Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
10528248
TITLE
Exclusion of angiotensinogen gene in molecular basis of human hypertension: sibpair linkage and association analyses in Australian anglo-caucasians.
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.
Copyright 1999 Wiley-Liss, Inc.
DATE PUBLISHED
1999 Nov 5
HISTORY
PUBSTATUS PUBSTATUSDATE
pubmed 1999/10/21
medline 1999/10/21 00:01
entrez 1999/10/21 00:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Wang WY Wang W Y WY Hypertension Gene Laboratory, Department of Physiology and Institute for Biomedical Research, The University of Sydney, Sydney, New South Wales, Australia.
Glenn CL Glenn C L CL
Zhang W Zhang W W
Benjafield AV Benjafield A V AV
Nyholt DR Nyholt D R DR
Morris BJ Morris B J BJ
INVESTIGATORS
JOURNAL
VOLUME: 87
ISSUE: 1
TITLE: American journal of medical genetics
ISOABBREVIATION: Am. J. Med. Genet.
YEAR: 1999
MONTH: Nov
DAY: 5
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Print
ISSN: 0148-7299
ISSNTYPE: Print
MEDLINE JOURNAL
MEDLINETA: Am J Med Genet
COUNTRY: United States
ISSNLINKING: 0148-7299
NLMUNIQUEID: 7708900
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
GRANTS
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adult
Aged
Alleles
Angiotensinogen genetics
Australia genetics
European Continental Ancestry Group genetics
Family Health genetics
Female genetics
Gene Frequency genetics
Genetic Linkage genetics
Genotype genetics
Haplotypes genetics
Humans genetics
Hypertension genetics
Linkage Disequilibrium genetics
Male genetics
Microsatellite Repeats genetics
Middle Aged genetics
Nuclear Family genetics
Polymorphism, Genetic genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
11002-13-4 Angiotensinogen
OTHER ID's