Briggs FB, Acuna B, Shen L, Ramsay P, Quach H, Bernstein A, Bellesis KH, Kockum IS, Hedström AK, Alfredsson L, Olsson T, Schaefer C, Barcellos LF. Smoking and Risk of Multiple Sclerosis: Evidence of Modification by NAT1 Variants. Epidemiology. 2014 Mar. [Epub ahead of print]
BACKGROUND:: Tobacco smoke is an established risk factor for multiple sclerosis (MS). We hypothesized that variation in genes involved in metabolism of tobacco smoke constituents may modify MS risk in smokers.
METHODS:: A three-stage gene-environment investigation was conducted for NAT1, NAT2, and GSTP1 variants. The discovery analysis was conducted among 1588 white MS cases and controls from the Kaiser Permanente Northern California Region HealthPlan (Kaiser). The replication analysis was carried out in 988 white MS cases and controls from Sweden.
RESULTS: Tobacco smoke exposure at the age of 20 years was associated with greater MS risk in both data sets (in Kaiser, odds ratio [OR] = 1.51 [95% confidence interval (CI) = 1.17-1.93]; in Sweden, OR = 1.35 [1.04-1.74]). A total of 42 NAT1 variants showed evidence for interaction with tobacco smoke exposure (Pcorrected < 0.05). Genotypes for 41 NAT1 single nucleotide polymorphisms (SNPs) were studied in the replication data set. A variant (rs7388368C>A) within a dense transcription factor-binding region showed evidence for interaction (Kaiser, OR for interaction = 1.75 [95% CI = 1.19-2.56]; Sweden, OR = 1.62 [1.05-2.49]). Tobacco smoke exposure was associated with MS risk among rs7388368A carriers only; homozygote individuals had the highest risk (A/A, OR = 5.17 [95% CI = 2.17-12.33]).
CONCLUSIONS: We conducted a three-stage analysis using two population-based case-control datasets that consisted of a discovery population, a replication population, and a pooled analysis. NAT1 emerged as a genetic effect modifier of tobacco smoke exposure in MS susceptibility.
We have been banging on that smoking is a risk factor for MS,this study further supports this view using Californian and Swedish data. However in this study they link this risk factor to thepresence of certain genes. N-acetyltransferase 1 is an isoenzymes responsible for the metabolism of numerous drugs and carcinogens. In this study if yu had a variant of this protein it increases your risk of developing MS over five fold. This is a nice example of where your genetics can inter act with an environmental factor (e.g. peer pressure to smoke) to increase your risk f developing MS
Labels: MS risk