Liver X receptor alpha associates with human life span.

Authors: Mooijaart SP; Kuningas M; Westendorp RG; Houwing-Duistermaat JJ; Slagboom PE; Rensen PC; van Heemst D

Abstract: In the nematode Caenorhabditis elegans, nuclear hormone receptor DAF-12 regulates the decision to go into a resistant dauer diapause, in which the worm exhibits a decreased rate of aging. Using sequence similarity searches, we previously identified the liver X receptor alpha (LXRalpha) as one of the human nuclear hormone receptors the protein sequence of which is most similar to C. elegans DAF-12. Here, we studied whether variation in the gene encoding LXRalpha associates with human life span. In the Leiden 85-Plus Study, a population-based prospective follow-up study, we genotyped four polymorphisms spanning the gene coding for LXRalpha (NR1H3) and tagged four common haplotypes. Among 563 participants, haplotype 2 associated with reduced mortality during the 7-year follow-up (hazard ratio 0.78; p =.015), predominantly caused by reduced mortality from infectious disease (hazard ratio 0.31; p =.023). Haplotype 2 also associated with higher levels of plasma apolipoprotein E, a target gene of the LXRalpha (p =.018), and higher levels of triglycerides (p =.041). Genetic variation in the gene coding for the LXRalpha (NR1H3) associates with human life span.

Keywords: Aged, 80 and over; Apolipoproteins E/blood; Cause of Death; Cohort Studies; DNA-Binding Proteins/*genetics; Female; Follow-Up Studies; Genetic Variation; Haplotypes; Humans; Infection/mortality; *Longevity; Male; Orphan Nuclear Receptors; Polymorphism, Genetic; Proportional Hazards Models; Prospective Studies; Receptors, Cytoplasmic and Nuclear/*genetics; Triglycerides/blood
Journal: The journals of gerontology. Series A, Biological sciences and medical sciences
Volume: 62
Issue: 4
Pages: 343-9
Date: April 25, 2007
PMID: 17452725
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Citation:

Mooijaart SP, Kuningas M, Westendorp RG, Houwing-Duistermaat JJ, Slagboom PE, Rensen PC, van Heemst D (2007) Liver X receptor alpha associates with human life span. The journals of gerontology. Series A, Biological sciences and medical sciences 62: 343-9.


Longevity Variant Associations (p-value):
  • rs11039149 (0.015)

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