We have studied the effect of common mutations (677C ! T and 1298A ! C) of the methylenetetrahydrofolate reductase (MTHFR) gene in sixty-six healthy French subjects, aged 27±47 years. Serum folate, vitamin B 12 , and plasma total homocysteine were measured as well as the speci®c activity of MTHFR in lymphocytes. The frequency of subjects homozygous for the 677TT genotype was 18 %, and that of those homozygous for the 1298CC genotype was 12×5 %. The frequency of individuals heterozygous for both mutations was 23×5 %. The 1298A ! C mutation was associated with decreased MTHFR speci®c activity in subjects with both 677CC and 677CT genotypes. This activity was 60 % for the 677CC/1298AC genotype and 52 % for the 677CC/ 1298CC genotype when compared with the MTHFR speci®c activity of the 677CC/1298AA genotype. Heterozygotes for both mutations (677CT/1298AC genotype) had 36 % of the reference speci®c activity. Although homocysteine levels in 677TT and 1298CC genotype subjects were higher than for other genotypes, no signi®cant differences were observed among different genotypes. This may be due to high serum folate level in our samples, and suggests that folate therapy may be useful to prevent hyperhomocysteinaemia in homozygous mutant subjects.

No 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.