The Impact of XmnI-HBG2, BCL11A and HBS1L-MYB Single Nucleotide Polymorphisms on Hb F Variation of Hematologically Normal Iranian Individuals.
The impact of Hb F on severity of sickle cell disease and β-thalassemia (β-thal) is well documented. The XmnI-HBG2, BCL11A and HBS1L-MYB single nucleotide polymorphisms (SNPs) have been introduced as the most important factors causing variation in fetal hemoglobin (Hb F) levels in different population studies. However, the extent of their effect could be population-specific. In this study, multivariate linear regression analysis was used to evaluate the association of Hb F with age, sex, and eight SNPs, including XmnI-HBG2, four BCL11A, two HBS1L-MYB SNPs and the polymorphic palindromic 5' hypersensitive 4-locus control region (5'HS4-LCR). One hundred and twenty-two hematologically normal individuals, from a previous study cohort, constituted our study population. In multivariate regression analyses, no association of Hb F was observed with age or sex of the individuals and SNPs in this study. We conducted a univariate regression analysis to further investigate the results, which among all the factors only detected XmnI-HBG2 and 5'HS4 SNPs as significant modifiers of Hb F. The significance of these two factors disappeared in a bivariate analysis. These results suggest that either XmnI-HBG2 or 5'HS4-LCR have a stronger contribution in Hb F variations of the Iranian population than BCL11A and HBS1L-MYB SNPs. Furthermore, the effect of low population size and technical limitations on obtained results could not be ruled out.
a Genetics Research Center, University of Social Welfare and Rehabilitation Sciences , Tehran , Iran.
Elaheh
E
Keyhani
a Genetics Research Center, University of Social Welfare and Rehabilitation Sciences , Tehran , Iran.
Mahjoobeh
M
Jafari Vesiehsari
a Genetics Research Center, University of Social Welfare and Rehabilitation Sciences , Tehran , Iran.
Setareh
S
Talebi Kakroodi
b Department of Medical Genetics , School of Medicine, International Campus , Tehran , Iran.
Elham
E
Darabi
a Genetics Research Center, University of Social Welfare and Rehabilitation Sciences , Tehran , Iran.
Fahimeh
F
Zamani
c Department of Biostatistics and Computer Sciences , University of Social Welfare and Rehabilitation Sciences , Tehran , Iran.
Masoud
M
Karimlou
d Department of Public Health , School of Public Health, Zanjan University of Medical Sciences , Zanjan , Iran.
Koorosh
K
Kamali
a Genetics Research Center, University of Social Welfare and Rehabilitation Sciences , Tehran , Iran.
Maryam
M
Neishabury
D000367:Age Factors; D002352:Carrier Proteins / Q000235:genetics; D005260:Female; D005319:Fetal Hemoglobin / Q000032:analysis / Q000235:genetics*; D060045:Genes, Modifier; D014644:Genetic Variation; D006801:Humans; D007492:Iran / Q000453:epidemiology; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012044:Regression Analysis; D012097:Repressor Proteins; D012737:Sex Factors
C486563:BCL11A protein, human; D002352:Carrier Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; D005319:Fetal Hemoglobin
5′ hypersensitive 4-locus control region (5′HS4-LCR); BCL11A; HBS1L-MYB; Hb F; Thalassemia; XmnI