Evidence for a familial pregnancy-induced hypertension locus in the eNOS-gene region

Reynir Arngrímsson; Caroline Hayward; Sophie Nadaud; Ásdis Baldursdóttir; James J. Walker; Wang A. Liston; Ragnheidur I. Bjarnadóttir; David J.H. Brock; Reynir T. Geirsson; J. Michael Connor; Florent Soubrier

doi:10.1086/514843

Evidence for a familial pregnancy-induced hypertension locus in the eNOS-gene region

Reynir Arngrímsson^*, Caroline Hayward, Sophie Nadaud, Ásdis Baldursdóttir, James J. Walker, Wang A. Liston, Ragnheidur I. Bjarnadóttir, David J.H. Brock, Reynir T. Geirsson, J. Michael Connor, Florent Soubrier

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

117 Citations (Scopus)

Abstract

Pregnancy-induced hypertension may be regarded as a manifestation of endothelial-cell dysfunction. The role of the eNOS gene in the development of a familial pregnancy-induced hypertension was evaluated by analysis of linkage among affected sisters and in multiplex families (n = 50). Markers from a 4-cM region encoding the eNOS gene showed distortion from the expected allele sharing among affected sisters (P = .001-.05), and the statistic obtained from the multilocus application of the affected-pedigree-member method also showed distortion (T([f(P)=sqrt(P)])= 3.53; P < .001). A LOD score of 3.36 was obtained for D7S505 when a best-fitting model derived from genetic epidemiological data was used, and LOD scores of 2.54-4.03 were obtained when various other genetic models were used. Estimates of recombination rate, rather than maximum LOD-score values, were affected by changes in the genetic parameters. The transmission-disequilibrium test, a model-free estimate of linkage, showed strongest association and linkage with a microsatellite within intron 13 of the eNOS gene (P = .005). These results support the localization of a familial pregnancy-induced hypertension- susceptibility locus in the region of chromosome 7q36 encoding the eNOS gene.

Original language	English
Pages (from-to)	354-362
Number of pages	9
Journal	American Journal of Human Genetics
Volume	61
Issue number	2
DOIs	https://doi.org/10.1086/514843
Publication status	Published - Aug 1997

Bibliographical note

Funding Information:
We wish to acknowledge the help and contribution of Dr. S. Björnsson, Ms. H. Cheyne, Mrs. L. Glasgow and Mrs. B. O’Hare in Glasgow, Ms. I. Ferry in Paris, and Dr. L. S. Jónsdót-tir and the staff at the Heart Preventive Clinic in Reykjavík. This work is supported by the Wellcome Trust (support to R.A.), the Science Foundation of Iceland, and the Research Fund of the University of Iceland. The support of INSERM, by a grant from the Groupement de Recherche et d’Études sur les Genomes (GREG), and of European Community concerted action CT94-1353 is also gratefully acknowledged. J. Terwil-liger has kindly given advice on SIBPAIR and TDT analyses and has allowed access to his genetic analysis package, ANALYZE, and A. A. Schäffer has allowed access to the FASTLINK linkage programs.

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10.1086/514843

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@article{723e32313a53479482e051545291e6f7,

title = "Evidence for a familial pregnancy-induced hypertension locus in the eNOS-gene region",

abstract = "Pregnancy-induced hypertension may be regarded as a manifestation of endothelial-cell dysfunction. The role of the eNOS gene in the development of a familial pregnancy-induced hypertension was evaluated by analysis of linkage among affected sisters and in multiplex families (n = 50). Markers from a 4-cM region encoding the eNOS gene showed distortion from the expected allele sharing among affected sisters (P = .001-.05), and the statistic obtained from the multilocus application of the affected-pedigree-member method also showed distortion (T([f(P)=sqrt(P)])= 3.53; P < .001). A LOD score of 3.36 was obtained for D7S505 when a best-fitting model derived from genetic epidemiological data was used, and LOD scores of 2.54-4.03 were obtained when various other genetic models were used. Estimates of recombination rate, rather than maximum LOD-score values, were affected by changes in the genetic parameters. The transmission-disequilibrium test, a model-free estimate of linkage, showed strongest association and linkage with a microsatellite within intron 13 of the eNOS gene (P = .005). These results support the localization of a familial pregnancy-induced hypertension- susceptibility locus in the region of chromosome 7q36 encoding the eNOS gene.",

author = "Reynir Arngr{\'i}msson and Caroline Hayward and Sophie Nadaud and {\'A}sdis Baldursd{\'o}ttir and Walker, {James J.} and Liston, {Wang A.} and Bjarnad{\'o}ttir, {Ragnheidur I.} and Brock, {David J.H.} and Geirsson, {Reynir T.} and Connor, {J. Michael} and Florent Soubrier",

note = "Funding Information: We wish to acknowledge the help and contribution of Dr. S. Bj{\"o}rnsson, Ms. H. Cheyne, Mrs. L. Glasgow and Mrs. B. O{\textquoteright}Hare in Glasgow, Ms. I. Ferry in Paris, and Dr. L. S. J{\'o}nsd{\'o}t-tir and the staff at the Heart Preventive Clinic in Reykjav{\'i}k. This work is supported by the Wellcome Trust (support to R.A.), the Science Foundation of Iceland, and the Research Fund of the University of Iceland. The support of INSERM, by a grant from the Groupement de Recherche et d{\textquoteright}{\'E}tudes sur les Genomes (GREG), and of European Community concerted action CT94-1353 is also gratefully acknowledged. J. Terwil-liger has kindly given advice on SIBPAIR and TDT analyses and has allowed access to his genetic analysis package, ANALYZE, and A. A. Sch{\"a}ffer has allowed access to the FASTLINK linkage programs.",

year = "1997",

month = aug,

doi = "10.1086/514843",

language = "English",

volume = "61",

pages = "354--362",

journal = "American Journal of Human Genetics",

issn = "0002-9297",

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T1 - Evidence for a familial pregnancy-induced hypertension locus in the eNOS-gene region

AU - Arngrímsson, Reynir

AU - Hayward, Caroline

AU - Nadaud, Sophie

AU - Baldursdóttir, Ásdis

AU - Walker, James J.

AU - Liston, Wang A.

AU - Bjarnadóttir, Ragnheidur I.

AU - Brock, David J.H.

AU - Geirsson, Reynir T.

AU - Connor, J. Michael

AU - Soubrier, Florent

N1 - Funding Information: We wish to acknowledge the help and contribution of Dr. S. Björnsson, Ms. H. Cheyne, Mrs. L. Glasgow and Mrs. B. O’Hare in Glasgow, Ms. I. Ferry in Paris, and Dr. L. S. Jónsdót-tir and the staff at the Heart Preventive Clinic in Reykjavík. This work is supported by the Wellcome Trust (support to R.A.), the Science Foundation of Iceland, and the Research Fund of the University of Iceland. The support of INSERM, by a grant from the Groupement de Recherche et d’Études sur les Genomes (GREG), and of European Community concerted action CT94-1353 is also gratefully acknowledged. J. Terwil-liger has kindly given advice on SIBPAIR and TDT analyses and has allowed access to his genetic analysis package, ANALYZE, and A. A. Schäffer has allowed access to the FASTLINK linkage programs.

PY - 1997/8

Y1 - 1997/8

N2 - Pregnancy-induced hypertension may be regarded as a manifestation of endothelial-cell dysfunction. The role of the eNOS gene in the development of a familial pregnancy-induced hypertension was evaluated by analysis of linkage among affected sisters and in multiplex families (n = 50). Markers from a 4-cM region encoding the eNOS gene showed distortion from the expected allele sharing among affected sisters (P = .001-.05), and the statistic obtained from the multilocus application of the affected-pedigree-member method also showed distortion (T([f(P)=sqrt(P)])= 3.53; P < .001). A LOD score of 3.36 was obtained for D7S505 when a best-fitting model derived from genetic epidemiological data was used, and LOD scores of 2.54-4.03 were obtained when various other genetic models were used. Estimates of recombination rate, rather than maximum LOD-score values, were affected by changes in the genetic parameters. The transmission-disequilibrium test, a model-free estimate of linkage, showed strongest association and linkage with a microsatellite within intron 13 of the eNOS gene (P = .005). These results support the localization of a familial pregnancy-induced hypertension- susceptibility locus in the region of chromosome 7q36 encoding the eNOS gene.

AB - Pregnancy-induced hypertension may be regarded as a manifestation of endothelial-cell dysfunction. The role of the eNOS gene in the development of a familial pregnancy-induced hypertension was evaluated by analysis of linkage among affected sisters and in multiplex families (n = 50). Markers from a 4-cM region encoding the eNOS gene showed distortion from the expected allele sharing among affected sisters (P = .001-.05), and the statistic obtained from the multilocus application of the affected-pedigree-member method also showed distortion (T([f(P)=sqrt(P)])= 3.53; P < .001). A LOD score of 3.36 was obtained for D7S505 when a best-fitting model derived from genetic epidemiological data was used, and LOD scores of 2.54-4.03 were obtained when various other genetic models were used. Estimates of recombination rate, rather than maximum LOD-score values, were affected by changes in the genetic parameters. The transmission-disequilibrium test, a model-free estimate of linkage, showed strongest association and linkage with a microsatellite within intron 13 of the eNOS gene (P = .005). These results support the localization of a familial pregnancy-induced hypertension- susceptibility locus in the region of chromosome 7q36 encoding the eNOS gene.

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DO - 10.1086/514843

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VL - 61

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EP - 362

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

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ER -

Evidence for a familial pregnancy-induced hypertension locus in the eNOS-gene region

Abstract

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