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Mitochondrial DNA oxidative mutations are elevated in Mexican American women potentially implicating Alzheimer's disease.

ABSTRACT: Mexican Americans (MAs) are the fastest-growing Hispanic population segment in the US; as this population increases in age, so will the societal burden of age-related diseases such as Alzheimer's disease (AD). Mitochondrial DNA (mtDNA) damage may be implicated in MA AD risk since metabolic comorbidities are more prevalent in this group. Oxidative damage to guanosine (8oxoG) is one of the most prevalent DNA lesions and a putative indicator of mitochondrial dysfunction. Testing blood samples from participants of the Texas Alzheimer's Research and Care Consortium, we found mtDNA 8oxoG mutational load to be significantly higher in MAs compared to non-Hispanic whites and that MA females are differentially affected. Furthermore, we identified specific mtDNA haplotypes that confer increased risk for oxidative damage and suggestive evidence that cognitive function may be related to 8oxoG burden. Our understanding of these phenomena will elucidate population- and sex-specific mechanisms of AD pathogenesis, informing the development of more precise interventions and therapeutic approaches for MAs with AD in the future.

SUBMITTER: Reid DM

PROVIDER: S-EPMC9158774 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Mitochondrial DNA oxidative mutations are elevated in Mexican American women potentially implicating Alzheimer's disease.

Reid Danielle Marie DM Barber Robert C RC Thorpe Roland J RJ Sun Jie J Zhou Zhengyang Z Phillips Nicole R NR

npj aging 20220404 1

Mexican Americans (MAs) are the fastest-growing Hispanic population segment in the US; as this population increases in age, so will the societal burden of age-related diseases such as Alzheimer's disease (AD). Mitochondrial DNA (mtDNA) damage may be implicated in MA AD risk since metabolic comorbidities are more prevalent in this group. Oxidative damage to guanosine (8oxoG) is one of the most prevalent DNA lesions and a putative indicator of mitochondrial dysfunction. Testing blood samples from ...[more]

PMID: 35927256

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Project description:BackgroundThe enrollment into clinical trials of persons at risk for autosomal dominant Alzheimer's disease (ADAD) in whom the onset of disease can be accurately predicted facilitates the interpretation of outcomes (e.g., biomarkers, treatment efficacy). Attitudes toward involvement in such studies are biased by intrinsic cultural and social characteristics. Our objective was to study how demographic factors such as country of residence, age, sex, schooling, parenthood, and urbanization affect attitudes towards participation in hypothetical clinical trials in Mexican families at risk for ADAD living either in Mexico or in the United States.MethodsParticipants were 74 members of different families known to harbor an ADAD mutation living in Mexico (n = 50) or in the United States (n = 24). Participants were asked, in a written questionnaire, their interest in participating in four hypothetical clinical trial scenarios of increasing perceived invasiveness. The questionnaire then asked about their willingness should there be a 50% chance of being assigned to a placebo group. The influences of demographic variables on decisions were performed using Wilcoxon rank-sum for continuous variables and Fisher's exact test for categorical variables.ResultsParticipants who live in Mexico, who have or plan to have children, who do not attend or do not plan to attend school, and who live in rural areas gave more positive responses regarding their willingness to participate compared to those living in the U.S. The 50% chance of being in a placebo group increased the willingness to participate for family members living in Mexico. The main reason for participation was to help future generations, while the main reasons for refusal were not wanting to undergo genetic testing and consideration of adverse effects.ConclusionsWe found a higher level of willingness to participate in clinical trials among persons living in rural Mexico and our data suggest that altruism towards future generations is a major motivation, though this was balanced against concerns regarding side effects. Our results emphasize the importance of sharing information and assessing its understanding in potential participants with diverse backgrounds in the nature of ADAD and regarding the design of clinical trials prior to their enrollment in such studies.

Dataset Information

Mitochondrial DNA oxidative mutations are elevated in Mexican American women potentially implicating Alzheimer's disease.

Publications

Mitochondrial DNA oxidative mutations are elevated in Mexican American women potentially implicating Alzheimer's disease.

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