Multifactorial Determinants of Childhood Hearing Loss in Rural Alaska

阿拉斯加农村地区儿童听力损失的多因素决定因素

基本信息

批准号：
10203917
负责人：
Susan Davis Emmett
金额：
$ 7.16万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-01 至 2022-05-14
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10203917
关键词：
Achievement Acute Address Adoption Affect Age Alaska Alaska Native Arctic Regions Automobile Driving Biological Markers Birth Carnitine Palmitoyltransferase I Child Child Health Childhood Chronic Cohort Studies Communities Crowding DNA Data Diet Dietary Practices Disease Economics Employment Employment Opportunities Enrollment Environmental Risk Factor Enzymes Epidemiology Exposure to Food Frequencies Functional disorder Funding Future Genes Genetic Health Hearing High Prevalence Home Household Indoor Air Quality Infant Infant Mortality Infection International Intervention Inupiat Language Development Lead Life Link Measures Metabolism Mitochondria Mothers N-3 polyunsaturated fatty acid National Institute of Child Health and Human Development Native-Born Neonatal Screening Nutritional Nutritional status Omega-3 Fatty Acids Otitis Media Outcome Persons Plumbing Population Pregnant Women Prevalence Prospective cohort study Public Health Recurrence Risk Risk Factors Running Rural Population Schools Single Nucleotide Polymorphism Smoking Speech Development Streptococcus pneumoniae Time Underserved Population Vaccination Variant Water Wood stove Yup&apos ik base childhood hearing loss cohort community based research ear infection early childhood fatty acid metabolism fatty acid oxidation genetic risk factor genetic variant health disparity hearing impairment hearing loss risk improved infection risk middle ear nutrition postnatal prenatal public health relevance recurrent infection respiratory rural Alaska socioeconomics statistics western diet

项目摘要

ABSTRACT Hearing loss in children is one of only a few preventable chronic conditions that has lifelong consequences, affecting early language development, school achievement, and future employment. Hearing loss is particularly common in rural Alaska Native children, often related to infection. However, little is known about risk factors driving infection-related hearing loss, and likely genetic, nutritional, and environmental risk factors all contribute. Respiratory illness in Alaska Native children, which often leads to recurrent ear infections, has been associated with the “CPT1A arctic variant.” This single nucleotide variant in the carnitine palmitoyltransferase 1A (CPT1A) gene, required for fatty acid metabolism, is the most common form of CPT1A found in the Yup’ik and Inupiaq Alaska Native people. Two copies of the CPT1A arctic variant are associated with increased risk of respiratory illness, ear infections, and infant mortality. These health effects prompted the State of Alaska to begin universal DNA-based newborn screening for the CPT1A arctic variant in 2016. In addition to genetic risk factors for recurrent infection, nutritional influences in Alaska Native people are shifting as Western diets become increasingly common when traditional subsistence foods, rich in omega-3 polyunsaturated fatty acids (n-3 PUFAs), historically predominated. Lastly, environmental disparities are common in rural Alaska Native communities, including lack of running water in 27% of homes, household crowding, and poor indoor air quality due to wood-burning stoves. The objective of this study is to define the link between the CPT1A arctic variant and childhood hearing loss, and to characterize how environmental and nutritional factors modify this effect on hearing. We will leverage a unique NICHD-funded (1R01HD089951-01) prospective cohort study in northern and western Alaska that will begin enrolling expectant Alaska Native mothers in early 2020 and follow children through age two to assess overall health effects of the CPT1A arctic variant. This proposed study will partner with the NICHD cohort to evaluate, for the first time, underlying risk factors for hearing loss using a multilevel approach incorporating genetic, nutritional, and environmental influences. In Aim 1, we will characterize the relationship between the CPT1A arctic variant and hearing loss in Alaska Native children. We hypothesize that two copies of the CPT1A artic variant will increase the risk of infection-related hearing loss by 70%. In Aim 2, we will evaluate the impact of prenatal and postnatal exposure to traditional subsistence foods and environmental risk factors on the risk of hearing loss in Alaska Native children. We hypothesize that decreased exposure to traditional foods, measured with an n-3 PUFA biomarker, will be associated with an estimated 70% increase in risk of infection-related hearing loss, and environmental factors will increase risk of infection-related hearing loss by an estimated 60%. These factors will modify the association between CPT1A and risk of hearing loss. Our results will help to develop future interventions to reduce childhood hearing loss, an important health disparity in Alaska Native children, leading to improved health and socioeconomic outcomes.

抽象的儿童的听力损失是仅有终生后果的少数可预防的慢性疾病之一，影响早期语言发展，学校成就和未来的就业。听力损失尤其是在阿拉斯加农村儿童中常见，通常与感染有关。但是，关于风险因素知之甚少驱动与感染相关的听力损失以及可能的遗传，营养和环境风险因素都有贡献。阿拉斯加本地儿童的呼吸道疾病经常导致耳朵感染，已经相关带有“ CPT1A北极变体”。肉碱棕榈转移酶1A（CPT1A）中的单个核苷酸变体脂肪酸代谢所需的基因是在Yup’ik和Inupiaq中发现的最常见的CPT1a形式阿拉斯加土著人。 CPT1A北极变体的两个副本与呼吸道风险增加有关疾病，耳部感染和婴儿死亡率。这些健康效应促使阿拉斯加国开始普遍基于DNA的新生儿筛查2016年CPT1A北极变体。除了遗传风险因素随着西方饮食的变化，反复感染，阿拉斯加原住民的营养影响正在转移当传统的生存食品中越来越普遍，富含omega-3多不饱和脂肪酸（n-3） pufas），历史上以历史为主导。最后，环境差异在阿拉斯加农村地区很常见社区，包括27％的家庭，家庭拥挤和室内空气质量不足的社区由于燃木炉。这项研究的目的是定义CPT1A北极之间的联系变体和儿童期听力损失，并表征环境和营养因素如何修改这种对听力的影响。我们将利用独特的NICHD资助（1R01HD089951-01）在阿拉斯加北部和西部的队列研究将开始在早期入学的阿拉斯加原住民母亲 2020年，并跟随儿童到二岁，以评估CPT1A北极变体的整体健康影响。这拟议的研究将与NICHD队列合作，首次评估听力的风险因素使用多级方法损失，结合了遗传，营养和环境影响。在AIM 1中，我们将表征阿拉斯加本地儿童的CPT1A北极变体与听力损失之间的关系。我们假设CPT1A辅助变体的两个副本将增加与感染相关的听力损失的风险增长70％。在AIM 2中，我们将评估产前和产后对传统生存的影响食品和环境风险因素是阿拉斯加原住民儿童听力损失的风险。我们假设这一点通过N-3 PUFA生物标志物测量的传统食物的接触降低将与估计与感染相关的听力损失风险增加了70％，环境因素将增加与感染有关的听力损失估计为60％。这些因素将改变CPT1A之间的关联和听力损失的风险。我们的结果将有助于制定未来的干预措施，以减少儿童听力损失，阿拉斯加原住民的重要健康差异，从而改善了健康和社会经济成果。