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APOE and APOC1 promoter polymorphisms and the risk of Alzheimer disease in African American and Caribbean Hispanic individuals.
Arch Neurol. 2004 Sep; 61(9):1434-9.AN

Abstract

BACKGROUND

The APOE epsilon4 allele is a genetic risk factor for Alzheimer disease (AD), though the strength of the association varies by ethnic group. Polymorphisms in regulatory sequences of APOE have also been related to AD, but the effects are inconsistent across studies.

METHODS

We examined the association between AD and variants in 3 APOE promoters and in the promoter of the adjacent APOC1 gene in African American and Caribbean Hispanic individuals. Polymorphisms tested were the -491A/T, -427T/C, and -219G/T (Th1/E47cs) in the APOE promoter and the HpaI variant in the APOC1 promoter. Using standard research criteria for AD, overall odds ratios were computed and repeated stratified by presence or absence of APOE epsilon4.

RESULTS

The APOC1 HpaI+ variant was associated with AD in Caribbean Hispanic individuals, but strong linkage disequilibrium with the APOE epsilon4 allele indicated that this was not an independent effect. No promoter variant in APOE or APOC1 was associated with AD before or after adjusting for age, education, sex, and multiple comparisons. Estimated haplotypes including -219G/T, APOE, and APOC1 differed significantly in Caribbean Hispanic patients and controls but not in African American participants. This effect was primarily owing to the -219G/T-APOE haplotype, but we did not detect significant allele-specific differences in promoter activity comparing reporter constructs containing the APOE -219G and -219 T alleles.

CONCLUSION

These findings exclude a strong or independent influence of APOE or APOC1 promoter polymorphisms on the variation in APOE-related risk of AD in African American and Caribbean Hispanic individuals.

Authors+Show Affiliations

Department of Pathology, Division of Neuropathology, Columbia University College of Physicians and Surgeons, 630 West 168th Street, New York, NY 10032, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15364690

Citation

Tycko, Benjamin, et al. "APOE and APOC1 Promoter Polymorphisms and the Risk of Alzheimer Disease in African American and Caribbean Hispanic Individuals." Archives of Neurology, vol. 61, no. 9, 2004, pp. 1434-9.
Tycko B, Lee JH, Ciappa A, et al. APOE and APOC1 promoter polymorphisms and the risk of Alzheimer disease in African American and Caribbean Hispanic individuals. Arch Neurol. 2004;61(9):1434-9.
Tycko, B., Lee, J. H., Ciappa, A., Saxena, A., Li, C. M., Feng, L., Arriaga, A., Stern, Y., Lantigua, R., Shachter, N., & Mayeux, R. (2004). APOE and APOC1 promoter polymorphisms and the risk of Alzheimer disease in African American and Caribbean Hispanic individuals. Archives of Neurology, 61(9), 1434-9.
Tycko B, et al. APOE and APOC1 Promoter Polymorphisms and the Risk of Alzheimer Disease in African American and Caribbean Hispanic Individuals. Arch Neurol. 2004;61(9):1434-9. PubMed PMID: 15364690.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - APOE and APOC1 promoter polymorphisms and the risk of Alzheimer disease in African American and Caribbean Hispanic individuals. AU - Tycko,Benjamin, AU - Lee,Joseph H, AU - Ciappa,Alejandra, AU - Saxena,Anjana, AU - Li,Chi-Ming, AU - Feng,Lin, AU - Arriaga,Alex, AU - Stern,Yaakov, AU - Lantigua,Rafael, AU - Shachter,Neil, AU - Mayeux,Richard, PY - 2004/9/15/pubmed PY - 2004/10/8/medline PY - 2004/9/15/entrez SP - 1434 EP - 9 JF - Archives of neurology JO - Arch. Neurol. VL - 61 IS - 9 N2 - BACKGROUND: The APOE epsilon4 allele is a genetic risk factor for Alzheimer disease (AD), though the strength of the association varies by ethnic group. Polymorphisms in regulatory sequences of APOE have also been related to AD, but the effects are inconsistent across studies. METHODS: We examined the association between AD and variants in 3 APOE promoters and in the promoter of the adjacent APOC1 gene in African American and Caribbean Hispanic individuals. Polymorphisms tested were the -491A/T, -427T/C, and -219G/T (Th1/E47cs) in the APOE promoter and the HpaI variant in the APOC1 promoter. Using standard research criteria for AD, overall odds ratios were computed and repeated stratified by presence or absence of APOE epsilon4. RESULTS: The APOC1 HpaI+ variant was associated with AD in Caribbean Hispanic individuals, but strong linkage disequilibrium with the APOE epsilon4 allele indicated that this was not an independent effect. No promoter variant in APOE or APOC1 was associated with AD before or after adjusting for age, education, sex, and multiple comparisons. Estimated haplotypes including -219G/T, APOE, and APOC1 differed significantly in Caribbean Hispanic patients and controls but not in African American participants. This effect was primarily owing to the -219G/T-APOE haplotype, but we did not detect significant allele-specific differences in promoter activity comparing reporter constructs containing the APOE -219G and -219 T alleles. CONCLUSION: These findings exclude a strong or independent influence of APOE or APOC1 promoter polymorphisms on the variation in APOE-related risk of AD in African American and Caribbean Hispanic individuals. SN - 0003-9942 UR - https://www.unboundmedicine.com/medline/citation/15364690/APOE_and_APOC1_promoter_polymorphisms_and_the_risk_of_Alzheimer_disease_in_African_American_and_Caribbean_Hispanic_individuals_ L2 - https://jamanetwork.com/journals/jamaneurology/fullarticle/10.1001/archneur.61.9.1434 DB - PRIME DP - Unbound Medicine ER -