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Titolo:
HAPLOTYPES OF ANGIOTENSINOGEN IN ESSENTIAL-HYPERTENSION
Autore:
JEUNEMAITRE X; INOUE I; WILLIAMS C; CHARRU A; TICHET J; POWERS M; SHARMA AM; GIMENEZROQUEPLO AP; HATA A; CORVOL P; LALOUEL JM;
Indirizzi:
HOP BROUSSAIS,GENET MOL LAB,ASSISTANCE PUBL HOP PARIS,96 RUE DIDOT,ILOT MARINIERS 2 ETAGE F-75014 PARIS FRANCE COLL FRANCE,INSERM U36 F-75231 PARIS FRANCE UNIV UTAH,HLTH SCI CTR,DEPT HUMAN GENET SALT LAKE CITY UT 84132 INST REG SANTE LA RICHE FRANCE FREE UNIV BERLIN,DEPT GEN INTERNAL MED & NEPHROL D-1000 BERLIN GERMANY HOKKAIDO UNIV,SCH MED,DEPT PUBL HLTH SAPPORO HOKKAIDO 060 JAPAN
Titolo Testata:
American journal of human genetics
fascicolo: 6, volume: 60, anno: 1997,
pagine: 1448 - 1460
SICI:
0002-9297(1997)60:6<1448:HOAIE>2.0.ZU;2-2
Fonte:
ISI
Lingua:
ENG
Soggetto:
ENHANCER CORE ELEMENT; BLOOD-PRESSURE; MET(235)->THR VARIANT; FAMILIAL HYPERTENSION; MYOCARDIAL-INFARCTION; MOLECULAR VARIANT; GENE; POLYMORPHISM; ASSOCIATION; JAPANESE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
50
Recensione:
Indirizzi per estratti:
Citazione:
X. Jeunemaitre et al., "HAPLOTYPES OF ANGIOTENSINOGEN IN ESSENTIAL-HYPERTENSION", American journal of human genetics, 60(6), 1997, pp. 1448-1460

Abstract

The M235T polymorphism of the angiotensinogen gene (AGT) has been associated with essential and pregnancy-induced hypertension. Generation of haplotypes can help to resolve whether the T235 allele itself predisposes to the development of hypertension or acts as a marker of an unknown causal molecular variant. We identified 10 diallelic polymorphisms at the AGT locus and genotyped both a series of 477 probands of hypertensive families and 364 controls, all French Caucasians, as well asa series of 92 hypertensives and 122 controls from Japan. Despite a large ethnic difference in gene frequency, a significant association ofT235 with hypertension was observed both in Caucasians (.46 vs. .38, P = .004) and in Japanese (.91 vs. .76, P = .002). In both groups, theG-->A substitution located at position -6 upstream of the initial transcription site occurred at the same frequency and in complete linkagedisequilibrium with the T235 allele. No other polymorphism was found to be consistently associated with hypertension. Five informative haplotypes subdividing the T235 allele were generated. Whereas two of themwere associated with hypertension in Caucasians, none of these two haplotypes (H3 and H4) reached statistical significance in Japanese. Theanalysis of the AGT-GT repeat revealed marked linkage disequilibriumsbetween each of the diallelic polymorphisms and some (GT)(16) alleles, with similar patterns in the two populations. The strong disequilibrium between M235 and (GT)(16) explained the increased frequency of that particular allele in French controls compared with hypertensives (.42 vs. .36, P < .01). The haplotype combining the M235T and G-GA polymorphisms appears as the ancestral allele of the human AGT gene and as the one associated with hypertension.

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Documento generato il 20/01/21 alle ore 15:59:44