Abstract
A variant of the angiotensinogen gene, M235T, has been associated with essential hypertension in selected subjects from Paris, France and Salt Lake City, Utah. In the present report, we studied a population-based sample consisting of 104 subjects diagnosed with hypertension before age 60 and 195 matched normotensive individuals from Rochester, Minnesota. We determined whether there was a relationship between the M235T polymorphism of the angiotensinogen gene and the occurrence of essential hypertension using two methods. First, a contingency chi-square analysis was carried out to test for an association between the M235T polymorphism and hypertension status. Second, multivariable conditional logistic regression was used to determine whether variation at the M235T polymorphism was a significant predictor of the probability of having essential hypertension. We detected no statistically significant association between the M235T polymorphism and the occurrence of essential hypertension. In particular, the association was not significant in either gender or in a subset of severely hypertensive subjects requiring two or more anti-hypertensive medications. Furthermore, variation in the number of M235T alleles did not make a significant contribution to predicting the probability of having essential hypertension, either alone or in conjunction with other predictor variables. These results suggest that the contribution of variation in the angiotensinogen gene to the occurrence of essential hypertension is less than initially suspected, or may not be constant across populations.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Bennett CL, Schrader AP, Moris BJ (1993) Cross-sectional analysis of Met235→Thr variant of angiotensinogen gene in severe familial hypertension. Biochem Biophys Res Commun 197:833–839
Breslow NE, Day NE (1980) Statistical methods in cancer research, vol. 1. The analysis of case-control studies. International Agency on Cancer, Lyon, France, pp 248–279
Cain MD, Walters WA, Catt KJ (1971) Effects of oral contraceptive therapy on the-renin-angiotensin system. J Clin Endocrinol 33:671–676
Cambien F, Poirier O, Lecerf L, Evans A, Cambou JP, Arveiler D, Luc G, Bard JM, Bara L, Ricard S, Tiret L, Amouyel P, Alhenc-Gelas F, Soubrier F (1992) Deletion polymorphism in the gene for angiotensin-converting enzyme is a potent risk factor for myocardial infarction. Nature 359:641–644
Caulfield M, Lavender P, Farrall M, Munroe P, Lawson M, Turner P, Clark AJL (1994) Linkage of the angiotensinogen gene to essential hypertension. N Engl J Med 330: 1629–1633
Deeb SS, Failor RA, Brown BG, Brunzell JD, Albers JJ, Motulsky AG, Wijsman E (1992) Association of apolipoprotein B gene variants with plasma apoB and low density lipoprotein (LDL) cholesterol levels. Hum Genet 88:463–470
Fasola AF, Martz BL, Helmer OM (1968) Plasma renin activity during supine exercise in offspring of hypertensive parents. J Appl Physiol 25:410–415
Gardes J, Bouhnik J, Clauser E, Corvol P, Ménard J (1989) Role of angiotensinogen in blood pressure homeostasis. Hypertension 4:185–189
Hosmer DH, Lemeshow S (1989) Applied logistic regression. Wiley, New York, pp 187–215
Jeunemaitre X, Soubrier F, Kotelevtsev YV, Lifton RP, Williams CS, Charru A, Hunt SC, Hopkins PN, Williams RR, Lalouel JM, Corvol P (1992) Molecular basis of human hypertension: role of angiotensinogen. Cell 71:169–180
Jeunemaitre X, Charru A, Chatellier G, Dumont C, Sassano P, Soubrier F, Ménard J, Corvol P (1993) M235T variant of the human angiotensinogen gene in unselected hypertensive patients. J Hypertens 11:S80-S81
Kaplan NM (1994) Clinical hypertension, 6th edn. Williams and Wilkins, Baltimore, pp 12–13
Kimura S, Mullins JJ, Bunnemann B, Metzger R, Hilgenfeldt U, Zimmermann F, Jacob H, Fuxe K, Ganten D, Kaling M (1992) High blood pressure in transgenic mice carrying the rat angiotensinogen gene. EMBO J 11:821–827
Ménard J, El Amrani AK, Savoie F, Bouhnik J (1991) Angiotensinogen: an attractive but underrated participant in hypertension and inflammation. Hypertension 18:705–706
Orita M, Iwahana H, Kanazawa H, Hayashi K, Sekiya T (1989) Detection of polymorphisms of human DNA by gel electrophoresis as single-strand conformation polymorphisms. Proc Natl Acad Sci USA 86:2766–2770
Templeton A, Boerwinkle E, Sing CF (1987) A cladistic analysis of phenotypic associations with haplotypes inferred from restriction nuclease mapping. I. Basic theory and an analysis of alcohol dehydrogenase activity in Drosophila. Genetics 117:343–351
Turner ST, Johnson M, Boerwinkle E, Richelson E, Taswell HF, Sing CF (1985) Sodium-lithium countertransport and blood pressure in healthy blood donors. Hypertension 7:955–962
Turner ST, Weidman WH, Michels VV, Reed TJ, Ormson CL, Fuller T, Sing CF (1989) Distribution of sodium-lithium countertransport in Caucasians nine to eighty-nine years of age. Hypertension 13:378–391
Turner ST, Michels VV (1991) Sodium-lithium countertransport and hypertension in Rochester, Minnesota. Hypertension 18:183–190
Turner ST, Rebbeck TR, Sing CF (1992) Sodium-lithium countertransport and probability of hypertension in Caucasians 47 to 89 years old. Hypertension 20:841–850
Walker WG, Whelton PK, Saito H, Russel RP, Hermann J (1979) Relation between blood pressure and renin, renin substrate, angiotensin II, aldosterone and urinary sodium and potassium in 574 ambulatory subjects. Hypertension 1:287–291
Ward K, Hata A, Jeunemaitre X, Helin C, Nelson C, Namikawa C, Farrington PF, Ogasawara M, Suzumori K, Tomoda S, Berrebi S, Sasaki M, Corvol P, Lifton RP, Lalouel JM (1993) A molecular variant of angiotensinogen associated with preeclampsia. Nat Gene 4:59–61
Ward R (1990) Familial aggregation and genetic epidemiology of blood pressure. In: Laragh JH, Brenner BM (eds) Hypertension: pathophysiology, diagnosis, and management. Raven Press, New York, pp 81–100
Watt GCM, Harrap SB, Foy CJW, Holton DW, Edwards HV, Davidson HR, Connor JM, Lever AF, Fraser R (1992) Abnormalities of glucocorticoid metabolism and the renin-angiotensin system: a four-corners approach to the identification of genetic determinants of blood pressure. J Hypertens 10:473–482
Williams RR, Hunt SC, Hopkins PN, Stults BM, Wu LL, Hassedt SJ, Barlow GK, Stephenson SH, Lalouel JM, Kuida H (1988) Familial dyslipidemic hypertension: evidence from 58 Utah families for a syndrome present in approximately 12% of patients with essential hypertension. JAMA 259:3579–3586
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Fornage, M., Turner, S.T., Sing, C.F. et al. Variation at the M235T locus of the angiotensinogen gene and essential hypertension: a population-based case-control study from Rochester, Minnesota. Hum Genet 96, 295–300 (1995). https://doi.org/10.1007/BF00210410
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00210410