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.
Conclusion: 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.
Keywords: mild cognitive impairment, BIN1 , MC1R , STARD6 , PVRL2 , APOE , polymorphism, association analysis