title: SNPs rs4656317 and rs12071048 located within an enhancer in FCGR3A are in strong linkage disequilibrium with rs396991 and influence NK cell-mediated ADCC by transcriptional regulation.
abstract: CD16 receptors are mainly expresses on the surface of NK cells and mediate antibody-dependent cellular cytotoxicity (ADCC). The authors previously reported that NK cell-mediated ADCC is influenced by the single nucleotide polymorphism (SNP) rs396991 (T>G; F158V), and the structure and expression levels of CD16 differed among these genotypes. The authors examined haplotype frequency distributions among rs396991 and other SNPs, rs10917571 (G>T), rs4656317 (C>G), and rs12071048 (G>A), located in an enhancer of the FCGR3A gene. A total of 101 healthy Japanese were genotyped for the presence of these SNPs. The authors also measured ADCC activity, FCGR3A transcript levels, and surface CD16 expression on NK cells. We found that the regulatory SNPs (rSNPs) rs4656317 and rs12071048 were in strong linkage disequilibrium with rs396991. These two SNPs with major alleles had higher ADCC activity than those with minor alleles. In addition, FCGR3A transcript levels and surface CD16 expression levels were regulated by these SNPs. These findings suggest that NK cell-mediated ADCC could be influenced by transcriptional regulation of these rSNPs. These findings help to clarify our understanding of the linkage disequilibrium among functional SNPs in the FCGR3A gene, and provide a resource for investigating the roles of functional SNPs in NK cell-mediated ADCC.
authors.affiliation: Department of Medical Technology, Kagawa Prefectural University of Health Sciences, 281-1 Hara, Mure-cho, Takamatsu, Kagawa 761-0123, Japan; Subdivision of Biomedical Laboratory Sciences, Graduate School of Health Sciences, Tokushima University, 3-18-15 Kuramoto-cho, Tokushima 770-850, Japan. Electronic address: oboshi@chs.pref.kagawa.jp.
authors.forename: Wataru
authors.initials: W
authors.lastname: Oboshi
authors.affiliation: Department of Clinical Technology, Hyogo College of Medicine Hospital, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan. Electronic address: nnnlifelife@hotmail.co.jp.
authors.forename: Toru
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: The Graduate School of Health Sciences, Kagawa Prefectural University of Health Sciences, 281-1 Hara, Mure-cho, Takamatsu, Kagawa 761-0123, Japan. Electronic address: yukimasa@chs.pref.kagawa.jp.
authors.forename: Nobuyasu
authors.initials: N
authors.lastname: Yukimasa
authors.affiliation: The Graduate School of Health Sciences, Kagawa Prefectural University of Health Sciences, 281-1 Hara, Mure-cho, Takamatsu, Kagawa 761-0123, Japan. Electronic address: kataokataiden@gmail.com.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Ueno
authors.affiliation: Department of Cells and Immunity Analytics, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima 770-8509, Japan. Electronic address: aki@medsci.tokushima-u.ac.jp.
authors.forename: Kensaku
authors.initials: K
authors.lastname: Aki
authors.affiliation: Subdivision of Biomedical Laboratory Sciences, Graduate School of Health Sciences, Tokushima University, 3-18-15 Kuramoto-cho, Tokushima 770-850, Japan. Electronic address: tomoki_gedachtnis@live.jp.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Tada
authors.affiliation: Department of Cells and Immunity Analytics, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima 770-8509, Japan. Electronic address: hosoi@medsci.tokushima-u.ac.jp.
authors.forename: Eiji
authors.initials: E
authors.lastname: Hosoi
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D000920:Antibody-Dependent Cell Cytotoxicity / Q000235:genetics*; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D005838:Genotype; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide; D017452:Receptors, IgG / Q000235:genetics*; D055815:Young Adult
chemical_list: C496124:FCGR3A protein, human; D017452:Receptors, IgG
keywords: Antibody-dependent cellular cytotoxicity; FcγRIIIa; Linkage disequilibrium mapping; Natural killer cells; Single nucleotide polymorphism