Human Genetics

, Volume 132, Issue 2, pp 201–217 | Cite as

Positive natural selection of TRIB2, a novel gene that influences visceral fat accumulation, in East Asia

  • Kazuhiro NakayamaEmail author
  • Ayumi Ogawa
  • Hiroshi Miyashita
  • Yasuharu Tabara
  • Michiya Igase
  • Katsuhiko Kohara
  • Tetsuro Miki
  • Yasuo Kagawa
  • Yoshiko Yanagisawa
  • Mitsuhiro Katashima
  • Tomohiro Onda
  • Koichi Okada
  • Shogo Fukushima
  • Sadahiko IwamotoEmail author
Original Investigation


Accumulation of visceral fat increases cardiovascular mortality in industrialized societies. However, during the evolution of the modern human, visceral fat may have acted as energy storage facility to survive in times of famine. Therefore, past natural selection might contribute to shaping the variation of visceral fat accumulation in present populations. Here, we report that the gene encoding tribbles homolog 2 (TRIB2) influenced visceral fat accumulation and was operated by recent positive natural selection in East Asians. Our candidate gene association analysis on 11 metabolic traits of 5,810 East Asians revealed that rs1057001, a T/A transversion polymorphism in 3′untranslated region (UTR) of TRIB2, was strongly associated with visceral fat area (VFA) and waist circumference adjusted for body mass index (P = 2.7 × 10−6 and P = 9.0 × 10−6, respectively). rs1057001 was in absolute linkage disequilibrium with a conserved insertion-deletion polymorphism in the 3′UTR and was associated with allelic imbalance of TRIB2 transcript levels in adipose tissues. rs1057001 showed high degree of interpopulation variation of the allele frequency; the low-VFA-associated A allele was found with high frequencies in East Asians. Haplotypes containing the rs1057001 A allele exhibited a signature of a selective sweep, which may have occurred 16,546–27,827 years ago in East Asians. Given the predominance of the thrifty gene hypothesis, it is surprising that the apparently non-thrifty allele was selectively favored in the evolution of modern humans. Environmental/physiological factors other than famine would be needed to explain the non-neutral evolution of TRIB2 in East Asians.


Modern Human High Resolution Melting Selective Sweep Allelic Imbalance Extend Haplotype Homozygosity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We would like to thank our colleagues at the Division of Human Genetics, Jichi Medical University. We are also grateful the staff of the Jichi Medical University Hospital Health Checkup Center for their cooperation in the collection of samples from Japanese individuals. We would like to thank Editage for providing editorial assistance. This study was supported in part by a KAKENHI Grant-in-Aid for young researchers (A) [23687036 to K.N.], a Grant-in Aid for Basic Science (C) [22591001 to S.I.] from the Ministry of Education, Culture, Sports, Science and Technology of Japan, a grant from the Kao Research Council for the Study of Healthcare Science (KN), and JKA through its promotion funds from KEIRIN RACE.

Conflict of interest

Y.Y., M.K., and T.O. are employees of the Kao Corporation. K.O. is an employee of the Panasonic Corporation. S.F. is an employee of the Panasonic Healthcare Co., Ltd.

Supplementary material

439_2012_1240_MOESM1_ESM.pdf (476 kb)
Supplementary material 1 (PDF 477 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Kazuhiro Nakayama
    • 1
    Email author
  • Ayumi Ogawa
    • 1
  • Hiroshi Miyashita
    • 2
  • Yasuharu Tabara
    • 3
  • Michiya Igase
    • 4
  • Katsuhiko Kohara
    • 4
  • Tetsuro Miki
    • 4
  • Yasuo Kagawa
    • 5
  • Yoshiko Yanagisawa
    • 1
    • 6
  • Mitsuhiro Katashima
    • 6
  • Tomohiro Onda
    • 7
  • Koichi Okada
    • 8
  • Shogo Fukushima
    • 9
  • Sadahiko Iwamoto
    • 1
    Email author
  1. 1.Division of Human Genetics, Center for Molecular MedicineJichi Medical UniversityShimotsukeJapan
  2. 2.Jichi Medical University HospitalJichi Medical UniversityShimotsukeJapan
  3. 3.Center for Genomic MedicineKyoto University Graduate School of MedicineKyotoJapan
  4. 4.Department of Geriatric MedicineEhime University Graduate School of MedicineToonJapan
  5. 5.High Technology Research CenterKagawa Nutrition UniversitySakadoJapan
  6. 6.Health Care Food ResearchHuman Health Care Research, Research and Development, Kao CorporationTokyoJapan
  7. 7.Processing Development ResearchResearch and Development, Kao CorporationTokyoJapan
  8. 8.Appliances Company Corporate Engineering DivisionPanasonic CorporationKusatsuJapan
  9. 9.Corporate Research and Development CenterPanasonic Healthcare Co., LtdKodamaJapan

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