Biological variations, genetic polymorphisms and familial resemblance of TNF-α and IL-6 concentrations: STANISLAS cohort

Abstract

Cytokines are involved in the development of several inflammatory diseases and atherosclerosis. Their variations in healthy individuals are not well defined. The aims of this study were: firstly, to identify factors affecting biological variation of interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-a); secondly, to study their family resemblance; and thirdly, to evaluate the effect of two TNF-a (À308G/A and À238G/A) and two IL-6 polymorphisms (174G/C and À572G/C) on their corresponding circulating levels. A total of 171 healthy families selected from the STANISLAS cohort were studied. Age was negatively related to TNFa concentrations in offspring only (both sons and daughters). Additionally, IL-6 and TNF-a levels were differently influenced by gender, white blood cells, tobacco consumption, and HDL-cholesterol level. A weak significant familial resemblance for TNF-a concentration was observed in siblings only. There was no significant familial resemblance for IL-6 levels. The TNF-a À308A allele was associated with decreased TNFa concentrations in both offspring aged less than 18 and males without overweight (BMIo25 kg/m 2 ). Fathers carrying the IL-6 À174CC genotype had higher IL-6 levels than those with the IL-6 À174G allele. Parents with the IL-6 À572GG genotype had higher IL-6 concentrations than the C allele carriers. In this sample of healthy families, plasma levels of IL-6 and TNF-a were differently affected by biological parameters including age, gender and smoking, and the impact of their respective polymorphisms was influenced by gender, age and BMI.

Genetic polymorphisms in the cytokine genes and risk of hepatocellular carcinoma in low-risk non-Asians of USA

“…We are the first to be able to assess the association between IL-6 genetic polymorphism and HCC risk. Previous study found that the C allele of the IL-6 genotype is associated with increased protein levels (29). Our study demonstrated that among all the cytokine polymorphisms studied, the lowactivity IL-6 genotype showed the strongest effect on HCC risk.…”

Association between TNF-α −308G>A polymorphism and the development of acute coronary syndromes in Greek subjects: The CARDIO2000-GENE Study

“…[32][33][34][35] The stage of disease, the geographical origin, the age, as well as sex and the number of participants, are dynamics to read between the lines in order to explain the contrasting findings. The effect of these biological factors on TNF-␣ levels was extensively evaluated very recently 36 underlying the differentially result of each one in a total of 171 healthy families selected from the STANISLAS cohort.…”

Clinical Significance of Interleukin-6 (Il-6) Gene Polymorphism and Il-6 Serum Level in Pancreatic Adenocarcinoma and Chronic Pancreatitis

“…Polymorphic variants in the promoter region of the Il-6 gene may be responsible for variations in transcription that subsequently affect serum level of this cytokine [4,14]. The best characterized of these polymorphisms is a singlenucleotide polymorphism at position -174, upstream of the transcription start site, involving substitution of cytosine (C) for guanine (G).…”