title: Genetic polymorphisms of PCSK2 are associated with glucose homeostasis and progression to type 2 diabetes in a Chinese population.
abstract: Proprotein convertase subtilisin/kexin type 2 (PCSK2) is a prohormone processing enzyme involved in insulin and glucagon biosynthesis. We previously found the genetic polymorphism of PCSK2 on chromosome 20 was responsible for the linkage peak of several glucose homeostasis parameters. The aim of this study is to investigate the association between genetic variants of PCSK2 and glucose homeostasis parameters and incident diabetes. Total 1142 Chinese participants were recruited from the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance (SAPPHIRe) family study, and 759 participants were followed up for 5 years. Ten SNPs of the PCSK2 gene were genotyped. Variants of rs6044695 and rs2284912 were associated with fasting plasma glucose, and variants of rs2269023 were associated with fasting plasma glucose and 1-hour plasma glucose during OGTT. Haplotypes of rs4814605/rs1078199 were associated with fasting plasma insulin levels and HOMA-IR. Haplotypes of rs890609/rs2269023 were also associated with fasting plasma glucose, fasting insulin and HOMA-IR. In the longitudinal study, we found individuals carrying TA/AA genotypes of rs6044695 or TC/CC genotypes of rs2284912 had lower incidence of diabetes during the 5-year follow-up. Our results indicated that PCSK2 gene polymorphisms are associated with pleiotropic effects on various traits of glucose homeostasis and incident diabetes.
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, Taipei 10002, Taiwan.
authors.forename: Tien-Jyun
authors.initials: TJ
authors.lastname: Chang
authors.affiliation: Department of Bioinformatics and Biostatistics, National Health Research Institutes, Zhunan Town, Miaoli County 35053, Taiwan.
authors.forename: Yen-Feng
authors.initials: YF
authors.lastname: Chiu
authors.affiliation: Department of Internal Medicine, Taichung Veterans General Hospital, Taichung 40705, Taiwan.
authors.forename: Wayne H-H
authors.initials: WH
authors.lastname: Sheu
authors.affiliation: Division of Endocrinology and Metabolism, Taipei Veterans General Hospital, Taipei 11217, Taiwan.
authors.forename: Kuang-Chung
authors.initials: KC
authors.lastname: Shih
authors.affiliation: Section of General Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei 11127, Taiwan.|Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei 11221, Taiwan.
authors.forename: Chii-Min
authors.initials: CM
authors.lastname: Hwu
authors.affiliation: Division of Cardiovascular Medicine, Falk Cardiovascular Research Building, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Quertermous
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.
authors.forename: Yuh-Shan
authors.initials: YS
authors.lastname: Jou
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, Taipei 10002, Taiwan.
authors.forename: Shan-Shan
authors.initials: SS
authors.lastname: Kuo
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, Taipei 10002, Taiwan.|Graduate Institute of Medical Genomics and Proteomics, National Taiwan University College of Medicine, Taipei 10055 Taiwan.
authors.forename: Yi-Cheng
authors.initials: YC
authors.lastname: Chang
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, Taipei 10002, Taiwan.|Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei 10055, Taiwan.
authors.forename: Lee-Ming
authors.initials: LM
authors.lastname: Chuang
mesh_terms: D044466:Asian People / Q000235:genetics*; D001786:Blood Glucose / Q000378:metabolism*; D002681:China / Q000453:epidemiology; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006239:Haplotypes / Q000235:genetics; D006706:Homeostasis / Q000235:genetics*; D006801:Humans; D015994:Incidence; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D045706:Proprotein Convertase 2 / Q000235:genetics*
chemical_list: D001786:Blood Glucose; C581329:PCSK2 protein, human; D045706:Proprotein Convertase 2