北京大學(xué)分子醫(yī)學(xué)研究所人類群體遺傳研究室田小利教授與國家發(fā)展研究院中國經(jīng)濟(jì)研究中心曾毅教授聯(lián)合研究組發(fā)現(xiàn)FOXO1A和FOXO3A基因與長壽相關(guān),。他們的研究表明FOXO1A與我國女性的長壽相關(guān),，而FOXO3A基因則沒有性別差異,。該研究結(jié)果發(fā)表于經(jīng)典遺傳學(xué)雜志《人類分子遺傳學(xué)》（Human Molecular Genetics）。
健康長壽是每一個人的夢想,，但影響健康長壽的因素很多，包括性別,、遺傳,、生活習(xí)慣和生活環(huán)境及其相互作用等。在年齡大于85歲的人群中女性約占70-85%,，而男性僅為15-30%,。盡管女性的長壽優(yōu)勢可見于已經(jīng)報道的所有人種，但原因尚不明確,。田小利教授研究組首次發(fā)現(xiàn)FOXO1A基因與女性的長壽相關(guān),，將有助于解釋女性長壽之謎。FOXO3A基因曾報道與其他的人群（如日本人,、德國人和意大利人等）的長壽相關(guān),。中國人FOXO3A基因的長壽位點(diǎn)與其他人群的長壽位點(diǎn)共存于一個單倍型中。
FOXO1A和FOXO3A是胰島素或胰島素樣生長因子介導(dǎo)的下游信號通路分子,與細(xì)胞周期,、生長,、凋亡以及血管新生等有密切關(guān)系。在代謝方面,，它們的主要功能是平衡胰島素的敏感性和抗性,，參與癌癥、自身免疫病以及心血管疾病如缺血性心臟病,、心肌肥大等,。田小利教授等推測FOXO3A可能通過調(diào)節(jié)胰島素抗性和長壽相關(guān)，而FOXO1A則除調(diào)節(jié)胰島素抗性外,，可能還通過與女性生殖系統(tǒng)相互作用而影響人的壽命,。
田小利教授研究組主要致力于尋找心血管疾病相關(guān)基因，并研究它們在心血管系統(tǒng)的發(fā)育,、疾病及衰老過程中的作用機(jī)制,。比較分析“患病與健康人群”和“長壽與普通人群”的遺傳位點(diǎn)的異同，尋找心血管疾病致病和保護(hù)基因是重要的研究手段,。在這個研究中,，他們比較分析了1000個百歲老人和1000個年輕人的FOXO1A及FOXO3A基因型，得出這兩個基因與長壽相關(guān)的結(jié)論。其中1000個百歲老人基因來自曾毅教授課題組1998年收集的4000份高齡老人血樣,。參與此研究的還有重慶第三軍醫(yī)大學(xué)祝之明教授,、華西醫(yī)科大學(xué)莫顯明教授以及寧波市第一醫(yī)院陳曉敏教授等。
目前北京大學(xué)健康長壽跨學(xué)科研究團(tuán)隊(duì)正在研究社會,、行為,、環(huán)境與FOXO1A及FOXO3A基因的相互作用，期望發(fā)現(xiàn)遺傳,、社會,、行為、環(huán)境因素等相互作用影響老年人的健康與長壽的可能機(jī)制,。（生物谷Bioon.com）
生物谷推薦原始出處：
Human Molecular Genetics, doi:10.1093/hmg/ddp459
Genetic association of FOXO1A and FOXO3A with longevity trait in Han Chinese populations
Yang Li1,, Wen-Jing Wang1,, Huiqing Cao1,, Jiehua Lu8, Chong Wu1, Fang-Yuan Hu1, Jian Guo1, Ling Zhao1, Fan Yang1, Yi-Xin Zhang1, Wei Li1, Gu-Yan Zheng1, Hanbin Cui4, Xiaomin Chen5, Zhiming Zhu6, Hongbo He6, Birong Dong7, Xianming Mo7, Yi Zeng2,3,* and Xiao-Li Tian1,*
1 Department of Human Population Genetics, Institute of Molecular Medicine and 2 China Center for Economic Research, National School of Development, Peking University, 5 Yiheyuan Rd., Beijing 100871, China 3 Center for Study of Aging and Human Development, Medical School of Duke University, BUSSE Building, Duke University, Durham, NC 27710, USA, 4 Key Laboratory of Ningbo First Hospital and 5 Cardiovascular Center of Ningbo First Hospital, Ningbo University, Liuting Str. 59 Ningbo 315010, 6 Center for Hypertension and Metabolic Diseases, Department of Hypertension and Endocrinology, Daping Hospital, Third Military Medical University, Chongqing Institute of Hypertension, Chongqing 400042, and 7 Department of Geriatrics, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China 8 Department of Sociology and Center for Healthy Aging and Family Studies, Peking University
FOXO1A and FOXO3A are two members of the FoxO family. FOXO3A has recently been linked to human longevity in Japanese, German, and Italian populations. Here we tested the genetic contribution of FOXO1A and FOXO3A to the longevity phenotype in Han Chinese population. Six tagging SNPs from FOXO1A and FOXO3A were selected and genotyped in 1817 centenarians and younger individuals. Two SNPs of FOXO1A were found to be associated with longevity in women (P = 0.01-0.005), whereas all three SNPs of FOXO3A were associated with longevity in both genders (P = 0.005-0.001). One SNP from FOXO1A was found not to be associated with longevity. In haplotype association tests, the OR (CI95%) for haplotypes TTG and CCG of FOXO1A in association with female longevity were 0.72 (0.58-0.90) and 1.38 (1.08-1.76), P = 0.0033 and 0.0063, respectively. The haplotypes of FOXO3A were associated with longevity in men (GTC: OR (CI95%)=0.67 (0.51-0.86), P = 0.0014; CGT: OR (CI95%)=1.48 (1.12-1.94), P = 0.0035) and in women (GTC: OR (CI95%)=0.75 (0.60-0.94), P = 0.0094; CGT: OR (CI95%)=1.47 (1.16-1.86), P = 0.0009). The haplotype association tests were validated by permutation analysis. The association of FOXO1A with female longevity was replicated in 700 centenarians and younger individuals that were sampled geographically different from the original population. Thus, we demonstrate that, unlike FOXO3A, FOXO1A is more closely associated with human female longevity, suggesting that the genetic contribution to longevity trait may be affected by genders.
