Amelioration of Sardinian beta0 thalassemia by genetic modifiers - PubMed
- ️Thu Jan 01 2009
Amelioration of Sardinian beta0 thalassemia by genetic modifiers
Renzo Galanello et al. Blood. 2009.
Abstract
Sardinian beta-thalassemia patients all are homozygotes for the same null allele in the beta-globin gene, but the clinical manifestations are extremely variable in severity. Previous studies have shown that the coinheritance of alpha-thalassemia or the presence of genetic variants that sustain fetal hemoglobin production has a strong impact on ameliorating the clinical phenotype. Here we evaluate the contribution of variants in the BCL11A, and HBS1L-MYB genes, implicated in the regulation of fetal hemoglobin, and of alpha-thalassemia coinheritance in 50 thalassemia intermedia and 75 thalassemia major patients. We confirm that alpha-thalassemia and allele C of single nucleotide polymorphism rs-11886868 in BCL11A were selectively represented in thalassemia intermedia patients. Moreover, allele G at single nucleotide polymorphism rs9389268 in the HBS1L-MYB locus was significantly more frequent in the thalassemia intermedia patients. This trio of genetic factors can account for 75% of the variation differences in phenotype severity.
Figures

Proportion of patients and number of ameliorating alleles in the 2 groups. The figure shows the proportion of thalassemia major and thalassemia intermedia patients carrying 0, 1, or more of the alleles considered to be responsible for the amelioration of the clinical expression of the phenotype (positive alleles). Persons carrying more than 4 positive alleles were not observed.
Similar articles
-
Lai Y, Chen Y, Chen B, Zheng H, Yi S, Li G, Wei H, He S, Zheng C. Lai Y, et al. Hemoglobin. 2016 Nov;40(6):405-410. doi: 10.1080/03630269.2016.1253586. Hemoglobin. 2016. PMID: 28361591
-
Buccheri MA, Spina S, Ruberto C, Lombardo T, Labie D, Ragusa AA. Buccheri MA, et al. Hemoglobin. 2013;37(5):423-34. doi: 10.3109/03630269.2013.800823. Epub 2013 Jun 19. Hemoglobin. 2013. PMID: 23777413
-
Bashir S, Mahmood S, Mohsin S, Tabassum I, Ghafoor M, Sajjad O. Bashir S, et al. J Pak Med Assoc. 2021 May;71(5):1394-1398. doi: 10.47391/JPMA.1351. J Pak Med Assoc. 2021. PMID: 34091621
-
[Progress on genes related to fetal hemoglobin quantitative trait].
Guo XQ. Guo XQ. Yi Chuan. 2010 Apr;32(4):295-300. doi: 10.3724/sp.j.1005.2010.00295. Yi Chuan. 2010. PMID: 20423883 Review. Chinese.
-
Bauer DE, Orkin SH. Bauer DE, et al. Curr Opin Genet Dev. 2015 Aug;33:62-70. doi: 10.1016/j.gde.2015.08.001. Epub 2015 Sep 14. Curr Opin Genet Dev. 2015. PMID: 26375765 Free PMC article. Review.
Cited by
-
Frequency of secondary modifiers in Beta Thalassemia intermedia in patients from Northern Punjab.
Nasreen F, Khalid A, Zafar L, Ahmad S, Shaikh A. Nasreen F, et al. Pak J Med Sci. 2023 Sep-Oct;39(5):1517-1520. doi: 10.12669/pjms.39.5.7376. Pak J Med Sci. 2023. PMID: 37680845 Free PMC article.
-
Fetal globin gene repressors as drug targets for molecular therapies to treat the β-globinopathies.
Suzuki M, Yamamoto M, Engel JD. Suzuki M, et al. Mol Cell Biol. 2014 Oct 1;34(19):3560-9. doi: 10.1128/MCB.00714-14. Epub 2014 Jul 14. Mol Cell Biol. 2014. PMID: 25022757 Free PMC article. Review.
-
Dadheech S, Jain S, Madhulatha D, Sharma V, Joseph J, Jyothy A, Munshi A. Dadheech S, et al. Mol Biol Rep. 2014 May;41(5):3331-7. doi: 10.1007/s11033-014-3195-5. Epub 2014 Feb 2. Mol Biol Rep. 2014. PMID: 24488321
-
Xmn1-158 γGVariant in B-Thalassemia Intermediate Patients in South-East of Iran.
Miri-Moghaddam E, Bahrami S, Naderi M, Bazi A, Karimipoor M. Miri-Moghaddam E, et al. Int J Hematol Oncol Stem Cell Res. 2017 Apr 1;11(2):165-171. Int J Hematol Oncol Stem Cell Res. 2017. PMID: 28875012 Free PMC article.
References
-
- Cao A, Galanello R, Rosatelli MC. Genotype-phenotype correlations in β-thalassemias. Blood Rev. 1994;8(1):1–12. - PubMed
-
- Thein SL. Genetic modifiers of β-thalassemia. Haematologica. 2005;90(5):649–660. - PubMed
-
- Menzel S, Garner C, Gut I, et al. A QTL influencing F cell production maps to a gene encoding a zinc-finger protein on chromosome 2p15. Nat Genet. 2007;39(10):1197–1199. - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources