糖尿病遗传学.pptVIP

Increase in T2D in Children Most T2D children were females from minority populations Mean age at onset was around puberty Many had a family history of T2D Environmental Risk Factors in T2D Obesity Increases risk of developing T2D Defined as: 120% of ideal body weight Body mass index (BMI) 30 k / m2 Likely related to the increase in T2D ~80% newly diagnosed cases due to obesity Higher association with abdominal or central obesity Assessed by measuring the waist-to- hip ratio Environmental Risk Factors in T2D Physical Activity Increases risk of developing T2D Exercise Controls weight Improves glucose and lipid metabolism Is inversely related to body mass index Lifestyle interventions decreased risk of progression of impaired glucose tolerance to T2D by ~60% Genetics and T2D Individuals with a positive family history are about 2-6 times more likely to develop T2D than those with a negative family history Risk ~40% if T2D parent; ~80% if 2 T2D parents Higher concordance for MZ versus DZ twins Has been difficult to find genes for T2D Late age at onset Polygenic inheritance Multifactorial inheritance Finding Genes for T2D Candidates selected because they are involved in Pancreatic beta cell function Insulin action / glucose metabolism Energy intake / expenditure Lipid metabolism Genome wide screens Nothing is assumed about disease etiology Genome wide association studies Current approach based on thousands of cases and controls Challenges in Finding Genes Inadequate sample sizes Multiplex families Cases and controls Difficult to define the phenotype Reduced penetrance Influence of environmental factors Gene-gene interactions Variable age at onset Failure to replicate findings Genes identified have small effects CAPN10 – NIDDM1 Chromosome 2q37.3 (OMIM 601283) Encodes an intracellular calcium-dependent cytoplasmic protease that is ubiquitously expressed May modulate activity of enzymes and/or apoptosis Likely involves insulin secretion and resistance