[en] BACKGROUND: We aimed to investigate the distribution of selected BCL11A and HMIP polymorphisms (SNP's), and to assess the correlation with HPFH in a cohort of sickle cell patients. METHODS: A preliminary cross-sectional study was conducted in 102 patients. Group 1 was composed of patients with HPFH and Group 2 consisted of patients without HbF. We assessed 8 SNPs previously associated with HPFH in cohorts genetically close to the Congolese population. Observed frequencies were compared to expected frequencies. RESULTS: In the group 1, at rs7606173, the observed frequency for the genotype GG was significantly higher and the genotype GC was significantly lower than their respective expected frequencies. At rs9399137, the observed frequency of the genotype TT was significantly lower than expected. Conversely, the observed frequency of the genotype TC was significantly higher than expected. The observed frequency of the genotype TT at rs11886868 was significantly lower than the expected whereas the frequency of the genotype TC was significantly higher than observed. The lowest HbF level was recorded in patients with genotype CC at rs11886868. CONCLUSION: In this preliminary study, the results demonstrate that alleles of some of the 8 studied SNPs are not randomly distributed among patients with or without HPFH in this cohort.
Hofman K, Rodgers G, Ruffin J, et al. A case for developing North-South partnerships for research in sickle cell disease. Blood. 2005;105:921-923.
Ashley-Koch A, Yang Q, Olney RS. Sickle hemoglobin (HbS) allele and sickle cell disease: a HuGE review. Am J Epidemiol. 2000;151:839-845.
Piel FB, Hay SI, Gupta S, et al. Global burden of sickle cell anaemia in children under five, 2010-2050: modelling based on demographics, excess mortality, and interventions. PLoS Med. 2013;10:e1001484.
Rees DC, Williams TN, Gladwin MT. Sickle-cell disease. Lancet. 2010;376:2018-2031.
Bhagat S, Patra PK, Thakur AS. Fetal haemoglobin and β-globin gene cluster haplotypes among sickle cell patients in Chhattisgarh. J Clin Diagn Res. 2013;7:269-272.
Tshilolo L, Summa V, Gregorj C, et al. Foetal haemoglobin, erythrocytes containing foetal haemoglobin, and hematological features in congolese patients with sickle cell anaemia. Anemia. 2012;2012:105349.
Steinberg MH. Genetic etiologies for phenotypic diversity in sickle cell anemia. ScientificWorldJournal. 2009;9:46-67.
Powars DR, Meiselman HJ, Fisher TC, et al. Beta-S gene cluster haplotypes modulate hematologic and hemorheologic expression in sickle cell anemia. Use in predicting clinical severity. Am J Pediatr Hematol Oncol. 1994;16:55-61.
Ginder GD. Epigenetic regulation of fetal globin gene expression in adult erythroid cells. Transl Res. 2015;165:115-125.
Cardoso GL, Diniz IG, Silva AN, et al. “DNA polymorphisms at BCL11A, HBS1L-MYB and Xmn1-HBG2 site loci associated with fetal hemoglobin levels in sickle cell anemia patients from Northern Brazil. Blood Cells Mol Dis. 2014;53:176-179.
Lettre G, Sankaran VG, Bezerra MA, et al. DNA polymorphisms at the BCL11A, HBS1L-MYB, and beta-globin loci associate with fetal hemoglobin levels and pain crises in sickle cell disease. Proc Natl Acad Sci USA. 2008;105:11869-11874.
Uda M, Galanello R, Sanna S, et al. Genome-wide association study shows BCL11A associated with persistent fetal hemoglobin and amelioration of the phenotype of beta-thalassemia. Proc Natl Acad Sci USA. 2008;105:1620-1625.
Akinsheye I, Alsultan A, Solovieff N, et al. Fetal hemoglobin in sickle cell anemia. Blood. 2011;118:19-27.
Sebastiani P, Farrell JJ, Alsultan A, et al. BCL11A enhancer haplotypes and fetal hemoglobin in sickle cell anemia. Blood Cells Mol Dis. 2015;54:224-230.
Ballas SK. More definitions in sickle cell disease: steady state v base line data. Am J Hematol. 2012;87:338.
Solovieff N, Milton JN, Hartley SW, et al. Fetal hemoglobin in sickle cell anemia: genome-wide association studies suggest a regulatory region in the 5′ olfactory receptor gene cluster. Blood. 2010;115:1815-1822.
Thein SL, Menzel S, Peng X, et al. Intergenic variants of HBS1L-MYB are responsible for a major quantitative trait locus on chromosome 6q23 influencing fetal hemoglobin levels in adults. Proc Natl Acad Sci U S A. 2007;104:11346-11351.
Fanis P, Kousiappa I, Phylactides M, et al. Genotyping of BCL11A and HBS1L-MYB SNPs associated with fetal haemoglobin levels: a SNaPshot minisequencing approach. BMC Genom. 2014;15:108.
Yamsri S, Pakdee N, Fucharoen G, et al. Molecular understanding of non-transfusion-dependent thalassemia associated with hemoglobin E-β-thalassemia in Northeast Thailand. Acta Haematol. 2016;136:233-239.
Rujito L, Basalamah M, Siswandari W, et al. Modifying effect of XmnI, BCL11A, and HBS1L-MYB on clinical appearances: a study on β-thalassemia and hemoglobin E/β-thalassemia patients in Indonesia. Hematol Oncol Stem Cell Ther. 2016;9:55-63.
Pule GD, Ngo Bitoungui VJ, Chetcha Chemegni B, et al. Association between variants at BCL11A erythroid-specific enhancer and fetal hemoglobin levels among sickle cell disease patients in Cameroon: implications for future therapeutic interventions. OMICS. 2015;19:627-631.
Bitoungui VJ, Ngogang J, Wonkam A. Polymorphism at BCL11A compared to HBS1L-MYB loci explains less of the variance in HbF in patients with sickle cell disease in Cameroon. Blood Cells Mol Dis. 2015;54:268-269.
Wonkam A, Ngo Bitoungui VJ, Vorster AA, et al. Association of variants at BCL11A and HBS1L-MYB with hemoglobin F and hospitalization rates among sickle cell patients in Cameroon. PLoS ONE. 2014;9:e92506.
Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988;16:1215.
Bhatnagar P, Purvis S, Barron-Casella E, et al. Genome-wide association study identifies genetic variants influencing F-cell levels in sickle-cell patients. J Hum Genet. 2011;56:316-323.
Milton JN, Gordeuk VR, Taylor JG 6th, Gladwin MT, Steinberg MH, Sebastiani P. Prediction of fetal hemoglobin in sickle cell anemia using an ensemble of genetic risk prediction models. Circ Cardiovasc Genet. 2014;7:110-115.
Wahlberg K, Jiang J, Rooks H, et al. The HBS1L-MYB intergenic interval associated with elevated HbF levels shows characteristics of a distal regulatory region in erythroid cells. Blood. 2009;114:1254-1262.
Farrell JJ, Sherva RM, Chen ZY, et al. A 3-bp deletion in the HBS1L-MYB intergenic region on chromosome 6q23 is associated with HbF expression. Blood. 2011;117:4935-4945.
Mtatiro SN, Singh T, Rooks H, et al. Genome wide association study of fetal hemoglobin in sickle cell anemia in Tanzania. PLoS ONE. 2014;9:e111464. eCollection 2014.
Makani J, Menzel S, Nkya S, et al. Genetics of fetal hemoglobin in Tanzanian and British patients with sickle cell anemia. Blood. 2011;117:1390-1392.
