymorphisms and circulating levels with keloid scars in a Chinese Han population.

The aim of the present study is to explore the effect of IL-6 gene polymorphisms on the development of keloid scar (KS) in the Chinese Han population. Genotyping of IL-6 was performed by the polymerase chain reaction (PCR), followed by restriction fragment length polymorphism assays (PCR-RFLP). Serum level of IL-6 was measured using enzyme-linked immunosorbent assay (ELISA). Results indicated that when the IL-6 -572 CC homozygote genotype was used as the reference group, the GG genotype was found to be associated with a significantly increased risk of KS (GG vs CC: OR = 2.097, 95%CI = 1.100-3.995, P = 0.025). When the IL-6 -572 C allele was used as the reference group, the G allele was found to be associated with significantly increased risk of KS (G vs C: OR = 1.317, 95%CI = 1.002-1.730, P = 0.048). Furthermore, we observed a marked increase in serum IL-6 levels in KS patients with GG genotypes when compared to KS patients harboring the CC genotype. In conclusion, our results suggest that IL-6 gene polymorphism was associated with keloid scars in the southeastern Chinese Han population.

Interleukin-6 gene polymorphisms in Egyptian children with febrile seizures: a case-control study.

BackgroundFebrile seizures are the most common form of childhood seizures. Among pro-inflammatory cytokines, interleukin-6 is the key acute-phase cytokine. To date, only a few studies concerned the association of interleukin-6 gene polymorphisms with febrile seizures.In this study, we aimed to investigate 3 cytokine single-nucleotide polymorphisms situated at positions –174 (G/C), –572 (G/C), and –597 (G/A) in the promoter region of the interleukin-6 gene for the first time in Egyptian children with febrile seizures.MethodsThis was a case–control study included 100 patients with febrile seizure, and matched with age, gender, ethnicity 100 healthy control subjects.Interleukin-6 –174 (G/C), −572 (G/C), and −597 (G/A) polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), while the serum IL6 levels were measured by ELISA method.ResultsCompared to the controls subjects, the frequency of the −174 GG and −597 GG IL6 genotypes were observed to be increased in children with febrile seizures (OR: 4.17; 95 % CI: 1.86–9.49; P <0.01 and OR: 1.96; 95 % CI: 1.06–3.63;P <0.05, respectively). We found a significant positive association between the −597 GG genotype and susceptibility to complex febrile seizures as did the G allele at the same position (OR: 4.2; 95 % CI: 1.4–13.3 for the GG genotype; P <0.01) and (OR: 2.89; 95 % CI: 1.1–7.7 for the G allele; P <0.05 respectively). Our data revealed no association between IL6- genotypes and serum IL6 levels in patients with febrile seizures (P > 0.05).ConclusionIn conclusion, our data brought a novel observation that the presence of a G allele or GG genotype at the −174 and the GG genotype at the −597 positions of the promoter region of the interleukin-6 gene constitute risk factors for developing febrile seizures in Egyptian children. Moreover, we observed a significant positive association between the IL6 –597 GG genotype and susceptibility to complex febrile seizures as did the G allele at the same position. However, we found no association between IL6- genotypes and serum IL6 levels in patients with febrile seizures.

Association of interleukin-6 gene polymorphism (rs1800796) with severity and functional status of osteoarthritis in elderly individuals

Osteoarthritis (OA) is the most prevalent disease of the musculoskeletal system and it has an important genetic component. Despite several reports have shown the involvement of pro-inflammatory cytokine such as interleukin-1β and TNF-α, the role of interleukin-6 (IL-6) in osteoarthritis is still unclear. Thus, this study aimed to analyze the relationship between the single nucleotide polymorphism in the portion −572 of the promoter region of the IL6 gene (SNP −572G/C) with hip and knee OA in the elderly. In this case–control study, 257 physically independent elderly were recruited (case group: 92 individuals with osteoarthritis and control group: 165 individuals with no osteoarthritis). Blood samples were collected from patients for the DNA fragments extraction and amplification by real-time polymerase chain reaction (PCR) by TaqMan system for subsequent genotyping of IL6 gene. The degree of joint damage was assessed by radiographic classification based on the criteria of Kellgren and Lawrence. The functional status was evaluated by Lequesne and WOMAC questionnaires. It was observed that individuals carrying the C allele have lower susceptibility to osteoarthritis (OR=0.51, 95% CI: 0.32–0.80, p=0.004) and less radiological impairment for both hip (Fisher–Freeman–Halton test=4.2 and p=0.04) and knee joints (Fisher–Freeman–Halton test=4.7 and p=0.03). Regarding functional status, individuals carrying the C allele has a lower degree of functional impairment assessed by WOMAC (Mann–Whitney test, p=0.04), although no difference was observed in the Lequesne questionnaire (p>0.05). Additionally, it was observed a marked reduction in IL-6 serum levels in individuals with GC and CC genotypes when compared to individuals harboring GG genotype. In conclusion, the polymorphism −572G/C IL6 is a protective factor for the presence and severity of hip and knee osteoarthritis in the elderly. Further prospective studies with large sample size and methods (e.g. effect of this polymorphism on gene expression, haplotype analysis for IL-6 promoter polymorphism) are needed to validate this study findings.

Association of interleukin-6 gene polymorphism with coronary artery disease: an updated systematic review and cumulative meta-analysis.

Interleukin-6 (IL-6) is an important mediator of atherosclerotic disease and is also associated with coronary artery disease (CAD). The growing evidences suggest that polymorphisms in the IL-6 promoter region influence the progression of CAD. This study was performed to update the systematic results of association of IL-6 gene polymorphisms with CAD. PubMed, Embase, and China Biology Medicine were searched systematically for English and Chinese articles published up to October 31, 2014. Data were extracted using standardized forms. Odds ratios (ORs) with 95 % confidence intervals (CIs) were used to assess the strength of associations. Subgroup analyses were made on ethnicity. A total of 42 studies including 15,145 cases and 21,496 controls were combined in this meta-analysis. IL-6 gene -174G/C polymorphism was associated with an increased risk of CAD (for C allele versus G allele: OR = 1.11, 95 % CI 1.02-1.20; for C/C versus G/G: OR = 1.21, 95 % CI 1.03-1.42; for C/C + C/G versus G/G: OR = 1.14, 95 % CI 1.03-1.27). In the subgroup analyses based on ethnicity, a significant association was found between -174 G/C polymorphism and CAD in Caucasians (for C allele versus G allele: OR = 1.12, 95 % CI 1.03-1.22; for C/C versus G/G: OR = 1.21, 95 % CI 1.02-1.42; for C/C + C/G versus G/G: OR = 1.16, 95 % CI 1.05-1.29). In order to reduce heterogeneity, we removed the outlier studies by a Galbraith plot analysis. As a result, the pooled ORs demonstrated no association of -174G/C polymorphism and CAD (C allele versus G allele: OR = 1.02, 95 % CI 0.97-1.06, p = 0.48; C/C versus G/G: OR = 0.1.03, 95 % CI 0.94-1.13, p = 0.48; C/G + C/C versus G/G: OR = 1.03, 95 % CI 0.96-1.09, p = 0.41; C/C versus C/G + G/G: OR = 1.02, 95 % CI 0.94-1.10, p = 0.70, respectively). The polymorphism of -572 G/C was not associated with CAD significantly (for C allele versus G allele: OR = 0.86, 95 % CI 0.74-1.01; C/C versus G/G: OR = 0.99, 95 % CI 0.43-2.27; C/G + C/C versus G/G: OR = 0.96, 95 % CI 0.80-1.15, respectively). In addition, subgroup analyses showed an association between -572 G/C polymorphism and CAD risk among Chinese (C allele versus G allele: OR = 0.64, 95 % CI 0.48-0.85; C/C versus G/G: OR = 0.38, 95 % CI 0.18-0.81; C/G + C/C versus G/G: OR = 0.47, 95 % CI 0.22-1.00; C/C versus C/G + G/G: OR = 0.58, 95 % CI 0.42-0.81). The C allele of -174G/C polymorphism may associate with increased sensibility to CAD among Caucasians in overall analysis. Nevertheless, the effect is interfered by heterogeneity across the included studies. The C allele of -572G/C polymorphism may decrease the risk of CAD in Chinese.

Association of interleukin-6 gene polymorphisms with hand osteoarthritis and hand osteoporosis

ObjectiveSeveral genes, including IL-6 encoding pro-inflammatory cytokines, are involved in development of osteoarthritis and osteoporosis. The association of radiographic hand osteoarthritis (RHOA) and osteoporosis related phenotypes (RHOP) with polymorphisms in IL-6 has been reported inconsistently. The aim of this study was to examine the association, between RHOA and RHOP and IL-6 polymorphisms in two independent samples. MethodsTwo samples: UK females, including 1440 individuals assessed for RHOA and 3470 assessed for RHOP; Chuvash pedigree including 1499 females and males were assessed for RHOP and RHOA. SNPs were genotyped in the IL-6 genomic region, and used in association analysis with RHOA and RHOP phenotypes. ResultsRHOP phenotypes showed similar heritability estimates in both samples, ranging from 34.5±5.5% to 61.0±2.4%. RHOA in Chuvash had substantially lower heritability estimates compared to twins (e.g. OSP scores: 11.8±2.3% vs. 39.2±4.1%) with much higher prevalence and considerably stronger correlation with age (r=0.811 vs. r=0.505). RHOA in Chuvash sample may be traumatic in nature, caused by heavy and prolonged manual work related to their private farming. There were a number of statistically significant association results with both types of phenotypes. The most consistent result was obtained for JSN in both samples with SNP from the same haploblock. Their combined probability of no association was only p=0.000003. Additionally, there were SNPs common for both RHOA and RHOP. ConclusionsWe have shown polymorphisms in IL_6 are significantly associated with RHOA and hand RHOP in two samples having different ethnicity and lifestyle. Age×environment×genes interaction appears as an important factor of RHOA manifestation and progression.

Interleukin‐6 (IL‐6) –572C→G promoter polymorphism is associated with type 2 diabetes risk in Koreans

Increased levels of inflammatory markers, such as interleukin-6 (IL-6), are associated with type 2 diabetes (T2DM). We investigated the association of IL-6 gene polymorphisms with T2DM and circulating levels of IL-6 in Koreans. A total of 1477 subjects with normal glucose tolerance and 476 T2DM patients were included. We examined IL-6 -174G-->C, -572C-->G, -597G-->A and -1363G-->T promoter region polymorphisms. The main outcome measures were the odds ratio (OR) on T2DM risk and serum concentrations of IL-6 and high-sensitivity C-reactive protein (hs-CRP). Homozygosity for the rare G allele IL-6 -572C-->G was associated with a higher risk of T2DM [OR 1.69 (95%CI 1.11-2.58), P = 0.015]. Serum IL-6 concentrations were associated with the IL-6 -572C-->G genotype in control subjects (G/G: 2.33 +/- 0.41: C/G: 1.53 +/- 0.09: C/C: 1.72 +/- 0.08 ng/l, P = 0.023). Also in the control group, subjects homozygous for the rare G allele showed significantly higher concentrations of hs-CRP than C/C and C/G carriers (G/G: 13.6 +/- 2.9: C/G: 9.2 +/- 0.6: C/C: 7.8 +/- 0.4 mg/l, P = 0.003). The C-allele at the IL-6 -174 SNP was very rare (< 0.01) and -597G-->A and -1363G-->T were monomorphic in this population. Our data demonstrate that the IL-6 -572G/G genotype is associated with higher serum IL-6 and hs-CRP concentrations and with increased risk for T2DM.

Association of IL-6 gene polymorphisms and COPD in a Spanish Population

Interleukin-6 (IL-6) is a potential mediator of systemic effects of Chronic Obstructive Pulmonary Disease (COPD). In the present case-control study we investigated the association of promoter polymorphisms of this gene and COPD in a cohort of 191 patients, smokers without COPD (n=75) and a healthy control population (n=296). Besides spirometry, exercise capacity (6MWD, 6 min walking distance) and body mass index (BMI) were measured in COPD patients. Genotyping of the IL-6 polymorphisms at positions -174, -572 and -597 was performed. The -597G/A and -174G/C polymorphisms were not associated with the disease. However, the -572G/C polymorphism was significantly associated with COPD susceptibility under a dominant model of inheritance. The frequency of the genotypes containing the C allele was significantly lower in the COPD cases (9.9%) compared with the healthy control group (16.9%) and smokers (23.1%), (OR=0.46, p=0.032 and OR=0.28, p=0.012, respectively). The GCG (-597/-572/-174) haplotype was significantly associated with the disease (OR=0.37, p=0.022, COPD cases vs. healthy subjects and OR=0.17, p=0.011, COPD cases vs. smokers). Moreover, a borderline association was also found for the -572G allele and hypoxemia (PaO(2)<60 mmHg) (p=0.05). Our data suggest that the IL-6 -572C allele may confer a diminished risk of developing COPD.

Association of Interleukin-6 Gene Polymorphisms with Bone Mineral Density in Mexican Women

The interleukin-6 gene (IL-6) stimulates osteoclast development; therefore, it has been implicated in osteoporosis. In this study, the association of osteoporosis with three IL-6 gene markers (a CA dinucleotide repeat and two single nucleotide polymorphisms [SNPs]: G-174C and G-572C) was tested in the Mexican population. Population sample was comprised of 70 osteoporotic women, 70 non-osteoporotic women, and 500 subjects from the general population who were genotyped for the IL-6 markers. SNPs were analyzed by real-time PCR using the 5' exonuclease assay, whereas the CA dinucleotide polymorphism was evaluated by PCR and capillary electrophoresis. The allele-phenotype relationship was analyzed with the statistical method STRAT that considered population stratification and the results were adjusted with potential confounders for osteoporosis by a longitudinal multivariate model. We found that the C allele of the G-174C SNP and the A3 allele of the CA polymorphism are associated with increased bone mineral density (BMD) (p<0.0001), whereas the G-572C SNP is not (p=0.19). In concordance, subjects heterozygous for the A3 allele have higher BMD and T score average values (90.75% and -0.87, respectively) than those who did not present any A3 allele (81.4% and -1.45, respectively). Likewise, subjects with the CC genotype of the G-174 SNP have higher BMD (96.5%) and T score average value (-0.33) than those bearing the CG or GG genotype (lumbar BMD, 88.5 and 79.98%, respectively; T score: -1.07 and -1.75, respectively). The CA repeat and the G-174C SNP of the IL-6 gene may become useful markers for osteoporosis in the Mexican population.

No association of interleukin-6 gene polymorphism (-174 G/C) with premature coronary artery disease in a Turkish cohort

Interleukin-6 (IL-6) may contribute to the inflammatory response by activating endothelial cells and stimulating the synthesis of fibrinogen. It might thus be important in the pathogenesis of inflammation associated with coronary artery disease (CAD). Several studies suggested that the -174 C allele was associated with an increased prevalence of coronary heart disease. The aim of this study was to investigate further the association of the IL-6 -174 G/C allele status with premature CAD. A total of 120 patients and 105 controls were included in the study. The IL-6 -174 G/C polymorphism was genotyped using PCR-restriction fragment length polymorphism. The genotype distribution of the -174 G/C polymorphism was not different in premature CAD patients (GG: 53%; GC: 42.6%; CC: 4.3%) and controls (GG: 54.3%; GC: 39%; CC: 6.7%) (P=0.72). The prevalence of the C allele was 25.6% in patients and 26.1% in controls. By multiple regression analysis, family history, smoking, diabetes, and hypertension were independent risk factors of premature CAD, but not IL-6 genotype. We conclude that the IL-6 -174 G/C polymorphism is not associated with the risk of premature CAD, and does not contribute to cardiovascular risk stratification.

We-P11:190 Association of interleukin-6 gene polymorphism with essential hypertension in tatars from Russia

We-P11:190 Association of interleukin-6 gene polymorphism with essential hypertension in tatars from Russia

No association of interleukin-6 gene polymorphism (−174 G/C) with myocardial infarction or traditional cardiovascular risk factors

Background: Recently, a polymorphism at position −174 (G>C) of the interleukin-6 (IL-6) promoter was found to be associated with an increased prevalence of myocardial infarction (MI). The aim of the present study was to further investigate the association of the IL-6 −174 G/C allele status with specific end organ damage, i.e. myocardial infarction in large population-based samples. Methods: Individuals from two Bavarian samples of MI patients (total n=1322) and the population-based Augsburg MONICA survey (1023 unselected controls) were studied by questionnaire, physical examination, echocardiographical assessment and biochemical analyses. The −174 G/C polymorphism was genotyped using a newly established PCR-RFLP. IL-6 levels were measured in a subset of 574 MI patients. Results: In the population-based sample, the IL-6 genotype was neither associated with traditional cardiovascular risk factors (systolic and diastolic blood pressure, total cholesterol, HDL and LDL cholesterol, body mass index, diabetes mellitus) nor with cardiac structural or functional parameters (left ventricular mass index, ejection fraction, diastolic inflow pattern). Moreover, the genotype distribution of the −174 G/C polymorphism was not different in MI patients (GG: 34.1%; GC: 47.4%; CC: 18.5%) and population-based controls (GG: 32.4%; GC: 48.8%; CC: 18.9%) ( p=0.67). IL-6 levels were neither related to the −174 G/C polymorphism ( p=0.29) nor to ACE-inhibitor treatment (2.16 with vs. 2.09 pg/ml without ACE-inhibitor, p=0.27). However, patients receiving statins displayed significantly lower IL-6 levels (1.83 vs. 2.32 pg/ml in the group without statins, p<0.0001). Conclusions: This extensive investigation failed to obtain evidence that the IL-6 −174 G/C promoter polymorphism affects traditional cardiovascular risk factors or the prevalence of myocardial infarction in a Caucasian sample.

No association of interleukin-6 gene polymorphism ($minus;174 G/C) with myocardial infarction or traditional cardiovascular risk factors*1

Background: Recently, a polymorphism at position −174 (G>C) of the interleukin-6 (IL-6) promoter was found to be associated with an increased prevalence of myocardial infarction (MI). The aim of the present study was to further investigate the association of the IL-6 −174 G/C allele status with specific end organ damage, i.e. myocardial infarction in large population-based samples. Methods: Individuals from two Bavarian samples of MI patients (total n=1322) and the population-based Augsburg MONICA survey (1023 unselected controls) were studied by questionnaire, physical examination, echocardiographical assessment and biochemical analyses. The −174 G/C polymorphism was genotyped using a newly established PCR-RFLP. IL-6 levels were measured in a subset of 574 MI patients. Results: In the population-based sample, the IL-6 genotype was neither associated with traditional cardiovascular risk factors (systolic and diastolic blood pressure, total cholesterol, HDL and LDL cholesterol, body mass index, diabetes mellitus) nor with cardiac structural or functional parameters (left ventricular mass index, ejection fraction, diastolic inflow pattern). Moreover, the genotype distribution of the −174 G/C polymorphism was not different in MI patients (GG: 34.1%; GC: 47.4%; CC: 18.5%) and population-based controls (GG: 32.4%; GC: 48.8%; CC: 18.9%) (p=0.67). IL-6 levels were neither related to the −174 G/C polymorphism (p=0.29) nor to ACE-inhibitor treatment (2.16 with vs. 2.09 pg/ml without ACE-inhibitor, p=0.27). However, patients receiving statins displayed significantly lower IL-6 levels (1.83 vs. 2.32 pg/ml in the group without statins, p<0.0001). Conclusions: This extensive investigation failed to obtain evidence that the IL-6 −174 G/C promoter polymorphism affects traditional cardiovascular risk factors or the prevalence of myocardial infarction in a Caucasian sample.

Interleukin-6 promoter polymorphism is associated with bone quality assessed by calcaneus ultrasound and previous fractures in a cohort of 75-year-old women

Interleukin 6 (IL-6) is a multifunctional cytokine and a potent stimulator of bone resorption and has been implicated in the pathogenesis of osteoporosis in postmenopausal women. The aim of this study was to investigate if a functional IL-6 promoter polymorphism (-174) was related to bone mass and fractures in a cohort consisting of 964 postmenopausal Caucasian women aged 75 years. Bone mineral density (BMD; g/cm2) of the femoral neck, lumbar spine and total body was measured using dual energy X-ray absorptiometry (DXA). Quantitative ultrasound (QUS) was also measured in the calcaneus and quantified as speed of sound (SOS; m/s), broadband ultrasound attenuation (BUA; dB/MHz), and stiffness index (SI). IL-6 genotypes was determined by restriction fragment length polymorphism (RFLP) using the restriction enzyme NlaIII. The frequencies of the different IL-6 genotypes were 27.5% (GG), 47.9% (GC), 24.6% (CC). The IL-6 polymorphism (presence of G) was independently related to a lower stiffness (beta=-0.07; P=0.03) and BUA (beta=-0.08; P=0.02), but not to BMD at any site measured by DXA. In the cohort, 420 subjects (44%) reported at least one fracture during their lifetime, and 349 (36%) reported at least one fracture after the age of 50. Using binary logistic regression, the IL-6 polymorphism (presence of G) was significantly related to an increased risk of a previous fracture during life (odds ratio 1.46, 95% CI 1.08-1.97) and to an increased risk of a fracture occurring after 50 years of age (odds ratio 1.37, 95% CI 1.004-1.88). The risk was further increased for fractures grouped as osteoporotic fractures (odds ratio 1.67, 95% CI 1.14-2.45), including forearm fractures (odds ratio 1.59, 95% CI 1.05-2.40). In conclusion, presence of G allele in the IL-6 promoter polymorphism at position -174 is independently related to previous fractures in postmenopausal women. This association may be related primarily to an altered bone quality identified by QUS and not a lower bone mass. This is also the first demonstration of association of IL-6 gene polymorphism to calcaneal QUS.