Evaluating the association of common PBX1 variants with type 2 diabetes.
BACKGROUND
PBX1 is a biological candidate gene for type 2 diabetes at the 1q21-q24 susceptibility locus. The aim of this study was to evaluate the association of common PBX1 variants with type 2 diabetes in French Caucasian subjects.


METHODS
Employing a case-control design, we genotyped 39 SNPs spanning the PBX1 locus in 3,093 subjects to test for association with type 2 diabetes.


RESULTS
Several PBX1 SNPs, including the G21S coding SNP rs2275558, were nominally associated with type 2 diabetes but the strongest result was obtained with the intron 2 SNP rs2792248 (P = 0.004, OR 1.20 [95% CI 1.06-1.37]). The SNPSpD multiple testing correction method gave a significance threshold of P = 0.002 for the 39 SNPs genotyped, indicating that the rs2792248 association did not survive multiple testing adjustment. SNP rs2792248 did not show evidence of association with the French 1q linkage signal (P = 0.31; weighted NPL score 2.16). None of the PBX1 SNPs nominally associated with type 2 diabetes were associated with a range of quantitative metabolic traits in the normoglycemic control subjects


CONCLUSIONS
The available data does not support a major influence of common PBX1 variants on type 2 diabetes susceptibility or quantitative metabolic traits. In order to make progress in identifying the elusive susceptibility variants in the 1q region it will be necessary to carry out further large association studies, meta-analyses of existing data from individual studies, and deep resequencing of the 1q region.
Duesing
Konsta
K
Genomic Medicine, Imperial College London, Hammersmith Campus, Du Cane Rd, London W12 0NN, UK. k.duesing@imperial.ac.uk
Charpentier
Guillaume
G
Marre
Michel
M
Tichet
Jean
J
Hercberg
Serge
S
Balkau
Beverley
B
Froguel
Philippe
P
Gibson
Fernando
F
D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002874:Chromosome Mapping; D015331:Cohort Studies; D004268:DNA-Binding Proteins / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005602:France / Q000453:epidemiology; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D040641:Quantitative Trait Loci
D004268:DNA-Binding Proteins; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D011518:Proto-Oncogene Proteins; C083400:PBX1 protein, human