Apolipoprotein E gene promoter (–219G/T) polymorphism is associated with premature coronary heart disease

Abstract

The relationship of two apolipoprotein (apo) E gene polymorphisms and coronary heart disease (CHD) was investigated in 118 Finnish families with premature CHD and in 110 healthy control subjects. Affected siblings and probands with premature CHD had higher frequencies of the T allele of the -219G/T promoter polymorphism and the epsilon 4 allele (genotypes epsilon 4/3 or epsilon 4/4) of the apo epsilon 2/epsilon 3/ epsilon 4 polymorphism than those of healthy control subjects. Additionally, when the two apo E gene polymorphisms were combined, affected siblings and probands had a higher frequency of the -219T allele and the epsilon 4 allele combinations than did healthy controls. The -219T and the epsilon 4 alleles both separately and together were associated with higher levels of 2-h glucose in an oral glucose tolerance test. These results indicate that the two polymorphisms of the apo E gene have similar effects on the risk of coronary atherosclerosis in families with premature CHD. This risk was not explained by the effect of apo E gene polymorphisms on cholesterol metabolism, but their effect on cardiovascular risk factor clustering with insulin resistance may be of importance. We conclude that in addition to the epsilon 4 allele, also the -219G/T promoter polymorphism of the apo E gene is associated with early onset CHD.

Relations of APOE promoter polymorphisms to LDL cholesterol and markers of subclinical atherosclerosis in young adults

“…The frequencies of the 2219G and 2219T alleles were 0.62 and 0.38, respectively, and those of the 1113G and 1113C alleles were 0.63 and 0.37. The promoter genotype distributions were in Hardy-Weinberg equilibrium and similar to those seen in previous Finnish studies (1,17,18). Age, BMI, systolic or diastolic blood pressure, and smoking did not differ significantly between the APOE promoter genotype groups in the e3/e3 carriers ( Tables 1, 2).…”

Associations of apolipoprotein E gene with ischemic stroke and intracranial atherosclerosis

“…12 Moreover, the À219G/T polymorphism has been reported to associate with atherogenic lipid and lipoprotein profile, 13,14 as well as with coronary atherosclerosis. 15 However, the role of these SNPs in IS and in cerebral atherosclerosis has not been studied before.…”

Impact of Genetic Polymorphisms on Insulin Resistance

“…Some studies have suggested that the APOE ε2/ε3/ε4 polymorphism may modify the effect of insulin on CHD or some CHD risk factors, including obesity and lipid profile levels (Després et al, 1993;Valdez et al, 1995;Elosua et al, 2003), whereas the Framingham Offspring Study and Turkish Adult Risk Factor (TARF) Study found that this polymorphism was not associated with insulin resistance (Meigs et al, 2000;Komurcu-Bayrak et al, 2011). Two other of the functional SNPs, i.e., -219G>T (rs405509) and +113G>C (rs440446) in APOE gene had shown association with plasma apoE concentrations (Lambert et al, 2000;Moreno et al, 2003), insulin resistance (Viitanen et al, 2001), insulin sensitivity in response to a diet rich in satured fats (Moreno et al, 2005). In a cross-sectional study, the impacts of these polymorphisms have been analyzed on lipid, apolipoprotein, glucose, and serum insulin concentrations in the TARF cohort, a representative of Turkish adults.…”