Heterogeneity in gene loci associated with type 2 diabetes on human chromosome 20q13.1

Genomics. 2008 Oct;92(4):226-34. doi: 10.1016/j.ygeno.2008.06.004. Epub 2008 Aug 9.


Human chromosome 20q12-q13.1 has been linked to type 2 diabetes mellitus (T2DM) in multiple studies. We screened a 5.795-Mb region for diabetes-related susceptibility genes in a Caucasian cohort of 310 controls and 300 cases with T2DM and end-stage renal disease (ESRD), testing 390 SNPs for association with T2DM-ESRD. The most significant SNPs were found in the perigenic regions: HNF4A (hepatocyte nuclear factor 4alpha), SLC12A5 (potassium-chloride cotransporter member 5), CDH22 (cadherin-like 22), ELMO2 (engulfment and cell motility 2), SLC13A3 (sodium-dependent dicarboxylate transporter member 3), and PREX1 (phosphatidylinositol 3,4,5-triphosphate-dependent RAC exchanger 1). Haplotype analysis found six haplotype blocks globally associated with disease (p<0.05). We replicated the PREX1 SNP association in an independent case-control T2DM population and inferred replication of CDH22, ELMO2, SLC13A3, SLC12A5, and PREX1 using in silico perigenic analysis of two T2DM Genome-Wide Association Study data sets. We found substantial heterogeneity between study results.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Cadherins / genetics
  • Case-Control Studies
  • Chromosomes, Human, Pair 20 / genetics*
  • Cytoskeletal Proteins / genetics
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetic Nephropathies / genetics*
  • Genetic Predisposition to Disease*
  • Guanine Nucleotide Exchange Factors / genetics
  • Humans
  • Kidney Failure, Chronic / genetics*
  • Polymorphism, Single Nucleotide*
  • Quantitative Trait Loci / genetics*
  • White People / genetics


  • Adaptor Proteins, Signal Transducing
  • Cadherins
  • Cytoskeletal Proteins
  • ELMO2 protein, human
  • Guanine Nucleotide Exchange Factors
  • PREX1 protein, human
  • CDH22 protein, human