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：
10056632
负责人：
Susan Davis Emmett
金额：
$ 21.61万
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 2022-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10056632
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 environment 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 participatory 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.

抽象的儿童听力损失是少数可预防且会造成终生后果的慢性疾病之一，听力损失尤其影响早期语言发展、学业成绩和未来就业。常见于阿拉斯加农村土著儿童，通常与感染有关。但是，人们对危险因素知之甚少。导致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会造成影响。阿拉斯加原住民儿童的呼吸道疾病经常导致反复耳部感染，这与与“CPT1A 北极变体”。肉毒碱棕榈酰转移酶 1A (CPT1A) 中的这种单核苷酸变体脂肪酸代谢所需的基因是在尤皮克人和因努皮克人中发现的最常见的 CPT1A 形式阿拉斯加原住民中 CPT1A 北极变体的两个拷贝与呼吸道疾病风险增加有关。疾病、耳部感染和婴儿死亡率这些健康影响促使阿拉斯加州开始普及。 2016 年基于 DNA 的新生儿筛查 CPT1A 北极变异。除了遗传风险因素随着西方饮食变得越来越流行，阿拉斯加原住民的反复感染和营养影响正在发生变化富含 omega-3 多不饱和脂肪酸（n-3 最后，环境差异在阿拉斯加原住民的农村地区很常见。社区，包括 27% 的家庭缺乏自来水、家庭拥挤以及室内空气质量差这项研究的目的是确定 CPT1A 北极地区之间的联系。变异和儿童听力损失，并描述环境和营养因素如何影响听力损失我们将利用 NICHD 资助的独特的 (1R01HD089951-01) 前瞻性技术来改变这种影响。阿拉斯加北部和西部的队列研究将于年初开始招募阿拉斯加原住民准妈妈 2020 年，跟踪儿童至两岁，评估 CPT1A 北极变种的整体健康影响。拟议的研究将与 NICHD 队列合作，首次评估听力的潜在风险因素在目标 1 中，我们采用结合遗传、营养和环境影响的多层次方法来减少损失。将描述 CPT1A 北极变异与阿拉斯加原住民儿童听力损失之间的关系。我们发现两个 CPT1A 北极变体副本会增加感染相关听力损失的风险在目标 2 中，我们将评估产前和产后接触传统生活方式的影响。食品和环境风险因素对阿拉斯加原住民儿童听力损失风险的影响。使用 n-3 PUFA 生物标志物测量的传统食品暴露量将与据估计，感染相关听力损失的风险增加 70%，而环境因素会增加听力损失的风险估计 60% 的感染相关听力损失这些因素将改变 CPT1A 之间的关联。我们的研究结果将有助于制定未来的干预措施，以减少儿童听力损失，阿拉斯加原住民儿童的健康状况存在重大差异，从而改善了健康和社会经济成果。