ASSOCIATIONS OF CANDIDATE LOCI ANGIOTENSINOGEN AND ANGIOTENSIN-CONVERTING ENZYME WITH SEVERE HYPERTENSION - THE NHLBI FAMILY HEART-STUDY

PURPOSE: In studies conducted in several different populations, the M2 35T substitution in the antiotensinogen (AGT) locus has been associate d with hypertension. METHODS: A case-control study was initiated in an attempt to replicate this finding. Persons with hypertension, age- an d sex-matched normotensive controls, and randomly sampled individuals were probands from the Family Heart Study of the National Heart, Lung, and Blood Institute. Subjects were recruited from the Atherosclerosis Risk in Communities study (ARIC) in North Carolina and Minneapolis, M N, and from the Framingham Heart Study in Massachusetts. Genotypes wer e determined for the M235T substitution in the AGT locus and for the i nsertion/deletion polymorphism in the angiotensin-converting enzyme (A CE) locus. Simple association tests as well as logistic regression ana lyses were performed. RESULTS: The association of AGT-T235 with hypert ension was replicated in the Framingham sample (odds ratio, 1.60; 95% confidence interval, 1.11-2.30), but not in the ARIC white or black su bjects. However, logistic regression analysis suggested a significant association of AGT with hypertension in both the ARIC white and Framin gham samples when the effects of body mass index, triglycerides, and t he presence of significant coronary heart disease were controlled. The se analyses further suggested that, in the ARIC data, the relationship with the AGT locus is stronger in women than men and that there may b e interaction (epistasis) between homozygotes for T235 and ACE-DD in t he Framingham data. While the small sample size precluded logistic reg ression analysis, the frequency of the T235 allele in the black random sample was much higher than in the comparable white sample. CONCLUSIO NS: These results are compatible with the presence of a genetic risk f actor for hypertension in or near the angiotensinogen locus. (C) 1997 by Elsevier Science Inc.