Do non-insulin-dependent diabetes mellitus (NIDDM) and insulin-dependent diabetes mellitus (IDDM) share genetic susceptibility loci? An analysis of putative IDDM susceptibility regions in familial NIDDM.
Non-insulin-dependent diabetes mellitus (NIDDM) has been viewed as genetically and physiologically distinct from insulin-dependent diabetes mellitus (IDDM), yet many of the recently suggested IDDM susceptibility loci are likely to increase the risk of diabetes through nonautoimmune mechanisms. To test the hypothesis that the IDDM susceptibility loci include important NIDDM susceptibility loci, we tested the linkage of 14 putative susceptibility regions with NIDDM among families and sibling pairs of Northern European descent. All regions were tested with highly informative microsatellite (simple tandem repeat) polymorphisms in up to 166 affected individuals from 42 families using both parametric and nonparametric methods (149 pairs for sibling pair analyses). We found no evidence for linkage to the majority of loci, including loci that appeared to be linked to IDDM in more than one study. We report some evidence for shared susceptibility for regions on chromosomes 1, 2, and 6. The best evidence based on multilocus affected pedigree member (APM) analysis of markers near D1S191 suggested linkage at P value .0001. This region has not yet been confirmed as an IDDM locus, and our analyses could represent a false-positive result. The role of these three regions will only be clarified by testing in additional families. In combination with other investigations in our laboratory for chromosome 11 susceptibility regions, our data generally do not provide convincing evidence that IDDM and NIDDM share common genetic factors among families of Northern European descent with ascertainment of two or more NIDDM siblings.
Elbein
S C
SC
Division of Endocrinology, Diabetes and Metabolism, Department of Veterans Affairs Medical Center and University of Utah, Salt Lake City, USA.
Hoffman
M D
MD
Mayorga
R A
RA
Barrett
K L
KL
Leppert
M
M
Hasstedt
S
S
D000328:Adult; D000368:Aged; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D002880:Chromosomes, Human, Pair 11; D002889:Chromosomes, Human, Pair 2; D002896:Chromosomes, Human, Pair 6; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D004198:Disease Susceptibility; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D011110:Polymorphism, Genetic
D005819:Genetic Markers