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The impact of enculturation on the epigenetic relationship between chronic stress and hypertension in Yup'ik Alaska Native people

Award Number: R01MD014618
ORGANIZATION: NATIONAL CENTER ON MINORITY HEALTH AND HEALTH DISPARITIES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary The objective of the proposed research is to identify molecular mechanisms linking the protective role of culture to blood pressure regulation, a major risk factor for stroke in Yup'ik Alaska Native people. The prevalence of stroke is higher among American Indian and Alaska Native (AIAN) populations than in any other U.S. racial/ethnic group. Chronic psychological stress increases the risk for hypertension, and is the most frequently cited stroke risk factor in AIAN populations. The prevalence of stroke has increased over the past 25 years, and is likely brought on by chronic stressors including historical trauma, cultural change and adverse socioeconomic conditions which, in turn, increases the likelihood of unhealthy behavioral coping responses (e.g., smoking, reduced exercise, poor sleep and overeating). However, our previous research has shown that both strong adherence to Yup'ik cultural traditions (enculturation) and dual adherence to Yup'ik and White culture (biculturalism) are associated with healthier blood pressure when compared to Yup'ik individuals adhering to a more Western lifestyle (acculturation). No previous research has identified the molecular events underlying the basis for the protective effects of enculturation/biculturalism-induced resilience (EBIR) on risk for hypertension, representing a critical barrier to the development of culturally effective interventions aimed at promoting health. The proposed research examines the role of EBIR at each step of the stress-disease cascade – a model based on extensive research linking chronic stressful events to biological mechanisms and diseases such as hypertension. We hypothesize that EBIR blocks or buffers adverse individual and environmental stressors resulting in reduced metabolic dysfunction and inflammation, inhibition of epigenetic dysregulation, and maintenance of leukocyte telomere length, all or some of which lead to healthy blood pressure. We test these hypotheses by addressing the following Specific Aims (SAs): SA1 - Conduct latent class analysis using self- reported data about enculturation, biculturalism, and chronic stress from 800 Yup'ik participants to form classes based on their degree of EBIR/stress (SA1a), followed by evaluating the relationship between EBIR/stress latent classes and maladaptive health-related behaviors as well as between blood pressure, the main study outcome measure (SA1b); SA2 - Evaluate the association between EBIR/stress latent classes with metabolic dysfunction (salivary cortisol, fasting plasma glucose and HbA1c levels, and lipid levels), mitochondrial allostatic load, and chronic low-grade inflammation; and SA3 - Determine the impact of EBIR/stress latent classes on epigenome- wide DNA methylation and downstream changes in gene expression (SA3a) as well as quantify the association between methylation sites and blood pressure (SA3b), and test whether differential methylation mediates the association between EBIR/stress latent classes and blood pressure (SA3c). We will also evaluate leukocyte telomere length among individuals in each of the EBIR/stress latent classes (SA3d) in order to determine whether EBIR reduces the impact of chronic stress on premature telomere shortening, an indicator of biological aging.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $73,953 )
2024	2024	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Minority Health and Health Disparities Research	000	4	12/8/2023	NON-COMPETING CONTINUATION	$599,722
2024	2024	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Minority Health and Health Disparities Research	001	4	12/20/2023	NON-COMPETING CONTINUATION	-$525,769
														Subtotal = $73,953

Issue Date FY: 2023 ( Subtotal = $385,622 )
2023	2023	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Minority Health and Health Disparities Research	001	3	2/6/2023	NON-COMPETING CONTINUATION	$68,563
2023	2023	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Minority Health and Health Disparities Research	000	3	12/11/2022	NON-COMPETING CONTINUATION	$317,059
														Subtotal = $385,622

Issue Date FY: 2022 ( Subtotal = $695,639 )
2022	2022	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Minority Health and Health Disparities Research	002	2	4/27/2022	NON-COMPETING CONTINUATION	$69,565
2022	2022	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Minority Health and Health Disparities Research	001	2	12/20/2021	NON-COMPETING CONTINUATION	$626,074
2022	2021	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Minority Health and Health Disparities Research	000	1	12/2/2021	NEW	$0
														Subtotal = $695,639

Issue Date FY: 2021 ( Subtotal = $742,410 )
2021	2021	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Minority Health and Health Disparities Research	001	1	7/21/2021	NEW	$82,490
2021	2021	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Minority Health and Health Disparities Research	000	1	2/2/2021	NEW	$659,920
														Subtotal = $742,410

Grand Total All Awards = $1,897,624

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The impact of enculturation on the epigenetic relationship between chronic stress and hypertension in Yup'ik Alaska Native people

Award Number: R01MD014618

ORGANIZATION: NATIONAL CENTER ON MINORITY HEALTH AND HEALTH DISPARITIES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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