Rontu Riikka, Ojala Petri, Hervonen Antti, Goebeler Sirkka, Karhunen Pekka J, Nikkilä Matti, Kunnas Tarja, Jylhä Marja, Eklund Carita, Hurme Mikko, Lehtimäki Terho
Laboratory of Atherosclerosis Genetics, Tampere University Hospital, Centre for Laboratory Medicine and Department of Clinical Chemistry, University of Tampere, Medical School, Finland.
Clin Endocrinol (Oxf). 2006 Mar;64(3):265-70. doi: 10.1111/j.1365-2265.2006.02455.x.
Apolipoprotein E (APOE) genotype is a regulator of hepatic lipoprotein metabolisms and has been linked with longevity. The relationship between APOE genotype and plasma C-reactive protein (CRP), which is produced by the liver during inflammation, has not been studied in nonagenarians. The aim of the present study was to establish whether APOE genotype is related to plasma concentrations of CRP and lipids, or longevity among nonagenarians.
This cross-sectional study consisted of 291 Finnish nonagenarians and three previously described and genotyped control populations from the same area (i.e. newborns, 40-year-olds, and 70-year-olds).
In all nonagenarians and especially in women (P= 0.038), CRP level decreased linearly in the genotype order of epsilon2/2, epsilon2/3, epsilon3/3, epsilon2/4, epsilon3/4 and epsilon4/4. Total (P= 0.009) and low-density lipoprotein (LDL) cholesterol (P = 0.076) levels, in turn, were increased in the epsilon4 allele carriers. In newborns, the epsilon4 frequency was 0.192, in 40-year-olds 0.181, in 70-year-olds 0.179 and in nonagenarians 0.095 (P < 0.0001). The decrease in the epsilon4 allele frequency in the elderly was more clearly seen in women than in men.
APOEepsilon4 allele seems to be associated with decreased inflammatory response as measured by CRP among nonagenarians. This finding may partly explain why some epsilon4 allele carriers can reach very old age despite increased risk of hypercholesterolaemia.
载脂蛋白E(APOE)基因型是肝脏脂蛋白代谢的调节因子,与长寿有关。百岁老人中尚未研究APOE基因型与炎症期间由肝脏产生的血浆C反应蛋白(CRP)之间的关系。本研究的目的是确定APOE基因型是否与百岁老人的血浆CRP和脂质浓度或长寿有关。
这项横断面研究由291名芬兰百岁老人和来自同一地区的三个先前描述并进行基因分型的对照人群(即新生儿、40岁人群和70岁人群)组成。
在所有百岁老人中,尤其是女性(P = 0.038),CRP水平按ε2/2、ε2/3、ε3/3、ε2/4、ε3/4和ε4/4的基因型顺序呈线性下降。而ε4等位基因携带者的总胆固醇(P = 0.009)和低密度脂蛋白(LDL)胆固醇水平(P = 0.076)升高。新生儿中ε4频率为0.192,40岁人群中为0.181,70岁人群中为0.179,百岁老人中为0.095(P < 0.0001)。老年人中ε4等位基因频率的下降在女性中比在男性中更明显。
在百岁老人中,APOEε4等位基因似乎与CRP测量的炎症反应降低有关。这一发现可能部分解释了为什么一些ε4等位基因携带者尽管患高胆固醇血症的风险增加,但仍能活到很高的年龄。