ABSTRACT
BACKGROUND: Sickle cell disease is the commonest geneticdisorder in Nigeria, affecting 23% of an estimated population of 160million people. The role of genetic mutations in folate cycle genes,and the variable phenotypic expressions constituting disease severity,needs to be critically examined.OBJECTIVE: This study was carried out to establish the pattern ofmethionine synthase gene mutations (rs1805087 SNP), and its possibleassociation with disease severity in adults with sickle cell anaemia inLagos, Nigeria.METHODOLOGY: This is a cross-sectional study of seventy (70)subjects with sickle cell disease (HbSS) matched for age and genderwith known apparently healthy haemoglobin genotype AA (HbAA)subjects, as cases and controls respectively. Structured questionnaireswere used to obtain demographic, clinical and other phenotypic dataneeded to compute disease severity. Pattern of MTR A2756G genemutation and homocysteine assay (Hcy) were assessed by PolymeraseCh ain Reaction and Enzyme- linked Immun osorbent Assayrespectively. Full blood count analysis of participants was done usingthe KX-21 Automated Analyzer (Sysmex Corporation, Japan).RESULTS: The mutant genotypes MTR 2756 AG/GG were recordedin 46.4% (n =55) of subjects with disease severity score >7. Elevatedplasma homocysteine (HHcy) was significantly associated withdisease severity among HbSS subjects (OR=17.2, CI: 3.490-86.079;p=0.0001). Conversely, no significant association was observed withthe mutant genotypes MTR 2756 AG/GG and disease severity(p>0.05).CONCLUSION: While HHcy is significantly associated withphenotypic expression of HbSS, the MTR 2756 SNPs did not appearto independently influence homocysteine level or disease severity inHbSS subjects