Bathum Lise, Christiansen Lene, Tan Qihua, Vaupel James, Jeune Bernard, Christensen Kaare
Department of Clinical Biochemistry, Odense University Hospital, Odense, Denmark.
Eur J Hum Genet. 2005 Oct;13(10):1154-8. doi: 10.1038/sj.ejhg.5201468.
Previous studies have reported two SNPs and a haplotype marker within the Microsomal Transfer Protein gene associated with extreme longevity. Here, we test this finding in a longitudinal study of nonagenarians and in an association study. Participants in the Danish 1905 cohort study (1651 participants aged 92-93 years) were genotyped for the two SNPs (rs2866164 and Q95H) in the Microsomal Transfer Protein gene recently reported to be associated with longevity. The 1905 Cohort has been followed for 6.5 years, during which period 83% of the cohort has died. Furthermore, a group of 575 middle-aged Danish twins (mean age 53.7 years) were tested as a younger control group. The risk haplotype had no significant survival disadvantage (P-values: 0.56, 0.31 and 0.97 in the total population of nonagenarians, males and females, respectively) after 6.5 years of follow-up. The distributions of the suggested risk alleles (rs2866164-G and Q95) and the resulting haplotypes are very similar and not statistically different between the two age cohorts. The frequency for rs2866164-G is in the middle-aged compared to the nonagenarians 25.4 and 23.6% in males and 23.0 and 26.1% in females. The frequency for the risk haplotype is in the middle-aged compared to the nonagenarians 22.7 and 19.2% in males and 18.1 and 21.8% in females. In conclusion, our longitudinal study of survival in the 10th decade of life and an association study in a genetically homogeneous population provided no support for an association between the Microsomal Transfer Protein gene and extreme longevity.
以往研究报告称，微粒体转移蛋白基因内的两个单核苷酸多态性（SNP）及一个单倍型标记与极端长寿相关。在此，我们在一项针对九旬老人的纵向研究及一项关联研究中对这一发现进行验证。丹麦1905队列研究（1651名年龄在92 - 93岁的参与者）的参与者针对微粒体转移蛋白基因中最近报告的与长寿相关的两个SNP（rs2866164和Q95H）进行了基因分型。对1905队列进行了6.5年的随访，在此期间该队列83%的人已经死亡。此外，一组575名中年丹麦双胞胎（平均年龄53.7岁）作为较年轻的对照组接受检测。经过6.5年的随访，风险单倍型并无显著的生存劣势（在九旬老人总体人群、男性和女性中的P值分别为0.56、0.31和0.97）。两个年龄队列之间，所提示的风险等位基因（rs2866164 - G和Q95）及由此产生的单倍型的分布非常相似，且无统计学差异。rs2866164 - G在中年男性中的频率为25.4%，九旬老人中为23.6%；中年女性中为23.0%，九旬老人中为26.1%。风险单倍型在中年男性中的频率为22.7%，九旬老人中为19.2%；中年女性中为18.1%，九旬老人中为21.8%。总之，我们对生命第十个十年的生存情况进行的纵向研究以及在基因同质人群中开展的关联研究，均未支持微粒体转移蛋白基因与极端长寿之间存在关联。
