title: Influence of MILR1 promoter polymorphism on expression levels and the phenotype of atopy.
abstract: The recently identified cell surface immunoreceptor MILR1 (mast cell immunoglobulin-like receptor 1; synonyms, Allergin-1) has been shown to suppress immunoglobulin E (IgE)-mediated, mast cell-dependent responses in both mice and humans. We performed a mutation search of MILR1 together with a genetic association study to determine whether polymorphisms in MILR1 are associated with atopy in human. Mutation screening of MILR1 was performed using DNA from 146 unrelated Japanese. Genotyping of the identified polymorphisms was done with 1505 individuals from the general Japanese adult population. Atopy, as defined by positive responses for specific IgEs against at least one of the 26 common allergens, was evaluated using MAST-26. Five polymorphisms (rs6504230, c.-170_-166delAGGAA, rs8071835, rs143526766 and rs12936887) and two rare missense variants (Val273Ala and Leu311Val) were identified by mutation screening. The C allele of rs6504230 had protective effects against atopy (P=0.002). A luciferase reporter assay using the promoter region of MILR1 revealed that the C allele of rs6504230 was associated with increased expression of MILR1, which was in accordance with the results of expression quantitative trait loci analysis using human leukocytes. Our data indicates that the rs6504230 polymorphism affects MILR1 expression levels in humans, leading to a susceptibility to producing specific IgE antibodies against common allergens.
authors.affiliation: Department of Medical Genetics, Faculty of Medicine, University of Tsukuba, Tsukuba City, Ibaraki, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Nanatsue
authors.affiliation: Department of Medical Genetics, Faculty of Medicine, University of Tsukuba, Tsukuba City, Ibaraki, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ninomiya
authors.affiliation: Department of Medical Genetics, Faculty of Medicine, University of Tsukuba, Tsukuba City, Ibaraki, Japan.
authors.forename: Mio
authors.initials: M
authors.lastname: Tsuchiya
authors.affiliation: 1] Department of Immunology, Faculty of Medicine, University of Tsukuba, Tsukuba City, Ibaraki, Japan [2] Japan Science and Technology Agency (JST), Core Research for Evolutional Science and Technology (CREST), Tokyo, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Tahara-Hanaoka
authors.affiliation: 1] Department of Immunology, Faculty of Medicine, University of Tsukuba, Tsukuba City, Ibaraki, Japan [2] Japan Science and Technology Agency (JST), Core Research for Evolutional Science and Technology (CREST), Tokyo, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Shibuya
authors.affiliation: Department of Respiratory Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba City, Ibaraki, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Masuko
authors.affiliation: Department of Respiratory Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba City, Ibaraki, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Sakamoto
authors.affiliation: Department of Respiratory Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba City, Ibaraki, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Hizawa
authors.affiliation: Department of Medical Genetics, Faculty of Medicine, University of Tsukuba, Tsukuba City, Ibaraki, Japan.
authors.forename: Tadao
authors.initials: T
authors.lastname: Arinami
authors.affiliation: 1] Department of Medical Genetics, Faculty of Medicine, University of Tsukuba, Tsukuba City, Ibaraki, Japan [2] Japan Science and Technology Agency (JST), Core Research for Evolutional Science and Technology (CREST), Tokyo, Japan.
authors.forename: Emiko
authors.initials: E
authors.lastname: Noguchi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000485:Allergens / Q000276:immunology; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D004252:DNA Mutational Analysis; D015870:Gene Expression; D005787:Gene Frequency; D005838:Genotype; D057809:HEK293 Cells; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000235:genetics* / Q000276:immunology; D007073:Immunoglobulin E / Q000276:immunology; D020014:K562 Cells; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011971:Receptors, Immunologic / Q000235:genetics* / Q000276:immunology; D055815:Young Adult
chemical_list: D000485:Allergens; C000596249:MILR1 protein, human; D011971:Receptors, Immunologic; D007073:Immunoglobulin E