Association of ZBTB38 gene polymorphism (rs724016) with height and fetal hemoglobin in individuals with sickle cell anemia

Objectives

Our study evaluated the association of the polymorphism rs724016 in the ZBTB38 gene, previously associated with height in other populations, with predictors of height, clinical outcomes, and laboratory parameters in sickle cell anemia (SCA).

Methods

Cross-sectional study with individuals with SCA and aged between 3 and 20 years. Clinical, laboratory, molecular, and bone age (BA) data were evaluated. Levels of IGF-1 and IGFBP-3 were adjusted for BA, target height (TH) was calculated as the mean parental height standard deviation score (SDS), and predicted adult height (PAH) SDS was calculated using BA.

Results

We evaluated 80 individuals with SCA. The homozygous genotype of the G allele of rs724016 was associated with a lower height SDS (p < 0.001) and, in a additive genetic model, was negatively associated with HbF levels (p = 0.016). Lower adjusted IGF-1 levels were associated with co-inheritance of alpha-thalassemia and with the absence of HU therapy. Elevated HbF levels were associated with a lower deficit in adjusted growth potential (TH minus PAH).

Conclusion

Our analysis shows that SNP rs724016 in the ZBTB38 is associated with shorter height and lower HbF levels, an important modifier of SCA.