Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

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


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.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Prices vary by article type



Prices may be subject to local taxes which are calculated during checkout

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.

Accession codes




  1. Adachi, B. Das Ohrenschmalz als Rassenmerkmal und der Rassengeruch ('Achselgeruch') nebst dem Rassenunterschied der Schweissdrüsen. Z Rassenk 6, 273–307 (1937).

    Google Scholar 

  2. Matsunaga, E. The dimorphism in human normal cerumen. Ann. Hum. Genet. 25, 273–286 (1962).

    Article  CAS  Google Scholar 

  3. Petrakis, N.L., Molohon, K.T. & Tepper, D.J. Cerumen in American Indians: Genetic implications of sticky and dry types. Science 158, 1992–1993 (1967).

    Article  Google Scholar 

  4. Omoto, K. Polymorphic traits in peoples of eastern Asia and the Pacific. Isr. J. Med. Sci. 9, 1195–1215 (1973).

    CAS  PubMed  Google Scholar 

  5. Petrakis, N.L., Pingke, U., Petrakis, S.J. & Petrakis, S.L. Evidence for a genetic cline in earwax type in the Middle East and Southeast Asia. Am. J. Phys. Anthropol. 35, 141–144 (1971).

    Article  CAS  Google Scholar 

  6. Petrakis, N.L. Cerumen genetics and human breast cancer. Science 173, 347–349 (1971).

    Article  CAS  Google Scholar 

  7. Ing, R., Petrakis, L. & Ho, H.C. Evidence against association between wet cerumen and breast cancer. Lancet 1, 41 (1973).

    Article  CAS  Google Scholar 

  8. Tomita, H.-a. et al. Mapping of the wet/dry earwax locus to the pericentromeric region of chromosome 16. Lancet 359, 2000–2002 (2002).

    Article  CAS  Google Scholar 

  9. Yabuuchi, H., Shimizu, H., Takayanagi, S. & Ishikawa, T. Multiple splicing variants of two new human ATP-binding cassette transporters, ABCC11 and ABCC12. Biochem. Biophys. Res. Commun. 288, 933–939 (2001).

    Article  CAS  Google Scholar 

  10. Tammur, J. et al. Two new genes from the human ATP-binding cassette transporter superfamily, ABCC11 and ABCC12, tandemly duplicated on chromosome 16q12. Gene 273, 89–96 (2001).

    Article  CAS  Google Scholar 

  11. Bera, T.K., Lee, S., Salvatore, G., Lee, B. & Pastan, I. MRP8, a new member of ABC transporter superfamily, identified by EST database mining and gene prediction program, is highly expressed in breast cancer. Mol. Med. 7, 509–516 (2001).

    Article  CAS  Google Scholar 

  12. Guo, Y. et al. MRP8, ATP-binding cassette C11 (ABCC11), is a cyclic nucleotide efflux pump and a resistance factor for fluoropyrimidines 2′,3′-dideoxycytidine and 9′-(2′-phosphonylmethoxyethyl) adenine. J. Biol. Chem. 278, 29509–29514 (2003).

    Article  CAS  Google Scholar 

  13. Chen, Z.S., Guo, Y., Belinsky, M.G., Kotova, E. & Kruh, G.D. Transport of bile acids, sulfated steroids, estradiol 17-beta-D-glucuronide, and leukotriene C4 by human multidrug resistance protein 8 (ABCC11). Mol. Pharmacol. 67, 545–557 (2005).

    Article  CAS  Google Scholar 

  14. Burkhart, C.N., Kruge, M.A., Burkhart, C.G. & Black, C. Cerumen composition by flash pyrolysis-gas chromatography/mass spectrometry. Otol. Neurotol. 22, 715–722 (2001).

    Article  CAS  Google Scholar 

  15. Shugyo, Y. et al. Morphological differences between secretory cells of wet and dry type of human ceruminous glands. Am. J. Anat. 181, 377–384 (1988).

    Article  CAS  Google Scholar 

  16. Shulenin, S., Nogee, L.M., Annilo, T., Wert, S.E., Whitsett, J.A. & Dean, M. ABCA3 gene mutations in newborns with fatal surfactant deficiency. N. Engl. J. Med. 350, 1296–1303 (2005).

    Article  Google Scholar 

  17. Diller, K.C., Gilbert, W.A. & Kocher, T.D. Selective sweeps in the human genome: A starting point for identifying genetic differences between modern human and chimpanzees. Mol. Biol. Evol. 19, 2342–2345 (2002).

    Article  CAS  Google Scholar 

  18. The International HapMap Consortium. A haplotype map of the human genome. Nature 437, 1299–1320 (2005).

  19. Bonatto, S.L. & Salzano, F.M. A single and early migration for the peopling of the Americas supported by mitochondrial DNA sequence data. Proc. Natl. Acad. Sci. USA 94, 1866–1871 (1997).

    Article  CAS  Google Scholar 

  20. Tokunaga, K., Ohashi, J., Bannai, M. & Juji, T. Genetic link between Asians and native Americans: Evidence from HLA genes and haplotypes. Hum. Immunol. 62, 1001–1008 (2001).

    Article  CAS  Google Scholar 

  21. Dillehay, T.D. Tracking the first Americans. Nature 425, 23–24 (2003).

    Article  CAS  Google Scholar 

  22. Bang, Y.H. et al. Histopathology of apocrine bromhidrosis. Plast. Reconstr. Surg. 98, 288–292 (1996).

    Article  CAS  Google Scholar 

  23. Shimizu, H. et al. Characterization of the mouse Abcc12 gene and its transcript encoding an ATP-binding cassette transporter, an orthologue of human ABCC12. Gene 310, 17–28 (2003).

    Article  CAS  Google Scholar 

  24. Yamasaki, K., Singer, A. & Beauchamp, G.K. Origin, functions and chemistry of H-2 regulated odorants. Genetica 104, 235–240 (1999).

    Article  Google Scholar 

  25. Barrett, J.C., Fry, B., Maller, J. & Daly, M.J. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21, 263–265 (2005).

    Article  CAS  Google Scholar 

  26. Masuzaki, H. et al. Detection of cell free placental DNA in maternal plasma: direct evidence from three cases of confined placental mosaicism. J. Med. Genet. 41, 289–292 (2004).

    Article  CAS  Google Scholar 

  27. Mitomo, H. et al. A functional study on polymorphism of the ATP-binding cassette transporter ABCG12: Critical role of arginine-482 in methotrexate transport. Biochem. J. 373, 767–774 (2003).

    Article  CAS  Google Scholar 

  28. Ishikawa, T. et al. High-speed screening of human ABC transporter function and genetic polymorphisms: New strategies in pharmacogenomics. Methods Enzymol. 400, 485–510 (2005).

    Article  CAS  Google Scholar 

Download references


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


Corresponding author

Correspondence to Koh-ichiro Yoshiura.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

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)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

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).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing