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Alzheimer's Disease Risk Alleles Profiled in Latino Populations

By Labmedica International staff writers
Posted on 24 Dec 2018
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Image: The Infinium Omni2.5-8 BeadChip offers an optimal and comprehensive set of both common and rare single nucleotide polymorphism (SNP) content (Photo courtesy of Illumina).
Image: The Infinium Omni2.5-8 BeadChip offers an optimal and comprehensive set of both common and rare single nucleotide polymorphism (SNP) content (Photo courtesy of Illumina).
The apolipoprotein E (APOE) gene encodes three common isoforms known as ε2, ε3, and ε4. These are determined by two single nucleotide polymorphisms (SNPs) that result in amino acid substitutions and associated functional changes in the protein.

The APOε4 isoform is associated with increased circulating levels of total cholesterol and low-density lipoprotein (LDL), cardiovascular risk, Alzheimer’s disease (AD), and related dementias (ADRD); whereas APOε2 is associated with cognitive resilience and extended longevity.

A team of scientists collaborating with the University of Texas Health Science Center (Houston, TX, USA) used a custom array to genotype APOE in nearly 10,900 individuals with diverse Latino ancestry from four metropolitan areas in the USA. The genotyped participants included representatives from Central American, Cuban, Dominican, Mexican, Puerto Rican, and South American populations, and had an average age of just over 41 years and slightly more than half of the target population (50.4%) was female. Genome-wide SNP genotyping was performed on the participants using a custom Illumina array consisting of the HumanOmni2.5–8v1–1 array content along with a panel of ∼150,000 investigator-chosen SNPs.

The team found that Dominican, Puerto Rican, and Cuban individuals tended to have higher frequencies of the well known ADRD and cognitive decline risk allele APOε4. That risky APOε4 allele was found at almost 18% frequency in Dominicans, while Cubans and Puerto Ricans carried the allele at intermediate frequency. However, it appeared to be far less common in individual from mainland populations in Mexico, Central America, and South America, which had APOε4 frequencies of around 11%.

Conversely, the team found that the APOε2 allele, which has been proposed as a protective factor against cognitive decline and ADRD, was found at enhanced frequencies in individuals from Caribbean Latino populations, dipping in individuals from Central America, and turning up at the lowest frequencies in the South American and Mexican populations. The APOε3 allele, the most common version of APOE across human populations profiled so far, was found in more than 86% of Mexicans and in almost 74% of Dominicans.

The authors concluded that the APOE allele and genotype frequency distributions in a large and diverse sample of Latinos with well-characterized ancestry background. These data provide valuable information in this understudied ethnic group and provide the basis for future studies of the association of APOE with ADRD in this fast-growing segment of the US population. The study was published on December 13, 2018, in the journal Scientific Reports.

Related Links:
University of Texas Health Science Center


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