A study on the genotype frequency of $$-158~\hbox {G}\gamma $$ - 158 G γ ( $$\hbox {C}{\rightarrow }\hbox {T}$$ C → T ) Xmn1 polymorphism in a sickle cell trait cohort from Siwa Oasis, Egypt

Abstract

Sickle cell haemoglobinopathy is a genetic disorder caused by the presence of haemoglobin S (HbS) including sickle cell disease (SCD) (sickle cell anemia, HbS/β -thalassaemia and HbSC disease) and sickle cell trait. In Siwa Oasis, most remote oasis town in Egypt, the prevalence rate of sickle cell haemoglobinopathy is approaching 20%. The 1 polymorphism was reported to increase the HbF level ameliorating the severity of the SCD. The present study aims mainly to investigate the genotype frequency of -158Gγ (C→T) Xmn1 polymorphism in Siwa Oasis, Egypt and to study, if possible, any association with increased HbF expression. This study was performed on 62 sickle cell carriers (AS), three cases of sickle cell anaemia (SS) detected during a screening programme conducted on primary school children in Siwa Oasis by Alexandria Faculty of Medicine in 2011-2012. Sixty-five age-matched and sex-matched healthy controls (AA) were included. All enrolled children were subjected to PCR-RFLP for the detection of -158Gγ (C→T) Xmn1 polymorphism using the Xmn1 restriction enzyme. Genotyping of the -158Gγ (CvT) Xmn1 polymorphism revealed that among AS, 85.5% were homozygous for the wild-type allele (CC) and 14.5% were heterozygous (CT). However, among SS, two cases were homozygous for the wild-type allele (CC) and one case was heterozygous (CT). The genotype frequencies among AA were 83.1% homozygous for the wild-type allele (CC) and 16.9% heterozygous (CT). None of the studied cases or controls was homozygous for the mutant allele (TT). Among both AS and AA, there was no significant difference between the wild-type and heterozygous genotypes regarding HbF level. Studying genotype frequency of the1 γG globin polymorphism (-158C>T ) in Siwa Oasis, Egypt can be considered as a starting point for further research targeting this community sector. However, in our studied cohort, there were only three sickle cell anaemia patients. Further, none of the tested cases or controls was found to be homozygous for the mutant allele (TT). In the absence of any homozygous genotype for the mutant allele (TT) in the studied cohort, any reasonable conclusion on the effect of polymorphism on increase in HbF could not be established. Further studies with a larger sample size are needed for better understanding of the possible association.

Association Between Selected Single Nucleotide Polymorphisms in Globin and Related Genes and Response to Hydroxyurea Therapy in Ghanaian Children with Sickle Cell Disease

“…The most frequent genotype with the Xmn1 polymorphism observed was homozygosity (CC) for the absence of the Xmnl site in both HU+ and HU- populations. The homozygous mutant (TT), similar to the findings from a recent study 29 was also not observed in our study, thus limiting our ability to draw any conclusions on the influence of this genotype on HbF.…”

“…The association between HbF levels and polymorphisms presented by SNPs in BCL11A gene and the Xmn1 gene has been demonstrated in different populations. 11 , 16 , 25–27 , 29–35 While HbF regulation is highly diversified and genetically controlled, reproducing association studies across different populations, particularly of diverse genetic backgrounds and environmental setting is likely to produce different observations in different studies. Interestingly, we observed a slightly reduced Hb level in the HU+ group and speculate that, this could be due to crenation and subsequent lysing of RBC’s since HU plays a role in RBC differentiation.…”

Molecular Analysis of Xmn1-Polymorphic Site ´5 to Gγ of the β-Globin Gene Cluster in a Saudi Population of Jazan Region in Correlation with Hb F Expression

“…Sickle cell anemia (SCA) is a particularly common genetic disorder in some parts of Saudi Arabia [ 2 , 8 ]. The polymorphism in the β chain of Hb S and patient prognosis can be predicted by combining the levels of Hb F with a determination of which Xmn1 ′5 to G γ is present [ 9 ]. High levels of the former can interact with the latter to reduce disease severity [ 10 ].…”

“…They are designated as Senegal, Benin, Bantu, Cameroon, and Arab-Indian haplotypes. The latter was discovered with the presence of Xmn1 ′5 to G γ in the Arabian Gulf region and India with fewer clinical symptoms as the Hb F is present in high levels in comparison with the haplotypes in Africa [ 8 , 9 ]. The Senegal and Arab-Indian haplotypes are positive in Xmn1 ′5 to G γ , having the same mutation (C--T) and also a high level of Hb F as well [ 8 , 10 ].…”

“…SCA is a type of Hb variant, most commonly detected in most African and Asian countries, including Saudi Arabia, where it is a special problem in many areas [ 3 , 5 ]. There is a polymorphism in the β -globin gene of Hb S, and patient prognosis can be predicted by combining the Hb F levels with a determination of which β s haplotypes are present [ 9 , 10 ]. High levels of the former can act with the latter to alleviate disease severity and in turn lower mortality rate [ 10 , 13 , 14 ].…”