Intron 4 polymorphism of the endothelial nitric oxide synthase gene is associated with elevated blood pressure in type 2 diabetic patients with coronary heart disease

The endothelial nitric oxide synthase (eNOS) gene is responsible for consti tutive nitric oxide synthesis and arterial vasodilatation. Recently two pol ymorphisms, the 27-bp repeat sequence in intron 4 and the Glu298Asp substit ution in exon 7 of the eNOS gene have been reported to be related to corona ry heart disease (CHD). We screened these polymorphisms of the eNOS gene in 308 unrelated nondiabetic subjects with CHD, in 251 unrelated patients wit h type 2 diabetes with CHD, and in 110 randomly selected healthy subjects w ithout CHD. The 4a and Asp298 allele frequencies of the eNOS gene were 0.19 and 0.36 in nondiabetic patients with CHD, 0.21 and 0.27 in type 2 diabeti c patients with CHD, and 0.16 and 0.31 in nondiabetic subjects without CHD (n.s. between the groups). The Asp298 allele in exon 7 of the eNOS gene was not associated with elevated blood pressure in any of the study groups. Am ong type 2 diabetic patients with CHD the 4a allele in intron 4 of the eNOS gene was associated with elevated levels of systolic (P=0.035) and mean ar terial blood pressure (P=0.040). In nondiabetic subjects these associations were not statistically significant. When all study groups were pooled in s tatistical analysis the 4a allele of the eNOS gene was associated with elev ated diastolic (P=0.032) and mean (P=0.030) arterial blood pressure even af ter adjustment for confounding factors. We conclude that the 4a allele of t he eNOS gene is not associated with CHD or type 2 diabetes, but that it is related to elevated blood pressure levels particularly among type 2 diabeti c patients with CHD.