A SNP in the ABCC11 gene is the determinant of human earwax type

Koh-ichiro Yoshiura^1, 2, Akira Kinoshita^1, 2, Takafumi Ishida³, Aya Ninokata³, Toshihisa Ishikawa⁴, Tadashi Kaname^2, 5, Makoto Bannai⁶, Katsushi Tokunaga⁶, Shunro Sonoda⁷, Ryoichi Komaki⁸, Makoto Ihara⁹, Vladimir A Saenko¹⁰, Gabit K Alipov¹¹, Ichiro Sekine¹¹, Kazuki Komatsu¹², Haruo Takahashi¹², Mitsuko Nakashima^1, 2, 13, Nadiya Sosonkina^1, 2, Christophe K Mapendano^1, 2, Mohsen Ghadami^1, 2, Masayo Nomura^1, 2, 14, De-Sheng Liang^2, 15, Nobutomo Miwa^1, 2, Dae-Kwang Kim¹⁶, Ariuntuul Garidkhuu¹⁷, Nagato Natsume¹⁷, Tohru Ohta^2, 18, Hiroaki Tomita¹⁹, Akira Kaneko²⁰, Mihoko Kikuchi²¹, Graciela Russomando²², Kenji Hirayama²¹, Minaka Ishibashi²³, Aya Takahashi²³, Naruya Saitou²³, Jeffery C Murray²⁴, Susumu Saito²⁵, Yusuke Nakamura^25, 26 & Norio Niikawa^1, 2

¹  Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

²  Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology, Kawaguchi, Japan.

³  Department of Biological Sciences, Graduate School of Science, University of Tokyo, Tokyo, Japan.

⁴  Department of Biomolecular Engineering, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Japan.

⁵  Department of Medical Genetics, University of the Ryukyu School of Medicine, Okinawa, Japan.

⁶  Department of Human Genetics, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.

⁷  Research and Development Center, Kagoshima University, Kagoshima, Japan.

⁸  Cosmetics Laboratory, Kanebo Cosmetics, Inc., Odawara, Japan.

⁹  Department of Radiation Biophysics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

¹⁰  International Health and Radiation Research, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

¹¹  Department of Molecular Pathology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

¹²  Department of Otolaryngology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

¹³  Department of Plastic and Reconstructive Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

¹⁴  Department of Dermatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

¹⁵  National Laboratory of Medical Genetics of China, Xiangya Hospital, Central South University, Changsha, China.

¹⁶  Department of Anatomy, Hanvit Institute for Medical Genetics, Keimyung University School of Medicine, Taegu, Korea.

¹⁷  Graduate School of Dentistry, Aichi Gakuin University, Nagoya, Japan.

¹⁸  Research Institute of Personalized Health Sciences, Health Science University of Hokkaido, Ishikari-Tobetsu, Japan.

¹⁹  Human Genetics Laboratory, Department of Psychiatry and Human Behavior, University of California, Irvine, USA.

²⁰  Malaria Research Laboratory, Karolinska University Hospital, Stockholm, Sweden.

²¹  Department of Molecular Immunogenetics, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.

²²  Departamento de Biologia Molecular, Instituto de Investigaciones en Ciencias de la Salud, Universidad Nacional de Asuncion, Paraguay.

²³  Division of Population Genetics, National Institute of Genetics, Mishima, Japan.

²⁴  Department of Pediatrics, University of Iowa, Iowa City, USA.

²⁵  Laboratory for SNP Analysis, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Tokyo, Japan.

²⁶  Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan.

AC003034AC007728Human earwax consists of wet and dry types. Dry earwax is frequent in East Asians, whereas wet earwax is common in other populations. Here we show that a SNP, 538G A (rs17822931), in the ABCC11 gene is responsible for determination of earwax type. The AA genotype corresponds to dry earwax, and GA and GG to wet type. A 27-bp deletion in ABCC11 exon 29 was also found in a few individuals of Asian ancestry. A functional assay demonstrated that cells with allele A show a lower excretory activity for cGMP than those with allele G. The allele A frequency shows a north-south and east-west downward geographical gradient; worldwide, it is highest in Chinese and Koreans, and a common dry-type haplotype is retained among various ethnic populations. These suggest that the allele A arose in northeast Asia and thereafter spread through the world. The 538G A SNP is the first example of DNA polymorphism determining a visible genetic trait.

	Top