title: Association of the proprotein convertase subtilisin/kexin-type 2 (PCSK2) gene with type 2 diabetes in an African American population.
abstract: In a genome-wide scan for type 2 diabetes (T2DM) in African American (AA) families, ordered subsets analysis (OSA) provided evidence for linkage to chromosome 20p in a subset with later age at diagnosis (max LOD 2.57, P=0.008). The proprotein convertase subtilisin/kexin-type 2 (PCSK2) gene is within the LOD-1 interval of this linkage peak. Twenty-nine single nucleotide polymorphisms (SNPs) were genotyped across this gene in 380 unrelated AA individuals with T2DM and end-stage renal disease (T2DM-ESRD), 278 AA controls, 96 European Americans (EA) and 120 Yoruba Nigerian (YRI) controls. In addition, 22 ancestry-informative markers (AIMs) were genotyped in all AA subjects, 120 YRI, and 282 EA controls. ADMIXMAP was used to model the distributions of admixture and generate score tests of allelic and haplotypic association. Association with T2DM was observed among 4 SNPs: rs2021785 (admixture-adjusted Pa=0.00014), rs1609659 (Pa=0.028), rs4814597 (Pa=0.039) and rs2269023 (Pa=0.043). None of the PCSK2 SNPs were associated with age at T2DM diagnosis. A variant in the PCKS2 gene, rs2021785, appears to play a role in susceptibility to T2DM in this AA population.
authors.affiliation: Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
authors.forename: Tennille S
authors.initials: TS
authors.lastname: Leak
authors.forename: Keith L
authors.initials: KL
authors.lastname: Keene
authors.forename: Carl D
authors.initials: CD
authors.lastname: Langefeld
authors.forename: Carla J
authors.initials: CJ
authors.lastname: Gallagher
authors.forename: Josyf C
authors.initials: JC
authors.lastname: Mychaleckyj
authors.forename: Barry I
authors.initials: BI
authors.lastname: Freedman
authors.forename: Donald W
authors.initials: DW
authors.lastname: Bowden
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Rich
authors.forename: Michèle M
authors.initials: MM
authors.lastname: Sale
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics*; D017677:Age Distribution; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000201:enzymology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D045706:Proprotein Convertase 2 / Q000235:genetics*
chemical_list: D045706:Proprotein Convertase 2