A genome scan for renal function among hypertensives

The HyperGEN study

Andrew T. DeWan, Donna K. Arnett, Larry D. Atwood, Michael A. Province, Cora E. Lewis, Steven Hunt, John Eckfeldt

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

Decreased renal function is often a complication of hypertension. Although it has been suggested that the response of the kidney to hypertension has an underlying genetic component, there is limited information suggesting that specific genetic regions or candidate genes contribute to the variability in creatinine clearance, a commonly used measure of kidney function. As part of the Hypertension Genetic Epidemiology Network (HyperGEN) study, creatinine clearance measurements were assessed in a large biracial sample of hypertensive siblings (466 African American subjects and 634 white subjects in 215 and 265 sibships, respectively). All participants were hypertensive before the age of 60 years, and the mean age of the siblings was 52 years among the African American subjects and 61 years among the white subjects. Two residual models were created for creatinine clearance: a minimally adjusted model (which included age and age2) and a fully adjusted model (which included age, age2, lean body mass, pulse rate, pulse pressure, hormone-replacement therapy, educational status, and physical activity). Standardized residuals were calculated separately for men and women in both racial groups. The heritability of the residual creatinine clearance was 17% and 18% among the African American and white subjects, respectively. We conducted multipoint variance components linkage analysis using GENEHUNTER2 and 387 anonymous markers (Cooperative Human Linkage Center screening set 8). The best evidence for linkage in African American subjects was found on chromosome 3 (LOD = 3.61 at 214.6 cM, 3q27) with the fully adjusted model, and the best evidence in white subjects was found on chromosome 3 (LOD = 3.36 at 115.1 cM) with the minimally adjusted model. Positional candidate genes that are contained in and around the region on chromosome 3 (214.6 cM) that may contribute to renal function include enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase (EHHADH) and apolipoprotein D (ApoD). These findings suggest there may be genetic regions related to the variability of creatinine clearance among hypertensive individuals.

Original languageEnglish
Pages (from-to)136-144
Number of pages9
JournalAmerican Journal of Human Genetics
Volume68
Issue number1
DOIs
Publication statusPublished - 2001
Externally publishedYes

Fingerprint

Molecular Epidemiology
Creatinine
African Americans
Chromosomes, Human, Pair 3
Genome
Hypertension
Kidney
Siblings
Apolipoproteins D
Enoyl-CoA Hydratase
3-Hydroxyacyl-CoA Dehydrogenase
Educational Status
Hormone Replacement Therapy
Genes
Heart Rate
Exercise
Blood Pressure
Education

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

DeWan, A. T., Arnett, D. K., Atwood, L. D., Province, M. A., Lewis, C. E., Hunt, S., & Eckfeldt, J. (2001). A genome scan for renal function among hypertensives: The HyperGEN study. American Journal of Human Genetics, 68(1), 136-144. https://doi.org/10.1086/316927

A genome scan for renal function among hypertensives : The HyperGEN study. / DeWan, Andrew T.; Arnett, Donna K.; Atwood, Larry D.; Province, Michael A.; Lewis, Cora E.; Hunt, Steven; Eckfeldt, John.

In: American Journal of Human Genetics, Vol. 68, No. 1, 2001, p. 136-144.

Research output: Contribution to journalArticle

DeWan, AT, Arnett, DK, Atwood, LD, Province, MA, Lewis, CE, Hunt, S & Eckfeldt, J 2001, 'A genome scan for renal function among hypertensives: The HyperGEN study', American Journal of Human Genetics, vol. 68, no. 1, pp. 136-144. https://doi.org/10.1086/316927
DeWan, Andrew T. ; Arnett, Donna K. ; Atwood, Larry D. ; Province, Michael A. ; Lewis, Cora E. ; Hunt, Steven ; Eckfeldt, John. / A genome scan for renal function among hypertensives : The HyperGEN study. In: American Journal of Human Genetics. 2001 ; Vol. 68, No. 1. pp. 136-144.
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