We investigated whether smoking would interact with the interleukin-6 (IL-6) polymorphisms (-174G > C and -572C > G, -597G > A and -1363G > T) in determining circulating levels of inflammatory markers and its consequence to oxidative stress. The G/G genotype (n = 26) of the -572C > G in nonsmokers (n = 376) was associated with higher IL-6 (P = 0.028), fibrinogen (P = 0.007) and ox-LDL (P = 0.006) than those with C/C (n = 209) or C/G (n = 141). Results were similar for nonsmokers and smokers (n = 268), but in smokers, the -572G/G genotype was associated with a greater difference in levels of IL-6 (P = 0.031), fibrinogen (P = 0.001), ox-LDL (P = 0.037) and PGF2α (P = 0.050). IL-6 had positive relations with CRP, fibrinogen, ox-LDL and PGF2α. There was no evidence of an effect of -572C > G genotype on CRP levels in nonsmokers, however, this polymorphism was associated with a highly significant effect on CRP in smokers (P < 0.001) (genotype-smoking interaction P = 0.04, adjusted for age, BMI and IL-6). The C allele frequency at the -174 promoter region of IL-6 was very rare (<0.01) and -597G > A and -1363G > T were monomorphic in this study. Our results suggest that IL-6 -572C > G has a greater response over time to the inflammatory effects of smoking and this may result in smokers having higher oxidative stress in subjects with G/G compared to C/C or C/G.
Bibliographical noteFunding Information:
Healthy male subjects (n = 644) were recruited concomitantly from participants in prospective human genetic study, supported by a Genome Research Development Project on Health and Medicine (Project No. A000385), Ministry of Health and Welfare. The inclusion criteria were 38 ⩽ age 3 cigarettes per day as ‘regular smokers’ (n = 268).
This study was partly supported by (1) Ministry of Science and Technology, Seoul, Korea (M10642120002-06N4212-00210); (2) National Research Laboratory Project No. R0A-2005-000-10144-0, Ministry of Science and Technology, Seoul, Korea; (3) Korea Health 21 R&D Projects, Ministry of Health and Welfare, Seoul, Korea (A000385, A050376).
All Science Journal Classification (ASJC) codes
- Immunology and Allergy
- Molecular Biology