Linkage analysis of 19 candidate regions for insulin resistance in familial NIDDM.
As part of an ongoing search for diabetes susceptibility loci, we tested linkage with non-insulin-dependent diabetes mellitus (NIDDM) for 19 candidate loci or regions chosen for their potential to affect directly or indirectly the action of insulin. Loci were associated with insulin resistance, known effects on lipid metabolism, or effects on glucose metabolism or insulin action. Loci included the insulin-responsive (GLUT4) glucose transporter, hexokinase 2, glucagon, growth hormone, insulin receptor substrate 1 (IRS1), phosphoenolpyruvate carboxykinase, hepatic and muscle forms of pyruvate kinase, hepatic phosphofructokinase, the apolipoprotein B and the apolipoprotein A2 cluster, lipoprotein lipase, hepatic triglyceride lipase, the very-low-density-lipoprotein receptor, and the Pima insulin resistance locus on chromosome 4. For several candidates, no specific informative marker was available; consequently, we tested the surrounding region with highly informative markers. These regions included the diabetes-associated ras-like gene, rad, and the cholesterol ester-transfer gene, both mapped to chromosome 16. Additionally, we tested for linkage with markers at the tumor necrosis factor-alpha gene and the Friedreich's ataxia region. All regions were tested for linkage with microsatellite polymorphisms in > 450 individuals from a minimum of 16 Caucasian families under parametric (LINKAGE 5.1) and nonparametric (affected pedigree member) models.(ABSTRACT TRUNCATED AT 250 WORDS)
Elbein
S C
SC
Division of Endocrinology, Metabolism and Diabetes, Veterans Affairs Medical Center, Salt Lake City, Utah 84148, USA.
Chiu
K C
KC
Hoffman
M D
MD
Mayorga
R A
RA
Bragg
K L
KL
Leppert
M F
MF
D000328:Adult; D000367:Age Factors; D000368:Aged; D016633:Apolipoprotein A-II / Q000235:genetics; D001483:Base Sequence; D002874:Chromosome Mapping; D002877:Chromosomes, Human; D017931:DNA Primers; D003920:Diabetes Mellitus / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D004798:Enzymes / Q000235:genetics; D005799:Genes, Dominant; D005808:Genes, Recessive; D006580:Genetic Carrier Screening; D008040:Genetic Linkage; D013006:Growth Hormone / Q000235:genetics; D006801:Humans; D055504:Insulin Receptor Substrate Proteins; D007333:Insulin Resistance / Q000235:genetics*; D008126:Lod Score; D008875:Middle Aged; D008969:Molecular Sequence Data; D009765:Obesity; D010750:Phosphoproteins / Q000235:genetics; D011506:Proteins / Q000235:genetics; D044465:White People / Q000235:genetics
D016633:Apolipoprotein A-II; D017931:DNA Primers; D004798:Enzymes; C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; D010750:Phosphoproteins; D011506:Proteins; D013006:Growth Hormone