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

Nature Genetics volume 38, pages 324–330 (2006)Cite this article

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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Figure 1: Four genes, ABCC12, ABCC11, LONPL and SIAH1, and 31 polymorphic DNA markers located in the ∼600-kb region between B81540 and IMS-JST141676.
Figure 2: Linkage disequilibrium (LD) analysis of candidate region.
Figure 3: Pedigree analysis of an individual showing phenotype-genotype discrepancy (at rs17822931).
Figure 4: Worldwide frequency of allele A (open portion in each circle).
Figure 5: ABCC11 expression and cGMP transport in LLC-PK1 cells transfected with allele A and those with allele G.

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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

Authors and 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. Department of Psychiatry and Human Behavior, Human Genetics Laboratory, 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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  1. Koh-ichiro Yoshiura
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Correspondence to Koh-ichiro Yoshiura.

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Supplementary information

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. (PDF 47 kb)

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. (PDF 78 kb)

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. (PDF 51 kb)

Supplementary Table 4

Primer sequences for 24 SNPs that were used for haplotyping in a 600-kb interval and its flanking region. (PDF 64 kb)

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Yoshiura, Ki., Kinoshita, A., Ishida, T. et al. A SNP in the ABCC11 gene is the determinant of human earwax type. Nat Genet 38, 324–330 (2006). https://doi.org/10.1038/ng1733

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