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 journalArticle

5 Citations (Scopus)

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
StatePublished - Jun 2006
Externally publishedYes

Fingerprint

Mexican Americans
Aryldialkylphosphatase
chromosome
quantitative trait loci
Quantitative Trait Loci
chromosomes
Chromosomes, Human, Pair 22
enzyme
loci
antioxidant
serum
genome
Chromosomes, Human, Pair 19
aryldialkylphosphatase
Chromosomes, Human, Pair 12
decomposition
Chromosomes, Human, Pair 17
Chromosomes, Human, Pair 7
Papio
Poisons

Keywords

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

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Genetics
  • Genetics(clinical)
  • Ecology, Evolution, Behavior and Systematics

Cite this

Winnier, D. A., Rainwater, D. L., Cole, S. A., Dyer, T. D., Blangero, J., MacCluer, J. W., & Mahaney, M. C. (2006). Multiple QTLs influence variation in paraoxonase 1 activity in Mexican Americans. Human Biology, 78(3), 341-352.

Multiple QTLs influence variation in paraoxonase 1 activity in Mexican Americans. / Winnier, Deidre A.; Rainwater, David L.; Cole, Shelley A.; Dyer, Thomas D.; Blangero, John; MacCluer, Jean W.; Mahaney, Michael C.

In: Human Biology, Vol. 78, No. 3, 06.2006, p. 341-352.

Research output: Contribution to journalArticle

Winnier, DA, Rainwater, DL, Cole, SA, Dyer, TD, Blangero, J, MacCluer, JW & Mahaney, MC 2006, 'Multiple QTLs influence variation in paraoxonase 1 activity in Mexican Americans', Human Biology, vol. 78, no. 3, pp. 341-352.
Winnier DA, Rainwater DL, Cole SA, Dyer TD, Blangero J, MacCluer JW et al. Multiple QTLs influence variation in paraoxonase 1 activity in Mexican Americans. Human Biology. 2006 Jun;78(3):341-352.
Winnier, Deidre A. ; Rainwater, David L. ; Cole, Shelley A. ; Dyer, Thomas D. ; Blangero, John ; MacCluer, Jean W. ; Mahaney, Michael C. / Multiple QTLs influence variation in paraoxonase 1 activity in Mexican Americans. In: Human Biology. 2006 ; Vol. 78, No. 3. pp. 341-352.
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