Publication: A genome-wide association identified the common genetic variants influence disease severity in β0-thalassemia/hemoglobin e
Issued Date
2010-01-01
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ISSN
14321203
03406717
03406717
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2-s2.0-77949274495
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Mahidol University
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SCOPUS
Bibliographic Citation
Human Genetics. Vol.127, No.3 (2010), 303-314
Suggested Citation
Manit Nuinoon, Wattanan Makarasara, Taisei Mushiroda, Iswari Setianingsih, Pustika Amalia Wahidiyat, Orapan Sripichai, Natsuhiko Kumasaka, Atsushi Takahashi, Saovaros Svasti, Thongperm Munkongdee, Surakameth Mahasirimongkol, Chayanon Peerapittayamongkol, Vip Viprakasit, Naoyuki Kamatani, Pranee Winichagoon, Michiaki Kubo, Yusuke Nakamura, Suthat Fucharoen A genome-wide association identified the common genetic variants influence disease severity in β0-thalassemia/hemoglobin e. Human Genetics. Vol.127, No.3 (2010), 303-314. doi:10.1007/s00439-009-0770-2 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/28852
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Title
A genome-wide association identified the common genetic variants influence disease severity in β0-thalassemia/hemoglobin e
Author(s)
Manit Nuinoon
Wattanan Makarasara
Taisei Mushiroda
Iswari Setianingsih
Pustika Amalia Wahidiyat
Orapan Sripichai
Natsuhiko Kumasaka
Atsushi Takahashi
Saovaros Svasti
Thongperm Munkongdee
Surakameth Mahasirimongkol
Chayanon Peerapittayamongkol
Vip Viprakasit
Naoyuki Kamatani
Pranee Winichagoon
Michiaki Kubo
Yusuke Nakamura
Suthat Fucharoen
Wattanan Makarasara
Taisei Mushiroda
Iswari Setianingsih
Pustika Amalia Wahidiyat
Orapan Sripichai
Natsuhiko Kumasaka
Atsushi Takahashi
Saovaros Svasti
Thongperm Munkongdee
Surakameth Mahasirimongkol
Chayanon Peerapittayamongkol
Vip Viprakasit
Naoyuki Kamatani
Pranee Winichagoon
Michiaki Kubo
Yusuke Nakamura
Suthat Fucharoen
Abstract
β-Thalassemia/HbE disease is clinically variable. In searching for genetic factors modifying the disease severity, patients were selected based on their disease severities, and a genome-wide association study (GWAS) was performed. Genotyping was conducted with the Illumina Human 610-Quad BeadChips array using DNAs from 618 Thai β0-thalassemia/HbE patients who were classified as 383 severe and 235 mild phenotypes by a validated scoring system. Twenty-three SNPs in three independent genes/regions were identified as being significantly associated with the disease severity. The highest association was observed with SNPs in the β-globin gene cluster (chr.11p15), and rs2071348 of the HBBP1 gene revealed the most significant association [P = 2.96 × 10-13, odds ratio (OR) = 4.33 (95% confidence interval (CI), 2.74-6.84)]. The second was identified in the intergenic region between the HBS1L and MYB genes (chr.6q23), among which rs9376092 was the most significant [P = 2.36 × 10-10, OR = 3.07 (95% CI, 2.16-4.38)]. The third region was located in the BCL11A gene (chr.2p16.1), and rs766432 showed the most significant association [P = 5.87 × 10-10, OR = 3.06 (95% CI, 2.15-4.37)]. All three loci were replicated in an independent cohort of 174 Indonesian patients. The associations to fetal hemoglobin levels were also observed with SNPs on these three regions. Our data indicate that several genetic loci act in concert to influence HbF levels of β0-thalassemia/HbE patients. This study revealed that all the three reported loci and the α-globin gene locus are the best and common predictors of the disease severity in β-thalassemia. © 2009 Springer-Verlag.