Lack of association between angiotensinogen polymorphism (M235T) and cerebrovascular disease and carotid atheroma.
Genetic influences in cerebrovascular disease (CVD) may act either independently or by predisposing to, or modulating, the effect of risk factors such as hypertension. Factors involved in the pathogenesis of atherosclerosis, thrombosis and vasoconstriction are important in CVD. The angiotensinogen gene has recently been linked with essential hypertension in affected sibships and a particular polymorphism in exon 2 of the angiotensinogen gene, a threonine to methionine substitution at position 235 (M235T), has been associated with pre-eclampsia and hypertension. In this study we examined the relation of M235T polymorphism to cerebrovascular disease and carotid atheroma in 100 consecutive Caucasian patients with internal carotid artery territory ischaemia (TIA or stroke), presenting to a carotid ultrasound service. Forty five age-matched controls (mostly patients' spouses) were also studied. Hypertension was defined as current treatment with anti-hypertensive agents, or SBP > 160 mm Hg or DBP > 95 mm Hg. Twelve of 100 cases (12%) and eight of 45 controls (12%) were homozygous for the T235 allele. T:M allele ratios were 0.34:0.66 in cases and 0.34:0.66 in controls. There was no relation between the polymorphism and either internal carotid stenosis or common carotid artery intima-media thickness. In the cases, mean percentage internal carotid artery stenosis was TT 18.3 (SD 18.7)%, MT 38.0 (27.1)% and MM 36.8 (30.2)%. Mean intima-media thickness was TT 0.87 (0.18) mm, MT 0.95 (0.34) mm and MM 0.88 (0.23) mm. There was no relation between the polymorphism and hypertension (TT 11 of 100 cases, six of 45 controls).(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Child Health, St. George's Hospital Medical School, London, UK.
J
J
Barley
H
H
Markus
M
M
Brown
N
N
Carter
D000368:Aged; D000483:Alleles; D000704:Analysis of Variance; D000808:Angiotensinogen / Q000235:genetics* / Q000378:metabolism; D001161:Arteriosclerosis / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism; D016893:Carotid Stenosis / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D002561:Cerebrovascular Disorders / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006720:Homozygote; D006801:Humans; D006973:Hypertension / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D013912:Threonine; D018615:Ultrasonography, Doppler, Color
D000808:Angiotensinogen; D013912:Threonine