Abstract
Glutathione S-transferases M1 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 conducted a cross-sectional
study to evaluate a hypothesized interaction of the genetic polymorphisms of GSTM1
and T1 with cigarette smoking in the risk 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 homozygous deletion
genotype) were not statistically significant between cases and non-cases (44 vs. 41%
and 28 vs. 18%). However, smoking was more prevalent among LEAD cases than non-cases.
The results suggest that the non-deletion genotype GSTM1-1 interacts with smoking
to increase the risk of LEAD, but this interaction was not statistically significant.
The functional genotype GSTT1-1 was significantly associated with increased risk of
LEAD given smoking after adjustment for other risk factors. In individuals with GSTT1-1,
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 and 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.
Keywords
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Article Info
Publication History
Accepted:
June 17,
2000
Received in revised form:
May 16,
2000
Received:
December 2,
1999
Identification
Copyright
© 2001 Elsevier Science Ireland Ltd. Published by Elsevier Inc. All rights reserved.
