Letter | Published:

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

Nature Genetics 38, 324–330 (2006) | Download Citation

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Abstract

Human 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.

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GenBank/EMBL/DDBJ

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Acknowledgements

We are grateful to all volunteers, especially to Nagasaki University Administration Officers, for their participation in this study and are grateful to S. Horai, P. Duanchang, S. Pookajorn, A. Soemantri, W. Settheetham-Ishida, P.G. Babu, R. Kimura, P.N. Tongol-Rivera, K. Tajim, L.H. Sulaiman and K. Na-Bangchang for assistance in collecting samples. We also thank N. Yanai and Y. Noguchi for their technical assistance and S.M. Kennedy for correction of the manuscript. This study was supported in part by CREST from the Japan Science and Technology Agency (JST) and Grants-in-Aid for Scientific Research (Category S, No. 13854024; Priority Area 'Applied Genomics' No. 17019055; Category C, No. 17590288) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

Author information

Affiliations

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

    • Koh-ichiro Yoshiura
    • , Akira Kinoshita
    • , Mitsuko Nakashima
    • , Nadiya Sosonkina
    • , Christophe K Mapendano
    • , Mohsen Ghadami
    • , Masayo Nomura
    • , Nobutomo Miwa
    •  & Norio Niikawa

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

    • Koh-ichiro Yoshiura
    • , Akira Kinoshita
    • , Tadashi Kaname
    • , Mitsuko Nakashima
    • , Nadiya Sosonkina
    • , Christophe K Mapendano
    • , Mohsen Ghadami
    • , Masayo Nomura
    • , De-Sheng Liang
    • , Nobutomo Miwa
    • , Tohru Ohta
    •  & Norio Niikawa

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

    • Takafumi Ishida
    •  & Aya Ninokata

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

    • Toshihisa Ishikawa

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

    • Tadashi Kaname

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

    • Makoto Bannai
    •  & Katsushi Tokunaga

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

    • Shunro Sonoda

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

    • Ryoichi Komaki

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

    • Makoto Ihara

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

    • Vladimir A Saenko

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

    • Gabit K Alipov
    •  & Ichiro Sekine

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

    • Kazuki Komatsu
    •  & Haruo Takahashi

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

    • Mitsuko Nakashima

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

    • Masayo Nomura

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

    • De-Sheng Liang

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

    • Dae-Kwang Kim

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

    • Ariuntuul Garidkhuu
    •  & Nagato Natsume

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

    • Tohru Ohta

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

    • Hiroaki Tomita

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

    • Akira Kaneko

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

    • Mihoko Kikuchi
    •  & Kenji Hirayama

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

    • Graciela Russomando

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

    • Minaka Ishibashi
    • , Aya Takahashi
    •  & Naruya Saitou

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

    • Jeffery C Murray

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

    • Susumu Saito
    •  & Yusuke Nakamura

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

    • Yusuke Nakamura

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The authors declare no competing financial interests.

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Correspondence to Koh-ichiro Yoshiura.

Supplementary information

PDF files

  1. 1.

    Supplementary Table 1

    Three-locus genotypes of 118 and 126 Japanese whose earwax types were self-declared and diagnosed otologically, and who underwent the first- and second-step association analyses, respectively.

  2. 2.

    Supplementary Table 2

    Genotypes at the rs17822931 site and frequencies of alleles “A” and Δ27 in ABCC11 and of dry cerumen among different human populations.

  3. 3.

    Supplementary Table 3

    Inferred haplotypes' frequencies at three polymorphic loci (rs17822931-rs6500380-ss49784070) in the Japanese (Nagasaki inhabitants), Southern Han Chinese (Changsha inhabitants), Native Americans, Native Bolivians, and the CEPH families of European origin.

  4. 4.

    Supplementary Table 4

    Primer sequences for 24 SNPs that were used for haplotyping in a 600-kb interval and its flanking region.

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DOI

https://doi.org/10.1038/ng1733

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