Impact of ethnicity and MTHFR genotype on age at onset of coronary artery disease in women in Israel

Background: The C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is associated with early onset of coronary artery disease in some populations with certain ethnic backgrounds. However, data on its effect on CAD development in women are limited and conflicting. Objectives: To investigate the effects of the MTHFR C677T mutation and ethnicity on the development and age at onset of CAD in women in Israel. Methods: The sample included 135 Jewish women with well-documented CAD (62 Ashkenazi, 44 Oriental and 29 of other origins) in whom CAD symptoms first developed at age ≤ 65 years. DNA samples from 235 women served as the control. Results: CAD symptoms developed later in Ashkenazi than in Oriental women or women of other origins (51.0 ± 7.0 years vs. 48.3 ± 7.5 and 46.3 ± 7.7 years, respectively, P = 0.024). Among Ashkenazi women, the T/T genotype was less common in patients in whom CAD symptoms appeared after age 50 (6.4%) than in patients with earlier CAD symptoms (25.8%, P = 0.037) and Ashkenazi control subjects (23.3%, P = 0.045). Among women from other origins, these differences were not significant. On logistic regression analysis, the T/T genotype was associated with a nearly fourfold increase in the risk of early onset (age < 45 years) of CAD (odds ratio 3.87, 95% confidence interval 1.12-13.45, adjusted for risk factors and origin) and a trend towards an influence of ethnicity (P = 0.08). Compared to Ashkenazi women, the risk of early development of CAD associated with the T/T genotype among Oriental ones was 0.46 (95%CI 0.189-1.114) and in women of other origins, 5.84 (95%CI 1.76-19.34). Each additional risk factor increased the risk of earlier onset of CAD by 42% (OR 1.42, 95%CI 1.06-1.89). Conclusions: The age at onset of CAD in Israeli women is influenced by the MTHFR genotype, ethnic origin and coronary risk factors.