The influence of IL-6 polymorphism on efficacy of treatment of rheumatoid arthritis patients with methotrexate and prednisone

Rheumatoid arthritis (RA) is a chronic inflammatory disease in which cytokines play an important role. The therapy of RA is associated with application of the drugs modulating the immune response via inhibiting the cytokine production. The common drugs used in RA therapy are methotrexate and prednisone. Recent investigations showed the importance of genetically determined differences in cytokine production in RA activity and therapy. The aim of the present study was to examine the influence of - 174 interleukin-6 (IL-6) promoter polymorphism on the efficacy of treatment of RA patients with methotrexate and prednisone. Polymerase chain reaction amplification was used for analysis of the polymorphism at IL-6 gene. Seventy patients with RA diagnosed according to the criteria of the American College of Rheumatology were investigated. The patients were divided into two subgroups. The first subgroup included patients who have obtained remission for at least 6 months after therapy with methotrexate and glucocorticosteroids. The second subgroup included patients with active disease despite at least 6 months of therapy with methotrexate and glucocorticosteroids. It has been shown that the incidence of remission after therapy with methotrexate and glucocorticosteroids was significantly lower in patients with GG genotype as compared with GC and CC genotypes p< 0.05. We suggest that -174 IL-6 promoter polymorphism may be a genetic risk factor determining the effectiveness of RA treatement with methotrexate and glucocorticosteroids.     

Lack of association between IL-6 gene polymorphisms and rheumatoid arthritis in Turkish population

Inflammatory cytokines play an important role in the pathogenesis of rheumatoid arthritis (RA). One of candidate genes is interleukin-6 (IL-6), and single-nucleotide polymorphisms in the promoter region of IL-6 were found to be associated with RA. The aim of this study was to determine the association between IL-6 promoter polymorphisms (-174, -572, -597) and RA in Turkish population. A total of 425 subjects were recruited into the study (247 healthy controls and 178 RA). The promoter region of IL-6 gene was amplified by PCR using DNAs from patients and the controls, and their PCR products were digested by suitable enzymes. No significant association was found between RA and -174 genotype distribution (P = 0.535) and allele frequency (P = 0.230). There was also no relationship between -572 (P = 0.150) and -597 (P = 0.912) gene polymorphism and RA. Our results suggested that IL-6 gene promoter polymorphisms have no association with RA in Turkish population.     

Clinical significance of serum interleukin-6 and −174 G/C promoter polymorphism in Rheumatoid arthritis patients

Aim of the workTo evaluate the clinical significance of serum levels of interleukin-6 (IL-6) and ?174 G/C promoter polymorphism in Rheumatoid arthritis (RA) patients.Patients and methodsWe studied 37 RA patients and 10 age and gender matched healthy controls. Demographic, clinical and serological data were prospectively evaluated. Disease activity score (DAS28) and Health Assessment Questionnaire (HAQ) were assessed. Serum IL-6 level was measured and promoter (?174G/C) genotyped.ResultsSerum IL-6 levels were significantly higher in RA patients compared to control (p = 0.04), especially those with CC promoter polymorphism. Twenty-four patients had GG IL-6 (?174 G/C) gene promoter polymorphism, 11 were GC and 2 CC. Nine controls were GG and 1 GC. In patients with more advanced polymorphism (?174 CC) there was a significantly increased functional impairment (HAQ score) (p = 0.029) and platelet count (p = 0.049). In those with GG genotype, there was a significant correlation between IL-6 and Morning stiffness duration (r = 0.44,p = 0.03), while those with GC genotype had a significant negative correlation of the IL-6 level with the parameters of disease activity and the DAS28 (r = ?0.69,p = 0.019). None of the studied parameters would predict the IL-6 promoter polymorphism.ConclusionSerum IL-6 levels and ?174 G/C promoter polymorphism were higher in RA patients than in healthy controls. The inverse relation of IL-6 with the DAS28 in those with an increased IL-6 promoter polymorphism may confirm its increased involvement in the pathogenesis of RA and in the increased disease activity which may point to the need for considering of anti-IL-6 agents in their management plan.     

The −590 IL-4 promoter polymorphism in patients with rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory disease in which cytokines play an important role. The aim of the present study was to evaluate the –590 IL-4 promoter polymorphism in patients with RA and its association with disease activity and severity. We enrolled 94 patients with RA diagnosed according to the criteria of the American College of Rheumatology. Polymerase chain reaction amplification was used for analysis of the polymorphism at position –590 of the promoter of the IL-4 gene. The distribution of IL-4 genotypes in RA patients did not differ from control subjects. Nevertheless, the active form of RA was more frequently diagnosed in patients with T allele (genotypes CT and TT) as compared with homozygous CC patients. Moreover, in carriers of the T allele, parameters of disease activity (DAS 28 score, ESR, number of swollen and tender joints) were significantly increased. We suggest that the IL-4 –590 promoter polymorphism may be a genetic risk factor for RA severity.     

Interleukin-10 promoter polymorphism in patients with rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory disease in which interleukin (IL)-10 plays an important role. There are, however, controversial reports that IL-10 promoter polymorphism may be an independent marker of susceptibility and severity of RA. The aim of the present study was to examine the IL-10 promoter polymorphism in patients with RA. We examined 95 patients with rheumatoid arthritis diagnosed according to the criteria of the American College of Rheumatology. Polymerase chain reaction amplification was used for analysis of the promoter polymorphism of the IL-10 gene. In RA patients, the prevalence of genotypes encoding high expression of IL-10 was observed. Nevertheless, there was no association between IL-10 genotypes and age at disease diagnosis, disease activity in a physicians global assessment, and joint and extra-articular involvement. There was also no correlation between IL-10 polymorphism and disease activity parameters—erythrocyte sedimentation rate, C-reactive protein, number of swollen and tender joints, and duration of morning stiffness. We suggest that IL-10 promoter polymorphism is not a genetic risk factor for RA activity.     

IL1beta+3953 exon 5 and IL-2 -330 promoter polymorphisms in patients with rheumatoid arthritis

OBJECTIVE: Rheumatoid arthritis (RA) is chronic inflammatory disease in which cytokines play an important role. The aim of present study was to evaluate the exon 5 +3953 IL-1beta and IL-2 -330 promoter polymorphisms in patients with RA in association with disease activity and severity. METHODS: In the study 93 patients with rheumatoid arthritis diagnosed according to the criteria of American College of Rheumatology were included. Polymerase chain reaction amplification was used for analysis of the polymorphisms studied. RESULTS: The distribution of IL-1beta and IL-2 genotypes in RA patients did not differ from control subjects. Nevertheless in patients with A2 allele of IL-1beta and GG genotype of IL-2, the active form of RA was more frequently diagnosed. Moreover in these patients the measurements of disease activity (DAS 28 score, ESR, number of swollen and tender joints) were significantly increased. CONCLUSION: We suggest that exon 5 +3953 IL1beta and IL-2 -330 promoter polymorphisms may be a genetic risk factor for RA severity.     

TNF-alpha -308 promoter polymorphism in patients with rheumatoid arthritis

OBJECTIVES: Rheumatoid arthritis (RA) is a chronic inflammatory disease in which tumour necrosis factor-alpha (TNF-alpha) plays an important role. There are, however, controversial reports that TNF-alpha promoter polymorphism may be an independent marker of susceptibility and severity of RA. The aim of the present study was to examine the TNF-alpha -308 promoter polymorphism in patients with RA. METHODS: We examined 91 patients with RA diagnosed according to the criteria of the American College of Rheumatology. Polymerase chain reaction (PCR) amplification was used for analysis of the polymorphism at position -308 in promoter of TNF-alpha gene. RESULTS: Distribution of TNF-alpha genotypes in RA patients did not differ from that in control subjects. Moreover, there was no association between TNF-alpha genotypes and age at disease diagnosis, disease activity in global physician's assessment, and joint and extra-articular involvement. There was also no correlation between TNF-alpha polymorphism and disease activity measures, including erythrocyte sedimentation rate (ESR), CRP, number of swollen and tender joints, and morning stiffness duration. CONCLUSIONS: We suggest that TNF-alpha -308 promoter polymorphism is not a genetic risk factor for RA susceptibility and severity.     

Interleukin 6-174 G/C promoter gene polymorphism and sporadic Alzheimer's disease: geographic allele and genotype variations in Europe

The interleukin 6 (IL-6) gene in humans is located in the short arm of chromosome 7 and has a-174 G/C polymorphism in its promoter region. The C allele at position-174 in the promoter of the interleukin 6 (IL-6) gene has been associated with reduced gene expression and reduced plasma levels of IL-6. Given the supposed role of several inflammatory mediators in neurodegeneration and Alzheimer's disease (AD), the IL-6-174 G/C promoter polymorphism has been associated with AD with contrasting findings. First aim of the present study was to investigate whether there was evidence in Southern Italy of an association between the IL-6-174 G/C promoter polymorphism and AD. Secondly, we also tested a possible effect of geographic genetic variations on existing reported associations comparing our results with the findings from published studies on other European populations. We examined apolipoprotein E (APOE) and IL-6-174 G/C promoter polymorphisms in a cohort of 168 sporadic AD patients and 220 sex- and age-matched nondemented controls from Southern Italy. No differences have been found in the IL-6-174 G/C promoter allele and genotype frequencies between AD patients and controls nor in early- and late-onset subsets of AD patients. No statistically significant differences in frequencies between IL-6-174 G/C promoter alleles and AD among APOE allele strata were found. Finally, comparing our results with the findings from other European populations, the IL-6*G/*G genotype frequency showed a statistically significant increasing trend from Northern to Southern regions of Europe in AD patients and controls, with a concomitant increase in IL-6*C/*G genotype frequency. Furthermore, an increasing geographical trend from North to South was found for the IL-6*G allele, with a concomitant inverse trend for IL-6*C allele. We suggest that regional European differences in genotype and allele frequencies of the IL-6-174 G/C promoter polymorphism may explain in part controversial findings on this polymorphism in AD in various European studies.     

The endothelial dysfunction in patients with type 2 diabetes mellitus is associated with IL-6 gene promoter polymorphism in Chinese population

The purpose of this study is to examine the effects of IL-6 gene promoter -174G/C and -572G/C polymorphism on endothelial function of Chinese T2DM and normal glucose regulation (NGR) subjects. 512 newly diagnosed T2DM patients and 483 NGR subjects were recruited and Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) was performed for the IL-6 gene promoter -174G/C and -572G/C polymorphism. Flow-mediated dilation (FMD) was measured as a non-invasive indicator for endothelial function. The results show that the C allele and CC genotype at -174 of IL-6 gene promoter region was extremely rare in both T2DM and NGR groups; genotypes' and alleles' frequency at -572 of IL-6 gene promoter region is of no difference between T2DM and NGR groups; within T2DM group, higher plasma IL-6 concentration and lower FMD was found in patients with -572 GC (2.36 ± 0.69, 4.23 ± 3.82%) or GG (2.32 ± 0.74, 4.24 ± 3.67%) genotype, compared with patients with CC (2.15 ± 0.62, 5.28 ± 3.94%) genotype. The conclusion of the study is that in comparison with patients of CC genotype, the T2DM patients of -572 GC or GG genotype may have more aggravated endothelial dysfunction (ED) and be at higher risk for coronary artery disease (CAD).     

Relationship between interleukin 6 promoter polymorphism at position -174, IL-6 serum levels, and the risk of relapse/recurrence in polymyalgia rheumatica

OBJECTIVE: To assess the role of -174 G/C promoter polymorphism of interleukin 6 (IL-6) in the susceptibility to polymyalgia rheumatica (PMR). We also investigated whether this polymorphism modulates the circulating level of IL-6 and the risk of relapse/recurrence in a series of patients with PMR followed up prospectively. METHODS: A prospective study of 112 consecutive, untreated patients with isolated PMR (i.e., without evidence of giant cell arteritis) who were followed up for at least 24 months. This cohort represented all patients diagnosed over a 5-year period in one Italian rheumatological secondary referral center. Patients were monitored for clinical signs/symptoms and acute-phase reactants. All PMR patients and 112 population-based controls from the same geographic area were genotyped for IL-6 polymorphism at position -174 by molecular methods. IL-6 serum levels were measured in 67 PMR patients and 43 population-based controls. RESULTS: The distribution of the G/C 174 genotype was similar in PMR patients and controls. No significant associations with IL-6 promoter polymorphism at position -174 were found when PMR patients with and without relapse/recurrence were compared. Controls homozygous for the C allele had higher serum IL-6 levels than the carriers of the G allele (4.5 +/- 3.7 pg/ml vs 1.8 +/- 2.1 pg/ml, p = 0.01). Patients homozygous for the allele C had significantly higher values of IL-6 during followup than patients carrying GC or GG genotypes. CC homozygosity was significantly more frequent in patients with persistently elevated levels of IL-6 than in those without. The presence of persistently elevated IL-6 levels, but not the CC genotype, was associated with an increased frequency of relapse/recurrence. CONCLUSION: Our findings show that the 174 G/C promoter IL-6 polymorphism is not implicated in susceptibility to PMR. However, CC genotype characterized PMR patients with persistently elevated levels of IL-6 who are at higher risk of developing relapse/recurrence. A genetically modulated pattern of IL-6 production could affect the longterm outcome of patients with PMR.     

Interleukin 6 gene promoter polymorphism is not associated with ankylosing spondylitis

OBJECTIVE: To investigate the possible association between the recently described interleukin 6 (IL-6) promoter polymorphisms at position -174, and susceptibility to ankylosing spondylitis (AS). METHODS: Ninety-two patients with AS, 157 healthy controls, and an additional group of 52 HLA-B27 positive unrelated individuals were included in this study. The -174 polymorphic site in the promoter region of IL-6 gene was typed by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: No statistically significant differences were observed when IL-6 promoter genotype and allele distribution between patients with AS and healthy controls were compared. CONCLUSION: Our results suggest the -174 IL-6 polymorphism does not play an important role in susceptibility to AS. Larger studies are needed to provide more conclusive evidence on the role of -174 IL-6 polymorphism in AS.     

Interleukin-6 promoter polymorphism (--174 G/C) in Caucasian German patients with systemic lupus erythematosus

BACKGROUND: A biallelic polymorphism (--174 G/C) within the interleukin-6 (IL-6) promoter reportedly has functional importance through the modulation of IL-6 expression in vitro and in vivo. METHODS: We performed a population-based case-control study to analyse the association of the --174 G/C polymorphism with disease susceptibility and clinical manifestations in 211 German patients with systemic lupus erythematosus (SLE). RESULTS: There were no significant differences in allelic and genotypic frequencies between patients and healthy controls. Comparing patients with various disease manifestations, we found an association of the --174 G allele with discoid skin lesions (Pc=0.034) and anti-histone antibodies (Pc=0.009). CONCLUSIONS: The IL-6 promoter polymorphism --174 G/C does not contribute significantly to disease susceptibility, but predisposes to distinct clinical and immunological features. A genetically determined high IL-6 response may have a pathogenic role under these conditions.     

IL-6启动子多态性与阿尔茨海默氏病的相关性探讨

目的 探讨细胞因子白介素6(IL—6)与阿尔茨海默氏病(AD)的相关性。方法 用PCR—RFLP技术检测356例英国AD患者和434例对照者IL-6启动子-174C／G多态性，并进行了对比分析。结果 IL-6启动子-174C／G多态性与AD无相关性。其与AD发病年龄、β淀粉样蛋白沉积量和小神经胶质细胞含量无明显相关性。结论 IL-6启动子-174C／G多态性不是AD的危险因素。     

Association of low-grade inflammation with nephropathy in type 2 diabetic patients: role of elevated CRP-levels and 2 different gene-polymorphisms of proinflammatory cytokines.

BACKGROUND: Chronic inflammatory processes are thought to play a key role in the development of micro- and macrovascular complications in type 2 diabetes mellitus. An association between low -grade inflammation and type 2 diabetes has been described in some studies. We assayed the association of two frequent polymorphisms in proinflammatory cytokines: the interleukin 6 G(-174)C promoter polymorphism [IL-6G(-174)C], the exon 2 interleukin receptor antagonist insertion deletion polymorphism [IL1RA]) and serum CRP levels with the prevalence of diabetic nephropathy in patients suffering from type 2 diabetes mellitus. SUBJECTS AND METHODS: A total of 141 patients with type 2 diabetes mellitus, with and without diabetic nephropathy was genotyped for the above mentioned polymorphisms: 66 with normoalbuminuria, 31 with microalbuminuria and 44 with macroalbuminuria. CRP levels were analysed by a high sensitivity - immunnephelometric assay. RESULTS: While a significant association be-tween macroalbuminuria and CRP could be observed (p<0,015), no associations were found between IL-6G(-174)C or IL1RA genotype and any stage of nephropathy. CRP-levels were similar in the 3 different IL-6G(-174)C genotypes as well as in the 2 IL1RA genotypes. CONCLUSIONS: In type 2 diabetic subjects elevated CRP levels are associated with an increased prevalence of albuminuria. The two investigated proinflammatory polymorphisms do not seem to contribute to initiation of nephropathy in type 2 diabetic patients but we cannot exclude effects of these polymorphisms on course of nephropathy.     

Genetic association of cytokines polymorphisms with autoimmune hepatitis and primary biliary cirrhosis in the Chinese

AIM: To characterize gene polymorphism of several cytokine gene in-patients with AIH and PBC and to analyze the difference of the polymorphism distribution between Chinese patients and healthy controls. METHODS: The study population consisted of 62 patients with AIH, and 77 patients with PBC. The genetic profile of four cytokines was analyzed by restriction fragment length polymorphism after specific PCR amplification (PCR-RFLP) or sequence-specific primers PCR (SSP-PCR). The analyzed gene polymorphism included interleukin-1 (IL-1) (at position +3 953 and IL-1RN intron 2), IL-6 (at position -174), IL-10 promoter (at position -1082, -819, and -592). The control group consisted of 160 healthy blood donors. RESULTS: The majority of Chinese people including patients and healthy controls exhibited IL-1B 1,1 genotype, and there was no significant difference in AIH, PBC patients and controls. There were highly statistically significant differences in the distribution of the IL-1RN gene polymorphism between the patients with PBC compared with controls. The frequency of IL-1RN 1,1 was significantly higher (90.9% vs 79.4%, P=0.03) and the frequency of IL-1RN 1,2 was significantly lower in PBC patients (6.5% vs 17.5%, P=0.01). No statistical difference was observed between AIH patients and controls. All of the 160 healthy controls and 62 cases of AIH patients exhibited IL-6-174GG genotype, and there were four cases, which expressed IL-6-174GC genotype in 77 cases of PBC patients. The frequency of IL-6-174GC was markedly significantly higher in PBC patients compared with controls (5.2% vs 0%, P=0.004). No statistically significant difference was found in the distribution of IL-10 promoter genotype in AIH and PBC patients compared with controls. CONCLUSION: The polymorphisms of IL-1RN and IL-6-174G/C appear to be associated with PBC in Chinese patients.     

Interleukin-6 promoter polymorphism −174 G/C is associated with nephritis in Portuguese Caucasian systemic lupus erythematosus patients

Interleukin-6 (IL-6) is a multifunctional cytokine with an important pathophysiological role in systemic lupus erythematosus (SLE). The polymorphism of the IL-6 gene promoter at position −174, which appears to influence the production of this cytokine, has been associated with susceptibility to some rheumatic diseases. The aim of this study is to investigate whether the IL-6 −174 G/C polymorphism associates with lupus susceptibility or affects disease characteristics in Portuguese patients with SLE. The association between −174 G/C and lupus diagnosis was studied in 115 adult SLE patients (95.7% females) and 152 healthy controls (94.7% females), all Caucasians. There were no significant differences in genotype or allele frequency between patients and controls. The −174 C/C genotype was independently associated with renal disease and the C allele with the presence of irreversible damage. The IL-6 gene promoter polymorphism at position −174 does not contribute to SLE susceptibility in Portuguese Caucasian patients but may predispose to specific manifestations of the disease.     

Lack of association between IL6 single nucleotide polymorphisms and cardiovascular disease in Spanish patients with rheumatoid arthritis

Introduction

Rheumatoid arthritis (RA) is a complex polygenic inflammatory disease associated with accelerated atherosclerosis. IL-6 is a key mediator of inflammation in RA. A recent study showed an association between IL6-174 G/C gene polymorphism and cardiovascular (CV) disease in UK individuals with RA. To confirm this association we assessed the influence of three IL6 gene polymorphisms in the risk of CV disease in a large series of patients with RA.

Material and methods

We studied 1250 Spanish patients with RA. Besides genotyping the traditional single nucleotide polymorphism (SNP) promoter -174G/C (rs1800795), we assessed another two SNPs (rs2069827 and rs2069840) located in the IL6 gene that were selected by SNP-tagging.

Results

Two-hundred and twenty (17.6%) of the 1250 patients experienced CV events. No significant differences in the genotype, allele and haplotype frequencies between RA patients with and without CV events were observed.

Conclusion

Our results do not confirm in a Spanish population the association of IL6 gene with CV disease in RA previously reported in the UK.     

Interleukin-6 promoter polymorphism at position -174 in giant cell arteritis

OBJECTIVE: To investigate potential associations between the -174 G/C interleukin-6 (IL-6) promoter polymorphism and susceptibility to and clinical features of giant cell arteritis (GCA), particularly in patients with or without polymyalgia rheumatica (PMR) and with or without ischemic complications. METHODS: One hundred and twenty-six patients with biopsy-proven GCA who were residents in Reggio Emilia, Italy, and 112 population-based controls from the same geographic area were genotyped for IL-6 polymorphism at position -174 by molecular methods. Patients were divided in subgroups according to presence or absence of PMR and ischemic complications (visual loss, jaw claudication, cerebrovascular accidents, aortic arch syndrome). RESULTS: Distribution of the G/C 174 genotype was similar in patients with GCA and controls. No significant associations with the IL-6 promoter polymorphism at position -174 were found when GCA patients with or without PMR or with or without ischemic complications were compared. Further, IL-6 genotypes did not significantly affect levels of C-reactive protein or other inflammatory markers at diagnosis. CONCLUSION: Our findings show that the 174 G/C promoter IL-6 polymorphism does not seem to be implicated in susceptibility to and clinical expression of GCA.     

Association between inflammatory markers and the interleukin-6 -174 G/C polymorphism is abolished in peripheral arterial occlusive disease.

AIM: The interleukin-6 (IL-6) -174 G/C polymorphism has been reported to determine IL-6 levels and contribute to the development of cardiovascular disorders. The aim of our study was to evaluate the effect of the IL-6 -174 G/C polymorphism on hemostatic or inflammatory markers in patients with peripheral arterial occlusive disease (PAOD), a common manifestation of obliterative atherosclerosis. METHODS: Plasma IL-6, fibrinogen, C-reactive protein (CRP), tissue plasminogen activator, plasminogen activator inhibitor-1 (PAI-1), fibrinopeptide A and intercellular adhesion molecule-1 levels were determined in PAOD patients (n=50) and healthy controls (n=30) genotyped for the IL-6 -174 G/C polymorphism. RESULTS: In the control group, IL-6, CRP and fibrinogen levels were significantly associated with the IL-6 -174 G/C polymorphism with a gene-dosage effect being the highest in the CC subjects and the lowest in those with the GG genotype (P<0.0001, P=0.0002 and P=0.0001, respectively). Interestingly, the CC homozygotes had lower PAI-1 levels than carriers of the G allele (P=0.04). In PAOD patients, the IL-6 -174 G/C polymorphism had no effect on all the variables measured. CONCLUSION: In contrast to apparently healthy subjects, the IL-6 -174 G/C polymorphism showed no association with plasma IL-6, CRP, fibrinogen and PAI-1 levels in PAOD patients.     

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.