Exclusion of angiotensinogen gene in molecular basis of human hypertension: Sibpair linkage and association analyses in Australian anglo-caucasians

Wang, W. Y., Glenn, C. L., Zhang, W., Benjafield, A. V., Nyholt, D. R., & Morris, B. J. (1999) Exclusion of angiotensinogen gene in molecular basis of human hypertension: Sibpair linkage and association analyses in Australian anglo-caucasians. American Journal of Medical Genetics, 87(1), pp. 53-60.

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Abstract

Linkage with essential hypertension has been claimed for a microsatellite marker near the angiotensinogen gene (AGT; chromosome 1q42), as has association for the AGT variants M235T, G(-6)A and A(-20)C. To more rigorously evaluate AGT as a candidate gene for hypertension we performed sibpair analysis with multiple microsatellite markers surrounding this locus and using more sophisticated analysis programs. We also performed an association study of the AGT variants in unrelated subjects with a strong family history (two affected parents). For the linkage study, single and multiplex polymerase chain reaction (PCRs) and automated genescan analysis were conducted on DNA from 175 Australian Anglo-Celtic Caucasian hypertensives for the following markers: D1S2880-(2.1 cM)-D1S213-(2.8 cM)-D1S251-(6.5 cM)-AGT-(2.0 cM) -D1S235. Statistical evaluation of genotype data by nonparametric methods resulted in the following scores: Single-point analysis - SPLINK, P > 0.18; APM method, P > 0.25; ASPEX, MLOD < 0.28; SIB-PAIR, P > 0. 24; Multipoint analysis - MAPMAKER/SIBS, MLOD < 0.24; GENEHUNTER, P > 0.35. Exclusion scores of Lod -4.1 to -5.1 were obtained for these markers using MAPMAKER/SIBS for a lambda(s) of 1.6. The association study of G(-6)A, A(-20)C and M235T variants in 111 hypertensives with strong family history and 190 normotensives with no family history showed significant linkage disequilibrium between particular haplotypes, but we could find no association with hypertension. The present study therefore excludes AGT in the etiology of hypertension, at least in the population of Australian Anglo-Celtic Caucasians studied.

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ID Code: 92182
Item Type: Journal Article
Refereed: Yes
Additional Information: Wang, W Y
Glenn, C L
Zhang, W
Benjafield, A V
Nyholt, D R
Morris, B J
eng
Research Support, Non-U.S. Gov't
1999/10/21
Am J Med Genet. 1999 Nov 5;87(1):53-60.
Keywords: Adult, Aged, Alleles, Angiotensinogen/*genetics, Australia, European Continental Ancestry Group/genetics, Family Health, Female, Gene Frequency, Genetic Linkage, Genotype, Haplotypes, Humans, Hypertension/*genetics, Linkage Disequilibrium, Male, Microsatellite Repeats, Middle Aged, Nuclear Family, Polymorphism, Genetic
DOI: 10.1002/(SICI)1096-8628(19991105)87:1<53::AID-AJMG11>3.0.CO;2-I
ISSN: 0148-7299
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 1999 Wiley-Liss, Inc.
Deposited On: 27 Jan 2016 05:40
Last Modified: 27 Jan 2016 05:40

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