Long-term survival after ischemic stroke in postmenopausal women is affected by an interaction between smoking and genetic variation in nitric oxide synthases

N. K. J Oksala, A Oksala, Timo Erkinjuntti, Tarja Pohjasvaara, T Kunnas, R Vataja, Markku Kaste, P. J Karhunen

Research output: Contribution to journalArticleScientificpeer-review


"Background: We aimed to study whether variations in vaso-regulatory endothelial nitric oxide synthase (eNOS 4a/b) and tissue-injury-associated inducible nitric oxide synthase (iNOS R5/4) genes and smoking might explain gender differences in long-term survival after stroke. Methods: A total of 486 consecutive acute stroke patients, subjected to MRI, were followed up for a mean of 7.6 years. The eNOS 4a/b (n = 300) and iNOS R5/4 (n = 310) genotypes were determined by PCR. Of these patients, 213/300 (71.0%; eNOS 4a/b) and 223/310 (71.9%; iNOS R5/4) had died. Results: Despite the fact that women were older than men (72.3 vs. 69.5 years, p = 0.001) at recruitment, poor long-term survival was not sex-related, but instead predicted by age (p < 0.0001), cardiac failure (p = 0.004), smoking (p = 0.017), diabetes (p = 0.049), and variation in the eNOS gene locus (p = 0.033). Smoking and variations in both eNOS [hazard ratio (HR) = 1.53, p = 0.011] and iNOS loci (HR = 1.52, p = 0.073) were found to impact upon poor survival. We found a strong interaction between smoking, female sex, and the iNOS R5/4 genotype with the risk of death (HR = 3.23, CI = 1.51-6.90, p = 0.002). Compared with nonsmoking noncarriers, postmenopausal women who had been smokers and carried either the rare iNOS R5 allele (17.1%; HR = 4.23, CI = 1.84-9.75, p = 0.001) or the common eNOS 4b allele (71%; HR = 3.14, CI = 1.49-6.62, p = 0.003) were at a higher risk of death during the follow-up. These interactions were independent of each other, and were not found among men. Conclusions: The interaction between smoking and genetic variants of eNOS and iNOS predicts survival after stroke, especially among postmenopausal women. Copyright (C) 2008 S. Karger AG, Basel."
Original languageEnglish
JournalCerebrovascular Diseases
Issue number3
Pages (from-to)250-258
Number of pages9
Publication statusPublished - 2008
MoE publication typeA1 Journal article-refereed

Fields of Science

  • 312 Clinical medicine

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