Protective BCL11A and HBS1L-MYB polymorphisms in a cohort of 102 Congolese patients suffering from sickle cell anemia (original) (raw)
Related papers
Blood cells, molecules & diseases, 2014
Increased levels of fetal hemoglobin (HbF, α2γ2) may reduce sickle cell anemia severity due to its ability to inhibit HbS polymerization and also reduce the mean corpuscular HbS concentration. We have investigated the influence of three known major loci on the HbF trait (HBG2, rs748214; BCL11A, rs4671393; and HBS1L-MYB, rs28384513, rs489544 and rs9399137) and HbF levels in SCA patients from the State of Pará, Northern Brazil. Our results showed that high levels of HbF were primarily influenced by alleles of BCL11A (rs4671393) and HMIP (rs4895441) loci, and to a lesser extent by rs748214 Gγ-globin (HBG2) gene promoter. The SNPs rs4671393 and rs4895441 explained 10% and 9.2%, respectively, of the variation in HbF levels, while 4.1% of trait variation was explained by rs748214. The results can be considered as in accordance with the pattern of ancestry displayed by the SCA patients: 39.6% European, 29.6% African and 30.8% Native American, and reinforce the suggestion that studies of as...
2021
Patients with sickle cell disease (SCD) in Kuwait have elevated HbF levels ranging from ~10–44%; however, the modulating factors are unclear. We investigated the association of single nucleotide polymorphisms (SNPs) at BCL11A, HBS1L-MYB and HBB with HbF levels in 237 Kuwaiti SCD patients, divided into 3 subgroups according to their HbF levels. Illumina Ampliseq custom DNA panel was used for genotyping and confirmed by arrayed primer extension or Sanger sequencing. In the BCL11A locus, the CC genotype of rs7606173 [χ2 = 16.5] and (GG) of rs10195871 [χ2 = 15.0] were associated with Hb-F1 and HbF-2 subgroups, unlike rs1427404-T [χ2 = 17.3], which showed the highest association across the three subgroups. HBS1L-MYB locus revealed 2 previously-described SNPs (rs66650371 [χ2 = 9.5] and rs35795442 [χ2 = 9.2]) and 2 previously-unreported SNPs, (rs13220662 [χ2 = 6.2] and rs1406811 [χ2 = 6.7]) that were associated with the HbF-3 subgroup, making this the key locus elevating HbF to the highest...
2018
Sickle cell disease has a great variability of clinical and biological expression that depends on modulatory and environmental genetic factors. This variability in clinical and biological expression encourages us to look for predictors of severity. Hemoglobin F and its genetic determinants are influencing prognostic factors. The objectives of this study were to: determine the prevalence of the Senegal haplotype in homozygous sickle cell patients, study the relationship between this haplotype and the hemoglobin F level and evaluate its influence on the complications of the disease. This is a cross-sectional prospective study that included 100 homozygous sickle cell patients aged over 15 years. A questionnaire was used to collect epidemiological, clinical and biological variables. The hemoglobin F level was measured by capillary method and the analysis of point mutations by restriction fragment length polymorphism (RFLP). These data were collected and analyzed with the software Epi-in...
British journal of haematology, 2016
The presence of high levels of fetal haemoglobin (HbF) provides well-validated clinical benefits to patients with sickle cell anaemia (SCA). Nevertheless it has been difficult to show clear direct effects of the known genetic HbF modifiers, such as the enhancer polymorphisms for haematopoietic transcription factors BCL11A and MYB, on SCA severity. Investigating SCA patients from Brazil, with a high degree of European genetic admixture, we have detected strong effects of these variants on HbF levels. Critically, we have shown, for the first time, that the presence of such HbF-promoting variants leads to a reduced rate of SCA complications, especially stroke.
Evolutionary Bioinformatics, 2015
Sickle cell disease (SCD) is a multisystem disorder characterized by chronic hemolytic anemia, vaso-occlusive crises, and marked variability in disease severity. Patients require transfusions to manage disease complications, with complements, directed by complement regulatory genes (CR1) and its polymorphisms, implicated in the development of alloantibodies. We hypothesize that CR1 polymorphisms affect complement regulation and function, leading to adverse outcome in SCD. To this end, we determined the genomic diversity of complement regulatory genes by examining single nucleotide polymorphisms associated with Knops blood group antigens. Genomic DNA samples from 130 SCD cases and 356 control Africans, 331 SCD cases and 497 control African Americans, and 254 Caucasians were obtained and analyzed, utilizing a PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) assay. Analyzing for ethnic diversity, we found significant differences in the genotypic and allelic frequencies of Sl1/Sl2 (rs17047661) and McCa/b (rs17047660) polymorphisms between Africans, African Americans, and Caucasians (P , 0.05). The homozygote mutant variants had significantly higher frequencies in Africans and African Americans but were insignificant in Caucasians (80.2% and 59.6% vs 5.9% for Sl1/2; and 36% and 24% vs 1.8% for McCa/b). With SCD, we did not detect any difference among cases and controls either in Africa or in the United States. However, we found significant difference in genotypic (P , 0.0001) and allelic frequencies (P , 0.0001) of Sl1/Sl2 (rs17047661) and McCa/b (rs17047660) polymorphisms between SCD groups from Africa and the United States. There was no difference in haplotype frequencies of these polymorphisms among or between groups. The higher frequency of CR1 homozygote mutant variants in Africa but not United States indicates a potential pathogenic role, possibly associated with complicated disease pathophysiology in the former and potentially protective in the latter. The difference between sickle cell groups suggests potential genetic drift or founder effect imposed on the disease in the United States, but not in Africa, and a possible confirmation of the ancestral susceptibility hypothesis. The lower haplotype frequencies among sickle cell and control populations in the United States may be due to the admixture and the dilution of African genetic ancestry in the African American population.
International Journal of Clinical Medicine
Background: Sickle cell disease and sickle cell trait are common erythrocyte disorders that are most often caused by a point mutation (rs334, designated HbS) in the hemoglobin beta gene (HBB); however of this fact, there is extreme variability in occurrence and clinical presentation of sickle cell disease which may be explained by some other genetic changes associated with the gene. In the present study we examined the association between HBB gene polymorphism rs33949930 T>C in the occurrence of sickle cell disease in Saudi Arabia population. Materials and Methods: A case control study of 100 sickle cell disease patients and 100 healthy controls from Tabuk, Saudi Arabia. HBB gene rs33949930 T>C polymorphism was analyzed using Allele specific polymerase chain reaction technique. Results: It was observed that the genotype percentages TT, TC and CC among the patients with sickle cell disease were 63.0%, 35.0% and 2.0% and healthy controls were 68.0%, 27.0% and 5.0% respectively. Allele frequency for T allele was observed to be fT = 0.20 and fT = 0.19, where as for C allele was fC = 0.80 and fC = 0.81 among cases and controls respectively (p = 0.29). Compared to the TT genotype, the odds ratio of 1.4 (95% CI 0.76-2.57), risk ratio of 1.2 (95% CI 0.86-1.65) and risk difference of 8.4 (−6.66-23.38) for heterozygous genotype of HBB rs33949930 T>C was observed in relation to sickle cell disease. In addition, some difference in the laboratory values was observed among sickle cell disease patients with the different variants of HBB gene rs33949930 T>C polymorphism, especially the carriers of heterozygous TC genotype;
International Journal of Contemporary Medicine, 2021
Background: Sickle cell disease (SCD) is an inherited blood disorder that affects red blood cells. The study of various modulating factors, and genetic factors affecting the clinical severity of the SCD is an interesting research focus especially in communities with a distinct genetic background. The XmnI polymorphism is a common genetic variation that was reported in previous studies to increase fetal hemoglobin (HbF) level. This was a descriptive cross-sectional study, conducted in El-Obeid city in Northern Kordofan state, western Sudan, during the period from August to November 2016. The Xmn1 polymorphic site was determined by polymerase chain reaction. Data was analyzed using SPSS software program version 20. P-value of 0.05 and below was considered of significance. In present study HbF level among normal individuals AA , shown significant difference (p<0.05) between presence of Xmnl +/+ and absence of Xmnl-/-site. in patients with SS , the HbF level was higher in those who had one or two Xmnl sites as compared to those with the site absent. In patients with sickle cell trait AS and AA, only the presence of the one and two Xmnl site (+/+) compared to the absence of the site (-/-) was associated with significant increase in the HbF level. There is a close link between the Xmn1 polymorphism site and HbF level. A wide range of HbF level was obtained both in the present and absence of this site. Further studies with a large sample size as well as analysis BS haplotypes among the patient with sickle cell anemia population are needed for better understand of possible association .
2021
Haptoglobin is a protein involved in protecting the body from the harmful effects of free hemoglobin. The haptoglobin gene exhibits a polymorphism, and the different genotypes do not have the same capacity to combat the free hemoglobin effects. The present study aimed at determining the polymorphic distribution of haptoglobin in sickle cell patients (SCPs) from West Cameroon and their impact on the hematological parameters, as well as clinical manifestations of the disease severity. Haptoglobin genotype of 102 SCPs (SS) and 115 healthy individuals (60 AA and 55 AS) was determined by allele-specific polymerase chain reaction, and the complete blood count was determined using the AutoAnalyser. Results showed that the genotype Hp2-2 was significantly ( p < 0.05) represented in SS patients (54%) than in controls AA and AS (27% and 29%, respectively), while Hp2-1 was mostly found ( p < 0.05) in AS (42%) and AA (38%), against 15% in SS. The allelic distribution in SS patients was ...