Cloning, expression and genomic structure of human LMX1A, and variant screening in Pima Indians

LIM-homeodomain containing protein LMX1A activates transcription of the insulin gene. The human LMX1A gene maps to 1q22-q23, a region identified as a putative type 2 diabetes mellitus (T2DM) locus in several different populations. We analyzed LMX1A as a positional and biological candidate gene for T2DM in the Pima Indians, in whom a linkage of T2DM to 1q21-q23 has been previously reported. In the present study, we describe the cloning, expression and genomic organization of the LMX1A gene, which is composed of 11 exons spanning approximately 151 kb. In addition to a transcript encoding the predicted full-length protein of 382 amino acids, we identified two truncated cDNA forms produced via additional transcription start sites and alternative splicing. We identified seven single nucleotide polymorphisms (SNPs) throughout the LMX1A locus and determined allele frequency distributions in 150 diabetic and 150 unaffected Pimas. We did not find evidence for association of any LMX1A SNPs with T2DM and conclude that LMX1A does not contribute significantly to T2DM etiology in Pima Indians.