Evaluation of DLG2 as a positional candidate for disposition index in African-Americans from the IRAS Family Study.
OBJECTIVE
Evaluate discs large homolog 2 (DLG2) as a positional candidate gene for disposition index (DI) in the Insulin Resistance Atherosclerosis Family Study (IRAS-FS) African-American sample.


METHODS
SNPs (n=193) were selected for genotyping in 580 African-American individuals using a modified tagging algorithm. Follow-up genotyping was carried out within regions associated with DI. A subset of highly associated, uncorrelated SNPs was used as covariates in the linkage analysis to assess their contribution to linkage.


RESULTS
Evidence of association with DI was observed at the DLG2 locus (admixture-adjusted P=0.050-8.7 x 10(-5)) with additional signals observed in follow-up genotyping of 17 SNPs (P=0.033-0.0012). Inclusion of highly associated, uncorrelated SNPs as covariates in the linkage analysis explained linkage at the DLG2 locus (90.8 cM) and reduced the maximal LOD score (72.0 cM) from 4.37 to 3.71.


CONCLUSIONS
Evidence of association and an observed contribution to evidence for linkage to DI was observed for SNPs in DLG2 genotyped on the African-American individuals from the IRAS-FS. Although not the only gene in the region, these results suggest that variation at the DLG2 locus contributes to maintenance of glucose homeostasis through regulation of insulin sensitivity and beta-cell function as measured by DI.
Palmer
Nicholette D
ND
Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Mychaleckyj
Josyf C
JC
Langefeld
Carl D
CD
Ziegler
Julie T
JT
Williams
Adrienne H
AH
Bryer-Ash
Michael
M
Bowden
Donald W
DW
D000328:Adult; D000465:Algorithms; D044383:Black People / Q000235:genetics*; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D002874:Chromosome Mapping; D005190:Family; D005260:Female; D056726:Genetic Association Studies; D014644:Genetic Variation; D005838:Genotype; D005947:Glucose / Q000378:metabolism; D051528:Guanylate Kinases / Q000235:genetics*; D006706:Homeostasis; D006801:Humans; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000502:physiology; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D001741:Black or African American
D001786:Blood Glucose; D025521:Tumor Suppressor Proteins; C496468:DLG2 protein, human; D051528:Guanylate Kinases; D005947:Glucose