An angiotensin converting enzyme haplotype predicts survival in patients with end stage renal disease

James B. Wetmore, Kirsten L. Johansen, Saunak Sen, Adriana M. Hung, David H. Lovett

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The renin-angiotensin system is implicated in the development of a variety of human diseases. Many studies have sought to characterize the clinical implications of polymorphisms in the angiotensin converting enzyme (ACE) gene. Given the high mortality rate of individuals on chronic hemodialysis (HD), we sought to investigate whether genetic diversity in the ACE gene correlates with mortality in this population. We assembled a racially diverse cohort of prevalent individuals on chronic outpatient HD, and followed it prospectively for a mean of 2.1 years. Subjects were genotyped for seven single nucleotide polymorphisms (SNPs) in the ACE gene. Haplotype probabilities were calculated using an expectation-maximization algorithm. Cox proportional hazards regression was used to determine associations between haplotype and time to mortality from initiation of HD. There was strong linkage disequilibrium (LD) across the ACE gene, with three tagging SNPs found to account for all seven-SNP haplotypes that had a frequency of greater than 4%. After adjustment for age, race, gender, and diabetes status, a three-locus haplotype was associated with a 72% risk reduction in mortality (P = 0.004). The majority of this association was captured by the TT genotype of A-239T promoter polymorphism. The TGG (non-wild-type) haplotype, consisting of three tagging SNPs in the ACE gene, is associated with significantly decreased risk of all-cause mortality in HD patients independent of age, race, gender, and diabetic status. This "protective" haplotype may encompass loci with functional significance in the ACE gene.

Original languageEnglish (US)
Pages (from-to)201-210
Number of pages10
JournalHuman Genetics
Volume120
Issue number2
DOIs
StatePublished - Sep 1 2006

Fingerprint

Peptidyl-Dipeptidase A
Haplotypes
Chronic Kidney Failure
Single Nucleotide Polymorphism
Survival
Renal Dialysis
Mortality
Genes
Linkage Disequilibrium
Risk Reduction Behavior
Renin-Angiotensin System
Outpatients
Genotype
Population

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

An angiotensin converting enzyme haplotype predicts survival in patients with end stage renal disease. / Wetmore, James B.; Johansen, Kirsten L.; Sen, Saunak; Hung, Adriana M.; Lovett, David H.

In: Human Genetics, Vol. 120, No. 2, 01.09.2006, p. 201-210.

Research output: Contribution to journalArticle

Wetmore, James B. ; Johansen, Kirsten L. ; Sen, Saunak ; Hung, Adriana M. ; Lovett, David H. / An angiotensin converting enzyme haplotype predicts survival in patients with end stage renal disease. In: Human Genetics. 2006 ; Vol. 120, No. 2. pp. 201-210.
@article{be92979c28434569bc69c6341605fccc,
title = "An angiotensin converting enzyme haplotype predicts survival in patients with end stage renal disease",
abstract = "The renin-angiotensin system is implicated in the development of a variety of human diseases. Many studies have sought to characterize the clinical implications of polymorphisms in the angiotensin converting enzyme (ACE) gene. Given the high mortality rate of individuals on chronic hemodialysis (HD), we sought to investigate whether genetic diversity in the ACE gene correlates with mortality in this population. We assembled a racially diverse cohort of prevalent individuals on chronic outpatient HD, and followed it prospectively for a mean of 2.1 years. Subjects were genotyped for seven single nucleotide polymorphisms (SNPs) in the ACE gene. Haplotype probabilities were calculated using an expectation-maximization algorithm. Cox proportional hazards regression was used to determine associations between haplotype and time to mortality from initiation of HD. There was strong linkage disequilibrium (LD) across the ACE gene, with three tagging SNPs found to account for all seven-SNP haplotypes that had a frequency of greater than 4{\%}. After adjustment for age, race, gender, and diabetes status, a three-locus haplotype was associated with a 72{\%} risk reduction in mortality (P = 0.004). The majority of this association was captured by the TT genotype of A-239T promoter polymorphism. The TGG (non-wild-type) haplotype, consisting of three tagging SNPs in the ACE gene, is associated with significantly decreased risk of all-cause mortality in HD patients independent of age, race, gender, and diabetic status. This {"}protective{"} haplotype may encompass loci with functional significance in the ACE gene.",
author = "Wetmore, {James B.} and Johansen, {Kirsten L.} and Saunak Sen and Hung, {Adriana M.} and Lovett, {David H.}",
year = "2006",
month = "9",
day = "1",
doi = "10.1007/s00439-006-0191-4",
language = "English (US)",
volume = "120",
pages = "201--210",
journal = "Human Genetics",
issn = "0340-6717",
publisher = "Springer Verlag",
number = "2",

}

TY - JOUR

T1 - An angiotensin converting enzyme haplotype predicts survival in patients with end stage renal disease

AU - Wetmore, James B.

AU - Johansen, Kirsten L.

AU - Sen, Saunak

AU - Hung, Adriana M.

AU - Lovett, David H.

PY - 2006/9/1

Y1 - 2006/9/1

N2 - The renin-angiotensin system is implicated in the development of a variety of human diseases. Many studies have sought to characterize the clinical implications of polymorphisms in the angiotensin converting enzyme (ACE) gene. Given the high mortality rate of individuals on chronic hemodialysis (HD), we sought to investigate whether genetic diversity in the ACE gene correlates with mortality in this population. We assembled a racially diverse cohort of prevalent individuals on chronic outpatient HD, and followed it prospectively for a mean of 2.1 years. Subjects were genotyped for seven single nucleotide polymorphisms (SNPs) in the ACE gene. Haplotype probabilities were calculated using an expectation-maximization algorithm. Cox proportional hazards regression was used to determine associations between haplotype and time to mortality from initiation of HD. There was strong linkage disequilibrium (LD) across the ACE gene, with three tagging SNPs found to account for all seven-SNP haplotypes that had a frequency of greater than 4%. After adjustment for age, race, gender, and diabetes status, a three-locus haplotype was associated with a 72% risk reduction in mortality (P = 0.004). The majority of this association was captured by the TT genotype of A-239T promoter polymorphism. The TGG (non-wild-type) haplotype, consisting of three tagging SNPs in the ACE gene, is associated with significantly decreased risk of all-cause mortality in HD patients independent of age, race, gender, and diabetic status. This "protective" haplotype may encompass loci with functional significance in the ACE gene.

AB - The renin-angiotensin system is implicated in the development of a variety of human diseases. Many studies have sought to characterize the clinical implications of polymorphisms in the angiotensin converting enzyme (ACE) gene. Given the high mortality rate of individuals on chronic hemodialysis (HD), we sought to investigate whether genetic diversity in the ACE gene correlates with mortality in this population. We assembled a racially diverse cohort of prevalent individuals on chronic outpatient HD, and followed it prospectively for a mean of 2.1 years. Subjects were genotyped for seven single nucleotide polymorphisms (SNPs) in the ACE gene. Haplotype probabilities were calculated using an expectation-maximization algorithm. Cox proportional hazards regression was used to determine associations between haplotype and time to mortality from initiation of HD. There was strong linkage disequilibrium (LD) across the ACE gene, with three tagging SNPs found to account for all seven-SNP haplotypes that had a frequency of greater than 4%. After adjustment for age, race, gender, and diabetes status, a three-locus haplotype was associated with a 72% risk reduction in mortality (P = 0.004). The majority of this association was captured by the TT genotype of A-239T promoter polymorphism. The TGG (non-wild-type) haplotype, consisting of three tagging SNPs in the ACE gene, is associated with significantly decreased risk of all-cause mortality in HD patients independent of age, race, gender, and diabetic status. This "protective" haplotype may encompass loci with functional significance in the ACE gene.

UR - http://www.scopus.com/inward/record.url?scp=33747000019&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33747000019&partnerID=8YFLogxK

U2 - 10.1007/s00439-006-0191-4

DO - 10.1007/s00439-006-0191-4

M3 - Article

VL - 120

SP - 201

EP - 210

JO - Human Genetics

JF - Human Genetics

SN - 0340-6717

IS - 2

ER -