Hb F Levels in beta-Thalassemia Carriers and Normal Individuals: Known and Unknown Quantitative Trait Loci in the beta-Globin Gene Cluster

• Type: Article in International Scientific Journal
• Date: 2022

Authors

Manco, L (Author) Other; Santos, R (Author) Other; Rocha, C (Author) Other; Relvas, L (Author) Other; Bento, C (Author) Other; Maia, T (Author) Other; Gomes, V (Author) Other; Amorim, A (Author) FCUP; Prata, MJ (Author) FCUP

Journal

Title: Hemoglobin

Vol. 46

Pages: 168-175

ISSN: 0363-0269

Publisher: Taylor & Francis

Indexing

ISI Web of Knowledge - 0 Citations

Other information

Authenticus ID: P-00W-KNC

DOI: 10.1080/03630269.2022.2070498

Abstract (EN): In the already identified quantitative trait loci (QTL), modulating Hb F levels are cis-acting haplotypes of the beta-globin gene cluster itself, although the single nucleotide polymorphisms (SNPs) accounting more for the association, remain uncertain. In this study, the role in Hb F production of previously reported candidate SNPs within the beta-globin gene cluster was reexamined, along with a yet poorly studied variation in the BGLT3 gene. In a sample of beta-thalassemia (beta-thal) carriers, we succeeded in replicating the significant association between increased Hb F levels and rs7482144 (C>T) (HBG2 XmnI), which is the most well-established variation in the cluster influencing the trait. This SNP was found to be in strong linkage disequilibrium (LD) with a variation in the HBBP1 gene [rs10128556 (G>A)], which consistently revealed a similar association signal. Remarkably, much stronger than the latter associations were those involving both rs968857 (T allele) (3' HBBP1) and rs7924684 (G allele) (BGLT3), two SNPs that were also in strong LD. As the pattern of LD detected in the beta-globin gene cluster does not correlate with a tight linkage between markers, complex interactions between SNPs at the cluster seem to modulate Hb F. Seeing that no such associations were detected in normal subjects, the question can be raised on whether, under erythropoiesis stress, epigenetic mechanisms contribute to change the regulation of the entire beta-globin gene cluster. In conclusion, we provide statistical evidence for a new player within the beta-globin gene cluster, BGLT3, that in cooperation with other regions influences Hb F levels in beta-thal carriers.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8