GENETIC EPIDEMIOLOGY OF RESPIRATORY DISTRESS SYNDROME

呼吸窘迫综合征的遗传流行病学

• 批准号: 8516075
• 负责人: Michael William Kuzniewicz
• 金额: $ 12.99万
• 依托单位: KAISER FOUNDATION RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8516075
• 关键词: ATP-Binding Cassette Transporters; Acute; Address; Affect; Binding; Birth; California; Caring; Cessation of life; Chronic; Clinic; Clinical; Code; Complex; Computerized Medical Record; Development; Disease; Dizygotic Twins; Electronics; Environmental air flow; Epidemiologic Studies; Ethnic Origin; Etiology; Family; Functional disorder; Gender; Genes; Genetic; Genetic Code; Genetic Variation; Genotype; Gestational Age; Goals; Health Services; Heterogeneity; Homeostasis; Hospital Costs; Hospitals; Incidence; Infant; Infection; Information Systems; Inpatients; Laboratories; Lead; Length of Stay; Linear Regressions; Logistic Regressions; Lung; Managed Care; Measures; Medical; Medical Records; Metabolic Pathway; Methods; Morbidity - disease rate; Mutation; Outcome; Outpatients; Oxygen; Physicians; Population; Predisposition; Premature Infant; Prevention strategy; Production; Pulmonary Surfactant-Associated Protein A; Pulmonary Surfactant-Associated Protein B; Pulmonary Surfactant-Associated Protein C; Pulmonary Surfactants; Race; Radiology Specialty; Records; Research Personnel; Risk; Risk Factors; Severities; Single Nucleotide Polymorphism; Techniques; Test Result; Testing; Twin Studies; United States; Variant; base; career; case control; clinical epidemiology; clinical risk; cohort; design; developmental genetics; gene environment interaction; genetic epidemiology; genetic variant; improved; maternal diabetes; member; mortality; neonate; premature; programs; respiratory distress syndrome; surfactant; treatment strategy

The candidate's long-term career goal is to become an independent researcher who will integrate methods in genetic epidemiology with those used in health services and clinical epidemiology to improve the care of neonates. Respiratory Distress Syndrome (RDS) is the major cause of morbidity and mortality in premature infants. The primary etiology of the RDS is developmental immaturity of surfactant production. However, there is significant heterogeneity in pulmonary outcomes among infants of the same gestational age who have similar clinical risk factors. Studies suggest a significant genetic contribution to the risk of RDS. Genetic variations that are clinically insignificant among term infants may contribute to preterm infants' susceptibility to RDS. The specific aims of the proposal are 1) to examine if common genetic variations (single nucleotide polymorphisms) in the genes that code for Surfactant Proteins A, B, and C and ATP binding cassette transporter 3 are associated with RDS, and 2) to evaluate if severity of RDS is associated with these genetic variations. To accomplish these aims, we will employ a unique setting, the Northern California Kaiser Permanente Medical Care Program, which has a large defined population (>35,000 births/year), integrated information systems, and readily available critical information including an electronic medical record, radiology results, and laboratory test results. Using a nested case control design, we will obtain DMAsamples from infants with RDS (n~160) and controls matched by gestational age, gender, and ethnicity. Conditional multivariate logistic regression techniques will be used to evaluate for associations between these genetic variants and RDS. In the infants with RDS, we will use multivariate linear regression techniques to compare measures of RDS severity (duration of supplemental oxygen use and duration of assisted ventilation) between infants who have genetic variants and those who do not, controlling for confounders such as gestational age. Common variations in an infant's genetic code may explain why some infants develop RDS or have more severe disease. This variation may not be important unless the infant is born prematurely or has other risk factors. Knowing if an infant has any of these common variations may allow physicians to customize prevention and treatment strategies, based upon this genetic information.

候选人的长期职业目标是成为一名独立研究人员，他们将整合 遗传流行病学的方法与卫生服务和临床流行病学一起使用的方法 新生儿的照顾。 呼吸窘迫综合征（RDS）是早产儿发病和死亡率的主要原因。 RDS的主要病因是表面活性剂产生的发育不成熟。但是，有 同一胎龄的肺癌的显着异质性 类似的临床风险因素。研究表明，对RD的风险有重大遗传贡献。遗传 临床婴儿在临床上微不足道的变异可能会导致早产儿 对RD的敏感性。该提案的具体目的是1）检查是否常见遗传变异 （单核苷酸多态性）在代码表面活性剂蛋白A，B和C和ATP的基因中 绑定的盒式转运蛋白3与RDS相关，2）评估RD的严重程度是否为 与这些遗传变异有关。为了实现这些目标，我们将采用独特的环境， 北加州Kaiser Permanente医疗计划，该计划的人口众多 （> 35,000个/年的出生），综合信息系统以及随时可用的关键信息，包括 电子病历，放射学结果和实验室测试结果。使用嵌套的案例控制 设计，我们将从RDS（n〜160）的婴儿中获得DMASPLAPES，并且由妊娠匹配的对照 年龄，性别和种族。条件多元逻辑回归技术将用于 评估这些遗传变异和RD之间的关联。在患有RD的婴儿中，我们将使用 多元线性回归技术比较了RDS严重程度的度量（持续时间 具有遗传变异的婴儿之间的补充用氧和辅助通风持续时间 那些不这样做的人，控制胎龄等混杂因素。 婴儿遗传密码的常见变化可能解释了为什么有些婴儿会发展RD或更多 严重疾病。除非婴儿过早出生或有其他 风险因素。知道婴儿是否具有这些常见变异可能会允许医生自定义 基于此遗传信息的预防和治疗策略。