APOE Promoter Polymorphism-219T/G is an Effect Modifier of the Influence of APOE ε4 on Alzheimer’s Disease Risk in a Multiracial Sample
| Autor: | Catriona McLean, Alzheimer's Disease Neuroimaging Initative, Ari Chong, Woo Keun Song, Sujin Seo, Pan-Woo Ko, Min Soo Byun, Ji Yeon Chung, Ho-Won Lee, Ryozo Kuwano, Gyungah Jun, Min-Kyung Song, Seong Soo A. An, So-Yoon Won, Sungho Won, Dong Young Lee, Jee Hyang Jeong, Jangho Jeong, Sangmyung Rhee, Kyung Won Park, Ji Won Han, Wooje Lee, Jang Jae Lee, Kyu Yeong Choi, Hoowon Kim, Takeshi Ikeuchi, Congcong Zhu, Ho Jae Lim, John J. Farrell, Byeong C. Kim, Jungsoo Gim, Akinori Miyashita, Young-Min Lee, Jung-Min Ha, I L Han Choo, Richard Mayeux, Eun Hyun Seo, Margaret A. Pericak-Vance, Yu Yong Choi, Seok Cheol Lee, Tamil Iniyan Gunasekaran, Gerard D. Schellenberg, Kathryn L. Lunetta, Sarang Kang, Seong Hye Choi, Seong-Min Choi, Norikazu Hara, Ki Woong Kim, Jonathan L. Haines, SangYun Kim, Kwangsik Nho, Xiaoling Zhang, Kun Ho Lee, Lindsay A. Farrer, Jung Sup Lee |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Apolipoprotein E
medicine.medical_specialty genetic association lcsh:Medicine Single-nucleotide polymorphism Article 03 medical and health sciences 0302 clinical medicine Internal medicine Genotype medicine SNP Allele 10. No inequality Allele frequency 030304 developmental biology Genetic association 0303 health sciences business.industry lcsh:R ethnic variability General Medicine Odds ratio APOE promoter polymorphism Endocrinology business Alzheimer’s disease 030217 neurology & neurosurgery brain atrophy |
| Zdroj: | Journal of Clinical Medicine Volume 8 Issue 8 Journal of Clinical Medicine, Vol 8, Iss 8, p 1236 (2019) |
| ISSN: | 2077-0383 |
| DOI: | 10.3390/jcm8081236 |
| Popis: | Variants in the APOE gene region may explain ethnic differences in the association of Alzheimer’s disease (AD) with ε4. Ethnic differences in allele frequencies for three APOE region SNPs (single nucleotide polymorphisms) were identified and tested for association in 19,398 East Asians (EastA), including Koreans and Japanese, 15,836 European ancestry (EuroA) individuals, and 4985 African Americans, and with brain imaging measures of cortical atrophy in sub-samples of Koreans and EuroAs. Among ε4/ε4 individuals, AD risk increased substantially in a dose-dependent manner with the number of APOE promoter SNP rs405509 T alleles in EastAs (TT: OR (odds ratio) = 27.02, p = 8.80 × 10−94 GT: OR = 15.87, p = 2.62 × 10−9) and EuroAs (TT: OR = 18.13, p = 2.69 × 10−108 GT: OR = 12.63, p = 3.44 × 10−64), and rs405509-T homozygotes had a younger onset and more severe cortical atrophy than those with G-allele. Functional experiments using APOE promoter fragments demonstrated that TT lowered APOE expression in human brain and serum. The modifying effect of rs405509 genotype explained much of the ethnic variability in the AD/ε4 association, and increasing APOE expression might lower AD risk among ε4 homozygotes. |
| Databáze: | OpenAIRE |
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