title: Heterogeneity in gene loci associated with type 2 diabetes on human chromosome 20q13.1.
abstract: 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.
authors.affiliation: Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Bento
authors.forename: N D
authors.initials: ND
authors.lastname: Palmer
authors.forename: M
authors.initials: M
authors.lastname: Zhong
authors.forename: B
authors.initials: B
authors.lastname: Roh
authors.forename: J P
authors.initials: JP
authors.lastname: Lewis
authors.forename: M R
authors.initials: MR
authors.lastname: Wing
authors.forename: H
authors.initials: H
authors.lastname: Pandya
authors.forename: B I
authors.initials: BI
authors.lastname: Freedman
authors.forename: C D
authors.initials: CD
authors.lastname: Langefeld
authors.forename: S S
authors.initials: SS
authors.lastname: Rich
authors.forename: D W
authors.initials: DW
authors.lastname: Bowden
authors.forename: J C
authors.initials: JC
authors.lastname: Mychaleckyj
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D015820:Cadherins / Q000235:genetics; D016022:Case-Control Studies; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics*; D003598:Cytoskeletal Proteins / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics; D006801:Humans; D007676:Kidney Failure, Chronic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015820:Cadherins; D003598:Cytoskeletal Proteins; C486678:ELMO2 protein, human; D020662:Guanine Nucleotide Exchange Factors; C453280:PREX1 protein, human; C099417:CDH22 protein, human