Beekman Marian, Blauw Gerard Jan, Houwing-Duistermaat Jeanine J, Brandt Bernd W, Westendorp Rudi G J, Slagboom P Eline
Section of Molecular Epidemiology, Department of General Internal Medicine, Leiden University Medical Center, P.O. Box 9503, 2300 RA Leiden, The Netherlands.
J Gerontol A Biol Sci Med Sci. 2006 Apr;61(4):355-62. doi: 10.1093/gerona/61.4.355.
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.
最近，4号染色体q25区域与人类的超长寿命相关，并且一个位于该位置的候选基因——微粒体转移蛋白（MTP）基因的单倍型，在美国白种人中与这一表型相关。我们对莱顿长寿研究中的164个百岁老人同胞对进行研究，检测是否存在与4q25区域的连锁。此外，我们比较了莱顿长寿研究（379名百岁老人、525名他们的后代以及251名他们后代的配偶）和莱顿85岁及以上老人研究（655名八旬老人和244名年轻对照）中MTP基因-493G/T和Q95H等位基因及单倍型频率。后一个研究群体至少随访了7年，这为利用纵向数据进行前瞻性分析提供了机会。我们既没有发现4q25区域存在连锁的证据，也没有发现MTP基因座与百岁老人的长寿相关。对之前所有研究的荟萃分析表明，在美国白种人中发现的这种关联可能源于美国对照人群的混杂因素，而非该基因座对超长寿命的遗传效应。
