title: Variations with modest effects have an important role in the genetic background of type 2 diabetes and diabetes-related traits.
abstract: The aim of the present study was to explore the role of variations with modest effects (previously identified by a large-scale meta-analysis in European populations) in the genetic background of type 2 diabetes (T2D) and diabetes-related traits in a Japanese population. We enrolled 2632 Japanese subjects with T2D and 2050 non-diabetic subjects. We analyzed nine single-nucleotide polymorphisms (SNPs), including rs340874 (PROX1), rs4607517 (GCK), rs2191349 (DGKB-TMEM195), rs7034200 (GLIS3), rs10885122 (ADRA2A), rs174550 (FADS1), rs11605924 (CRY2), rs10830963 (MTNR1B) and rs35767 (IGF1). rs340874 (PROX1) and rs174550 (FADS1) were significantly associated with T2D (P=0.0078, OR: 1.12; and P=0.0071, OR: 1.12, respectively). Subjects with more risk alleles related to nine SNPs had an increased risk of T2D (P=0.0017), as well as a higher fasting plasma glucose level (P=0.018), higher HbA(1c) level (P=0.013) and lower HOMA-β (P=0.033) compared with subjects who had fewer risk alleles. We identified a significant association of a SNP of FADS1 and a SNP near PROX1 with T2D in a Japanese population. The present findings suggest that inclusion of SNPs with a tendency to increase the disease risk captured more of the genetic background of T2D than that revealed by only assessing significant SNPs.
authors.affiliation: Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Hayato
authors.initials: H
authors.lastname: Fujita
authors.forename: Kazuo
authors.initials: K
authors.lastname: Hara
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Shojima
authors.forename: Momoko
authors.initials: M
authors.lastname: Horikoshi
authors.forename: Minoru
authors.initials: M
authors.lastname: Iwata
authors.forename: Yushi
authors.initials: Y
authors.lastname: Hirota
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Tobe
authors.forename: Susumu
authors.initials: S
authors.lastname: Seino
authors.forename: Takashi
authors.initials: T
authors.lastname: Kadowaki
mesh_terms: D000368:Aged; D044466:Asian People / Q000235:genetics*; D015415:Biomarkers / Q000032:analysis*; D001786:Blood Glucose / Q000378:metabolism; D016022:Case-Control Studies; D000090943:Delta-5 Fatty Acid Desaturase; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007328:Insulin / Q000378:metabolism; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D000090943:Delta-5 Fatty Acid Desaturase; D007328:Insulin; C000716847:FADS1 protein, human