Chromosome 4q25, microsomal transfer protein gene, and human longevity: novel data and a meta-analysis of association studies.
Recently, chromosome 4q25 was linked to exceptional human longevity, and a haplotype of the positional candidate microsomal transfer protein (MTP) gene was associated to the phenotype in U.S. Caucasians. We investigated whether linkage to 4q25 could be detected in 164 nonagenarian sibships of the Leiden Longevity Study. Additionally, we compared the MTP -493G/T and Q95H allele and haplotype frequencies in the Leiden Longevity Study (379 nonagenarians, 525 of their offspring, and 251 partners of their offspring) and in the Leiden 85-Plus Study (655 octogenarians and 244 young controls). The latter study population was followed for at least 7 years, providing the opportunity to perform also prospective analyses using the longitudinal data. We found neither evidence for linkage at 4q25 nor association of the MTP locus with longevity in nonagenarian individuals. Meta-analyses of all previous studies implied that the association in U.S. Caucasians may have its source in admixture of the U.S. control population rather than in the genetic effect of the locus on exceptional longevity.
Beekman
Marian
M
Section of Molecular Epidemiology, Department of General Internal Medicine, Leiden University Medical Center, P.O. Box 9503, 2300 RA Leiden, The Netherlands. M.Beekman@LUMC.nl
Blauw
Gerard Jan
GJ
Houwing-Duistermaat
Jeanine J
JJ
Brandt
Bernd W
BW
Westendorp
Rudi G J
RG
Slagboom
P Eline
PE
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002352:Carrier Proteins / Q000235:genetics*; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D008040:Genetic Linkage / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008136:Longevity / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D015996:Survival Rate
D002352:Carrier Proteins; C106092:microsomal triglyceride transfer protein