Environmental Health and Preventive Medicine

, Volume 15, Issue 2, pp 94–104

A rare Asian founder polymorphism of Raptor may explain the high prevalence of Moyamoya disease among East Asians and its low prevalence among Caucasians

  • Wanyang Liu
  • Hirokuni Hashikata
  • Kayoko Inoue
  • Norio Matsuura
  • Yohei Mineharu
  • Hatasu Kobayashi
  • Ken-ichiro Kikuta
  • Yasushi Takagi
  • Toshiaki Hitomi
  • Boris Krischek
  • Li-Ping Zou
  • Fang Fang
  • Roman Herzig
  • Jeong-Eun Kim
  • Hyun-Seung Kang
  • Chang-Wan Oh
  • David-Alexandre Tregouet
  • Nobuo Hashimoto
  • Akio Koizumi
Regular Article

Abstract

Background

In an earlier study, we identified a locus for Moyamoya disease (MMD) on 17q25.3.

Methods

Linkage analysis and fine mapping were conducted for two new families in additional to the previously studied 15 families. Three genes, CARD14, Raptor, and AATK, were selected based on key words, namely, “inflammation”, “apoptosis”, “proliferation”, and “vascular system”, for further sequencing. A segregation analysis of 34 pedigrees was performed, followed by a case–control study in Japanese (90 cases vs. 384 controls), Korean (41 cases vs. 223 controls), Chinese (23 cases and 100 controls), and Caucasian (25 cases and 164 controls) populations.

Results

Linkage analysis increased the LOD score from 8.07 to 9.67 on 17q25.3. Fine mapping narrowed the linkage signal to a 2.1-Mb region. Sequencing revealed that only one newly identified polymorphism, ss161110142, which was located at position −1480 from the transcription site of the Raptor gene, was common to all four unrelated sequenced familial affected individuals. ss161110142 was then shown to segregate in the 34 pedigrees studied, resulting in a two-point LOD score of 14.2 (P = 3.89 × 10−8). Its penetrance was estimated to be 74.0%. Among the Asian populations tested (Japanese, Korean, and Chinese), the rare allele was much more frequent in cases (26, 33, and 4%, respectively) than in controls (1, 1, and 0%, respectively) and was associated with an increased odds ratio of 52.2 (95% confidence interval 27.2–100.2) (P = 2.5 × 10−49). This allele was, however, not detected in the Caucasian samples. Its population attributable risk was estimated to be 49% in the Japanese population, 66% in the Korean population, and 9% in the Chinese population.

Conclusion

ss161110142 may confer susceptibility to MMD among East Asian populations.

Keywords

Association studies in genetics Cerebral stroke Childhood stroke Genetic linkage Moyamoya disease 

Supplementary material

12199_2009_116_MOESM1_ESM.doc (1.1 mb)
Supplementary Figure 1 (DOC 1.06 mb)
12199_2009_116_MOESM2_ESM.doc (216 kb)
Supplementary Table 1 (DOC 216 kb)

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Copyright information

© The Japanese Society for Hygiene 2009

Authors and Affiliations

  • Wanyang Liu
    • 1
  • Hirokuni Hashikata
    • 1
    • 2
  • Kayoko Inoue
    • 1
  • Norio Matsuura
    • 1
  • Yohei Mineharu
    • 1
    • 2
  • Hatasu Kobayashi
    • 1
  • Ken-ichiro Kikuta
    • 2
  • Yasushi Takagi
    • 2
  • Toshiaki Hitomi
    • 1
  • Boris Krischek
    • 3
  • Li-Ping Zou
    • 4
  • Fang Fang
    • 5
  • Roman Herzig
    • 6
  • Jeong-Eun Kim
    • 7
  • Hyun-Seung Kang
    • 7
  • Chang-Wan Oh
    • 7
  • David-Alexandre Tregouet
    • 8
  • Nobuo Hashimoto
    • 2
  • Akio Koizumi
    • 1
  1. 1.Department of Health and Environmental SciencesKyoto University Graduate School of MedicineYoshida, Sakyo-kuJapan
  2. 2.Department of NeurosurgeryKyoto University Graduate School of MedicineKyotoJapan
  3. 3.Department of NeurosurgeryUniversity of TübingenTübingenGermany
  4. 4.Department of PediatricsChinese People’s Liberation Army General HospitalBeijingChina
  5. 5.Beijing Children’s HospitalCapital Medical UniversityBeijingChina
  6. 6.Department of Neurology, Stroke Center, Faculty of Medicine and DentistryPalacky University and University HospitalOlomoucCzech Republic
  7. 7.Department of NeurosurgerySeoul National University College of MedicineSeoulKorea
  8. 8.Institut National de la Santé et de la Recherche Médicale (INSERM), UMRS_937Université Pierre et Marie CurieParisFrance

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