Multiple QTLs influence variation in paraoxonase 1 activity in Mexican Americans

Deidre A. Winnier, David L. Rainwater, Shelley A. Cole, Thomas D. Dyer, John Blangero, Jean W. MacCluer, Michael C. Mahaney

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Paraoxonase 1 (PON1), a high-density-lipoprotein-associated enzyme known to protect against cellular damage from toxic agents, may also have antioxidant properties. Although the importance of the influence of the PON1 structural locus on chromosome 7q21-22 for variation in the concentration and activity of the enzyme is well-documented, the contribution of other loci is poorly understood. Based on the recent observations of at least one additional quantitative trait locus (QTL) for PON1 activity in pedigreed baboons, we conducted a whole-genome linkage screen for QTLs other than the PON1 structural locus that may influence PON1 activity in humans. We measured PON1 activity in frozen serum for 1,406 individuals in more than 40 extended pedigrees from the San Antonio Family Heart Study (SAFHS). We used a maximum-likelihood-based variance decomposition approach implemented in SOLAR to test for QTLs that may influence PON1 activity. In addition to a QTL for which we detected the strongest, significant evidence (LOD = 31.41) at or near the PON1 structural locus on chromosome 7q21-22, we also localized at least one additional significant QTL on chromosome 12 (LOD = 3.56). Furthermore, we detected suggestive evidence for two more PON-related QTLs on chromosomes 17 and 19. We have provided evidence that other genes, in addition to the well-known ones on chromosome 7, play a role in influencing normal variation in PON1 activity.

Original languageEnglish (US)
Pages (from-to)341-352
Number of pages12
JournalHuman Biology
Volume78
Issue number3
DOIs
StatePublished - Jun 2006

Keywords

  • Cardiovascular disease
  • Humans
  • Oxidative stress
  • Paraoxonase 1 (PON1)
  • QTL linkage analysis
  • San Antonio Family Heart Study (SAFHS)

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Genetics
  • Genetics(clinical)

Fingerprint Dive into the research topics of 'Multiple QTLs influence variation in paraoxonase 1 activity in Mexican Americans'. Together they form a unique fingerprint.

Cite this