背景:载脂蛋白(APOE)ε4被认为是轻度认知障碍(MCI)的独立危险因素。然而,并非每个具有ε4等位基因的人都会发展为MCI,这表明存在其他易感基因。本研究旨在鉴定MCI易感基因,包括BIN1、MC1R、STARD6和PVRL2,在中国汉族老年人中,并验证它们与MCI发病中APOEε4等位基因的关联。
方法:为了确定BIN1的多态性(rs6733839,rs7561528),MC1R(rs2228479),STARD6(rs10164112),和PVRL2(rs6859)发生在携带APOEε4等位基因的老年MCI患者中,我们进行了一项病例对照研究,包括285例MCI患者和326例健康对照.
结果:APOEε4携带者比例的统计学差异显着,和BESCI,ADAS-cog,NC组和MCI组之间存在CNT评分(均P<0.01)。rs10164112T和rs6859A等位基因的频率在后者中明显高于前者(P=0.01;0.029)。然而,两组间BIN1(rs6733839,rs7561528)和MC1R(rs2228479)的等位基因和基因型分布均无明显差异(均P>0.05)。当按APOEε4状态(携带者/非携带者)分层时,四组中BIN1rs7561528、STARD6rs10164112和PVRL2rs6859的基因型频率(NCε4+,NCε4-,MCIε4+,MCIε4-)显着不同。此外,我们的结果表明,老年携带者中MCI与BIN1rs7561528,STARD6rs10164112和PVRL2rs6859之间存在显着相关性(所有P<0.05)。
结论:这表明在汉族中,老年APOEε4携带者的MCI可能与BIN1(rs7561528)有关,STARD6(rs10164112)和PVRL2(rs6859)。rs7561528基因型AA和rs10164112基因型TT可能是老年APOEε4携带者MCI的保护因素。
BACKGROUND: Apolipoprotein (APOE) ε4 is recognized as an independent risk factor for mild cognitive impairment (MCI). However, not everyone with the ε4 allele develops MCI, suggesting that other susceptibility genes exist. This study aimed to identify MCI susceptibility genes, including
BIN1, MC1R, STARD6, and PVRL2, in elderly Han Chinese and to verify their association with APOE ε4 allele in MCI onset.
METHODS: To determine whether polymorphisms in
BIN1 (rs6733839, rs7561528), MC1R (rs2228479), STARD6 (rs10164112), and PVRL2 (rs6859) occurred in elderly MCI patients carrying APOE ε4 allele, we carried out a case-control study including 285 MCI patients and 326 healthy controls.
RESULTS: Statistically significant differences in the proportion of APOE ε4 carriers, and BESCI, ADAS-cog, and CNT scores existed between the NC and MCI groups (all P < 0.01). Frequencies of the rs10164112 T and rs6859 A alleles were significantly higher in the latter than in the former (P = 0.01; 0.029). However, no significant differences in allele and genotype distribution of
BIN1 (rs6733839, rs7561528) and MC1R (rs2228479) existed between samples in our two groups (all P > 0.05). When stratified by APOE ε4 status (carriers/non-carriers), genotype frequencies of
BIN1 rs7561528, STARD6 rs10164112, and PVRL2 rs6859 among the four groups (NCε4+, NCε4-, MCIε4+, MCIε4-) were significantly different. Additionally, our results suggest a significant association between MCI and BIN1 rs7561528, STARD6 rs10164112, and PVRL2 rs6859 (all P<0.05) in elderly carriers.
CONCLUSIONS: This suggests that among the Han Chinese, MCI in elderly APOE ε4 carriers may be related to the
BIN1 (rs7561528), STARD6 (rs10164112) and PVRL2 (rs6859). Genotype AA of rs7561528 and TT of rs10164112 might be protective factors against MCI in elderly APOE ε4 carriers.