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Journal of Clinical Immunology

, Volume 30, Issue 1, pp 132–137 | Cite as

BAK, BAX, and NBK/BIK Proapoptotic Gene Alterations in Iranian Patients with Ataxia Telangiectasia

  • Anna Isaian
  • Natalia V. Bogdanova
  • Masoud Houshmand
  • Masoud Movahadi
  • Asghar Agamohammadi
  • Nima Rezaei
  • Lida Atarod
  • Mahnaz Sadeghi-Shabestari
  • Seyed Hasan Tonekaboni
  • Zahra Chavoshzadeh
  • Seyed Mohammad Seyed Hassani
  • Reza Mirfakhrai
  • Taher Cheraghi
  • Najmoddin Kalantari
  • Mitra Ataei
  • Thilo Dork-Bousset
  • Mohammad Hossein Sanati
Article

Abstract

Introduction

Ataxia telangiectasia (AT) is an autosomal recessive multisystem disorder characterized by variable immunodeficiency, progressive neurodegeneration, occulocutaneous telangiectasia, and an increased susceptibility to malignancies. This study was designed to study the role of proapoptotic BAK, BAX, and NBK/BIK genes in a group of patients with AT to elucidate the possible role of these genes in progression of malignancies in this disease.

Materials and Methods

Fifty Iranian patients with AT were investigated in this study. The entire coding regions of the BAK gene (exons 2–6), NBK/BIK gene (exons 2–5), and BAX gene (exons 1–7) were amplified using polymerase chain reaction (PCR). The PCR products were separated by 2% agarose gel electrophoresis, and all positive samples were verified by direct sequencing of PCR products using the same primers used for PCR amplification, BigDye chemistry, and Avent 3100 Genetic Analyzer following the manufacturer’s instructions (Applied Biosystems).

Results

Eight of fifty Iranian AT patients (16%) exhibited a C > T transition in exon 2 (c342C > T) of the BAK gene, while none of the healthy controls had such alteration (P = 0.0001). Higher frequency of another nucleotide substitution in the noncoding region of exon 7 in BAX gene (6855G > A) was also identified in 68% of the patient group versus 24% in the controls (P < 0.0001). Sequence alteration in intronic region of the NBK/BIK gene IVS4-12delTC was observed in 52% of AT patients, which was significantly higher than 20% in the control group (P = 0.0023). Another variant IVS1146C > T in the intronic region of the BAX gene was found in 78% of patients, which was significantly higher than 10% in the controls (P < 0.0001). Frequency of alteration in intronic region of exon 3 of the BAX gene (IVS3 + 14A > G) was also significantly higher in the AT patients (P < 0.0001).

Discussion

Several alterations in the proapoptotic genes BAK, NBK/BIK, and BAX were found in our study, which could elucidate involvement of the mitochondrial pathway mediated apoptosis in accelerating and developing of cancers and in immunopathogenesis of AT. Such altered apoptosis in AT could play some roles in developing cancers in this group of patients.

Keywords

Ataxia telangiectasia BAK BAX NBK/BIK cancer polymorphisms 

Notes

Acknowledgment

The authors are very grateful for all colleagues in Medical School of Hannover (Hannover, Germany) for their kind help and advices in the laboratory, and all the patients and their families for their kind collaboration in this study. We would like to thank Dr. Ali Rabbani for his help and support.

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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Anna Isaian
    • 1
    • 2
    • 3
  • Natalia V. Bogdanova
    • 3
  • Masoud Houshmand
    • 1
  • Masoud Movahadi
    • 2
  • Asghar Agamohammadi
    • 2
    • 4
  • Nima Rezaei
    • 2
    • 4
  • Lida Atarod
    • 2
  • Mahnaz Sadeghi-Shabestari
    • 5
  • Seyed Hasan Tonekaboni
    • 6
  • Zahra Chavoshzadeh
    • 6
  • Seyed Mohammad Seyed Hassani
    • 1
  • Reza Mirfakhrai
    • 1
  • Taher Cheraghi
    • 2
  • Najmoddin Kalantari
    • 2
  • Mitra Ataei
    • 1
  • Thilo Dork-Bousset
    • 3
  • Mohammad Hossein Sanati
    • 1
  1. 1.National Institute of Genetic Engineering and BiotechnologyTehranIran
  2. 2.Department of Pediatrics, Pediatrics Center of Excellence, Children’s Medical CenterTehran University of Medical SciencesTehranIran
  3. 3.Gynaecology Research UnitMedical School of HannoverHannoverGermany
  4. 4.Growth and Development Research CenterTehran University of Medical SciencesTehranIran
  5. 5.Division of Pediatric Immunology and Allergy, Children’s HospitalTabriz University (Medical Sciences)TabrizIran
  6. 6.Mofid Children HospitalShaheed Beheshti UniversityTehranIran

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