Telomere attrition and diabetes risk in American Indians

美洲印第安人的端粒磨损和糖尿病风险

• 批准号: 8531916
• 负责人: Jinying Zhao
• 金额: $ 27.75万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8531916
• 关键词: 20 year old; Accounting; Affect; Age; Aging; Alcohol consumption; American Indians; Behavior Therapy; Behavioral; Behavioral Genetics; Biological Aging; Biological Markers; Cell Cycle; Cell division; Chromosomal Stability; Chromosomes; Clinical; Clinical Data; DNA; DNA Sequence; Data; Diabetes Mellitus; Dietary intake; Disease; Distal; Educational Background; Employment Status; Ethnic group; Family; Family Study; Genetic; Genome Scan; Heart; Heritability; Income; Individual; Inflammation; Insulin Resistance; Lead; Length; Leukocytes; Life Style; Link; Maps; Marital Status; Measures; Mental Depression; Metabolic Diseases; Metabolic syndrome; Mitotic; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Participant; Pathogenesis; Pathway interactions; Phenotype; Physical activity; Prevalence; Psychophysiologic Disorders; Psychosocial Stress; Quality of life; Quantitative Trait Loci; Research; Risk; Risk Factors; Risk Reduction; Role; Sampling; Scanning; Series; Smoking; Stratification; Telomere Shortening; Time; Underserved Population; Variant; Visit; age related; base; cigarette smoking; cohort; diabetes risk; diabetic; diabetic patient; follow-up; genetic linkage analysis; genome-wide linkage; lifestyle intervention; prospective; psychosocial; socioeconomics; telomere

DESCRIPTION (provided by applicant): Telomeres are specialized DNA sequences at the end of each chromosome. Telomere length shortens progressively during each round of cell cycle and declines with aging, and thus has emerged as a valuable biomarker for biological aging and age-related disorders. Shorter telomeres have been associated with increased risk for type 2 diabetes and its related phenotypes. These associations, however, were primarily based on cross-sectional data, and therefore raise an important question as to whether shorter telomeres are a cause or a consequence of diabetes, or whether it is simply an epiphenomenon. Diabetes disproportionately affects American Indians. The prevalence of type 2 diabetes is, on average, 2-4 times higher than that in other ethnic groups. The objectives of this study are to delineate the prospective impact of telomere attrition on diabetes risk, and to determine genetic, behavioral and psychosocial predictors for accelerated telomere loss. Leukocyte telomere length will be measured by quantitative PCR in 4,565 DNA samples collected by the Strong Heart Family Study at two clinical visits (900 subjects examined at both visits, 2,765 examined at the second visit only). All DNA samples, well-characterized clinical data including follow-up data through December 2009 and data from a 10cM genome scan are already available for the proposed analyses. Specific aims: 1) To determine whether telomere attrition is associated with diabetes and its related phenotypes; 2) To identify genetic loci related to telomeric variation by a genome-wide linkage scan; 3) To determine behavioral, socioeconomic and psychosomatic predictors for accelerated telomere shortening in relation to diabetes risk. This is the first study to investigate prospectively the associations of telomere length and of telomere attrition rate with diabetes risk, and is also the first study to determine genetic, behavioral and psychosocial predictors for accelerated telomere erosion in this underserved population. If the proposed aims are achieved, we will be able to provide valuable information regarding a causal role of accelerated telomere loss in the pathogenesis of diabetes, thereby providing evidence for telomere length as a biomarker for diabetes and its associated disorders. The results will also provide important information for risk stratification in American Indians and other ethnic groups as well. Furthermore, this study will provide valuable information for lifestyle/behavioral interventions for diabetic risk reduction. We expect that this study will open new lines of research, and could potentially lead to critical discoveries that will accelerate the field of aging and diabetes as well as a wide range of metabolic disorders, and thus is of great significance.

描述（由申请人提供）：端粒是每个染色体末端的专门DNA序列。端粒长度在每一轮细胞周期中逐渐缩短，并且随着衰老而下降，因此已成为生物衰老和与年龄相关疾病的有价值的生物标志物。较短的端粒与2型糖尿病及其相关表型的风险增加有关。但是，这些关联主要基于横截面数据，因此提出了一个重要的问题，即较短的端粒是糖尿病的原因或结果，还是仅仅是epiphenomenon。糖尿病不成比例地影响美国印第安人。 2型糖尿病的患病率平均比其他族裔群体高2-4倍。这项研究的目的是描述端粒损耗对糖尿病风险的前瞻性影响，并确定加速端粒损失的遗传，行为和社会心理预测因子。白细胞端粒长度将通过定量PCR进行测量，在两次临床访问中通过强心脏家庭研究收集的4,565个DNA样品（两次访问时检查了900名受试者，仅在第二次访问时检查了2,765名受试者）。所有DNA样品，包括截至2009年12月的后续数据，包括随访数据以及10厘米基因组扫描的数据，已经进行了拟议的分析。具体目的：1）确定端粒损耗是否与糖尿病及其相关表型有关； 2）通过通过全基因组链接扫描来鉴定与端粒变异有关的遗传基因座； 3）确定与糖尿病风险有关的加速端粒缩短的行为，社会经济和心体预测因素。这是第一项研究，旨在研究端粒长度和端粒损耗率与糖尿病风险的关联，并且也是第一个确定这个不足的人群中加速端粒侵蚀的遗传，行为和心理心理预测指标的研究。如果实现了拟议的目标，我们将能够提供有关加速端粒损失在糖尿病发病机理中的因果作用的宝贵信息，从而提供了端粒长度作为糖尿病及其相关疾病的生物标志物的证据。结果还将为美国印第安人和其他种族的风险分层提供重要信息。此外，这项研究将为生活方式/行为干预措施提供有价值的信息，以减少糖尿病风险。我们预计这项研究将开放新的研究线，并可能导致关键发现，这些发现将加速衰老和糖尿病领域以及广泛的代谢障碍，因此具有重要意义。