title: No evidence for association of the ENPP1 (PC-1) K121Q variant with risk of type 2 diabetes in a Japanese population.
abstract: Ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1, also known as PC-1) inhibits insulin signal transduction pathway(s). Previous studies have demonstrated the K121Q variant of the ENPP1 gene to have a significant functional role in determining susceptibility to insulin resistance and type 2 diabetes (T2D). To assess whether the K121Q variant has any impact on T2D in Japanese, we undertook an extensive case-control association study using a total of 911 unrelated Japanese T2D patients and 876 control subjects. No significant difference was observed in either genotype distribution (P=0.95) or allele frequency (P=0.83) between T2D and control groups. Notably, the frequency of the ancestral Q121 allele, which is also present in other primates, was quite high in African-Americans, and showed a marked ethnic variation (77.3% in African-Americans, 16.7% in European Americans, 10.5% in Japanese and 4.2% in Han Chinese). Consequently, the pairwise F(ST )value (a classic measure of genetic distance between pairs of population) showed highly significant differentiations between African-American and non-African-American populations (F(ST)>0.3). Our results indicated that the K121Q variant of the ENPP1 gene has very little, if any, impact on T2D susceptibility in Japanese, but may play a role in the inter-ethnic variability in insulin resistance and T2D.
authors.affiliation: Division of Genetic Information, Institute for Genome Research, The University of Tokushima, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan.
authors.forename: Parvaneh
authors.initials: P
authors.lastname: Keshavarz
authors.affiliation: Division of Genetic Information, Institute for Genome Research, The University of Tokushima, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan. hinoue@genome.tokushima-u.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Inoue
authors.affiliation: Division of Genetic Information, Institute for Genome Research, The University of Tokushima, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Sakamoto
authors.affiliation: Division of Genetic Information, Institute for Genome Research, The University of Tokushima, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Kunika
authors.affiliation: Division of Genetic Information, Institute for Genome Research, The University of Tokushima, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan.
authors.forename: Toshihito
authors.initials: T
authors.lastname: Tanahashi
authors.affiliation: Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Nakamura
authors.affiliation: Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan.
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Yoshikawa
authors.affiliation: Department of Orthopedics, Institute of Health Biosciences, The University of Tokushima, Tokushima, Japan.
authors.forename: Natsuo
authors.initials: N
authors.lastname: Yasui
authors.affiliation: Department of Ophthalmology and Visual Neuroscience, Institute for Health Biosciences, The University of Tokushima, Tokushima, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shiota
authors.affiliation: Division of Genetic Information, Institute for Genome Research, The University of Tokushima, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan.
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Itakura
mesh_terms: D001741:Black or African American / Q000235:genetics; D000483:Alleles; D019943:Amino Acid Substitution; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology* / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D007564:Japan; D008297:Male; D010727:Phosphoric Diester Hydrolases / Q000235:genetics*; D011755:Pyrophosphatases / Q000235:genetics*; D012307:Risk Factors; D044465:White People / Q000235:genetics
chemical_list: D010727:Phosphoric Diester Hydrolases; C065962:ectonucleotide pyrophosphatase phosphodiesterase 1; D011755:Pyrophosphatases