title: Frequency and clinical implication of the R450H mutation in the thyrotropin receptor gene in the Japanese population detected by Smart Amplification Process 2.
abstract: In Japanese pediatric patients with thyrotropin (TSH) resistance, the R450H mutation in TSH receptor gene (TSHR) is occasionally observed. We studied the frequency and clinical implication of the R450H mutation in TSHR in the general population of Japanese adults using smart amplification process 2 (SmartAmp2). We designed SmartAmp2 primer sets to detect this mutation using a drop of whole blood. We analyzed thyroid function, antithyroid antibodies, and this mutation in 429 Japanese participants who had not been found to have thyroid disease. Two cases without antithyroid antibodies were heterozygous for the R450H mutation in TSHR. Thus, the prevalence of this mutation was 0.47% in the general population and 0.63% among those without antithyroid antibodies. Their serum TSH concentrations were higher than the average TSH concentration not only in subjects without antithyroid antibodies but also in those with antithyroid antibodies. The R450H mutation in TSHR is relatively common in the Japanese population and potentially affects thyroid function. The present study demonstrates that the SmartAmp2 method is useful to detect the R450H mutation in TSHR, which is one of the common causes of TSH resistance in the Japanese population.
authors.affiliation: Department of Clinical Laboratory Medicine, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan.
authors.forename: Katsuhiko
authors.identifier: 0000-0002-6119-4158
authors.initials: K
authors.lastname: Tsunekawa
authors.affiliation: Department of Clinical Laboratory Medicine, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan.
authors.forename: Yoshimaro
authors.initials: Y
authors.lastname: Yanagawa
authors.affiliation: Department of Clinical Laboratory Medicine, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Aoki
authors.affiliation: Department of Clinical Laboratory Medicine, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Morimura
authors.affiliation: Department of Clinical Laboratory Medicine, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Araki
authors.affiliation: Department of Clinical Laboratory Medicine, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Kimura
authors.affiliation: Department of Clinical Laboratory Medicine, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Ogiwara
authors.affiliation: Department of Clinical Laboratory Medicine, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Kotajima
authors.affiliation: Department of Health and Physical Education, Faculty of Education, Gunma University, Maebashi 371-8510, Japan.
authors.forename: Masumi
authors.initials: M
authors.lastname: Yanagawa
authors.affiliation: Department of Clinical Laboratory Medicine, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Murakami
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D001323:Autoantibodies / Q000276:immunology; D005260:Female; D006579:Heterozygote; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D059645:Mutation Rate; D016133:Polymerase Chain Reaction / Q000379:methods*; D011989:Receptors, Thyrotropin / Q000235:genetics*; D013961:Thyroid Gland / Q000503:physiopathology; D013972:Thyrotropin
chemical_list: D001323:Autoantibodies; D011989:Receptors, Thyrotropin; D013972:Thyrotropin