An autosomal genomic scan for loci linked to prediabetic phenotypes in Pima Indians.
Type 2 diabetes mellitus is a common chronic disease that is thought to have a substantial genetic basis. Identification of the genes responsible has been hampered by the complex nature of the syndrome. Abnormalities in insulin secretion and insulin action predict the development of type 2 diabetes and are, themselves, highly heritable traits. Since fewer genes may contribute to these precursors of type 2 diabetes than to the overall syndrome, such genes may be easier to identify. We, therefore, undertook an autosomal genomic scan to identify loci linked to prediabetic traits in Pima Indians, a population with a high prevalence of type 2 diabetes. 363 nondiabetic Pima Indians were genotyped at 516 polymorphic microsatellite markers on all 22 autosomes. Linkage analyses were performed using three methods (single-marker, nonparametric multipoint [MAPMAKER/SIBS], and variance components multipoint). These analyses provided evidence for linkage at several chromosomal regions, including 3q21-24 linked to fasting plasma insulin concentration and in vivo insulin action, 4p15-q12 linked to fasting plasma insulin concentration, 9q21 linked to 2-h insulin concentration during oral glucose tolerance testing, and 22q12-13 linked to fasting plasma glucose concentration. These results suggest loci that may harbor genes contributing to type 2 diabetes in Pima Indians. None of the linkages exceeded a LOD score of 3.6 (a 5% probability of occurring in a genome-wide scan). These findings must, therefore, be considered tentative until extended in this population or replicated in others.
Pratley
R E
RE
Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona 85016, USA. Richard_Pratley@nih.gov
Thompson
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DB
Prochazka
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M
Baier
L
L
Mott
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D
Ravussin
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E
Sakul
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H
Ehm
M G
MG
Burns
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DK
Foroud
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T
Garvey
W T
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Hanson
R L
RL
Knowler
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Bennett
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Bogardus
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D000328:Adult; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D005838:Genotype; D006801:Humans; D007198:Indians, North American / Q000235:genetics*; D007328:Insulin / Q000097:blood; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D011110:Polymorphism, Genetic; D011236:Prediabetic State / Q000097:blood / Q000235:genetics*
D007328:Insulin