Interaction of the glutathione S-transferase genes and cigarette smoking on risk of lower extremity arterial disease: the Atherosclerosis Risk in Communities (ARIC) study

Glutathione S-transferases Ml or T1 (GSTM1/GSTT1) affect the body's ability either to detoxify or to activate chemicals in cigarette smoke. Cigarette smoking increases the risk of lower extremity arterial disease (LEAD). We c onducted a cross-sectional study to evaluate a hypothesized interaction of the genetic polymorphisms of GSTM1 and T1 with cigarette smoking in the ris k of LEAD in the ARIC study. A stratified-random sample, including 212 LEAD cases (ankle-brachial index < 0.9 in men or < 0.85 in women) and 1277 non- cases, was selected From the ARIC cohort of 12 041 middle-aged participants free of CHD, transient ischemic attack and stroke at baseline (1987-1989). Overall, the differences in the Frequencies of GSTM1-0 and GSTT1-0 (the ho mozygous deletion genotype) were not statistically significant between case s and non-cases (44 vs. 41% and 28 vs. 18%). However. smoking was more prev alent among LEAD cases than non-cases. The results suggest that the non-del etion genotype GSTM1-1 interacts with smoking to increase the risk of LEAD, but this interaction was not statistically significant. The functional gen otype GSTT1-1 was significantly associated with increased risk of LEAD give n smoking after adjustment for other risk factors. In individuals with GSTT 1-1, the odds ratios (ORs) (95% confidence intervals) of LEAD were 3.6 (1.4 , 9.0) for current smoking and 5.0 (1.9, 13.0) for 20 + pack-years. However , in those with GSTT1-0, the ORs were 0.8 (0.2, 2.8) for current smoking an d 0.6 (0.1,2.1) for 20 + pack-years. The interaction was significant (P < 0 .05) on the additive scale for current smoking and on both the additive and multiplicative scales for 20 + pack-years. Among non-smokers, GSTT1-1 was not associated with LEAD. The results suggest that the GSTT1-1 polymorphism may be a susceptibility factor modifying the risk of LEAD associated with cigarette smoking. (C) 2001 Elsevier Science Ireland Ltd. All rights reserv ed.