Liver X receptor alpha associates with human life span.
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.
Mooijaart
Simon P
SP
Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands. s.p.mooijaart@lumc.nl
Kuningas
Maris
M
Westendorp
Rudi G J
RG
Houwing-Duistermaat
Jeanine J
JJ
Slagboom
P Eline
PE
Rensen
Patrick C N
PC
van Heemst
Diana
D
D000369:Aged, 80 and over; D001057:Apolipoproteins E / Q000097:blood; D002423:Cause of Death; D015331:Cohort Studies; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D007239:Infections / Q000401:mortality; D000071518:Liver X Receptors; D008136:Longevity; D008297:Male; D057093:Orphan Nuclear Receptors; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D014280:Triglycerides / Q000097:blood
D001057:Apolipoproteins E; D004268:DNA-Binding Proteins; D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D014280:Triglycerides