Assessment of MTR Rs1805087 SNP as Possible Modifier of Sickle Cell Disease Severity in a Nigerian Population.

BACKGROUND: Sickle cell disease is the commonest genetic disorder in Nigeria, affecting 2-3% of an estimated population of 160 million 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 of methionine synthase gene mutations (rs1805087 SNP), and its possible association with disease severity in adults with sickle cell anaemia in Lagos, Nigeria. METHODOLOGY: This is a cross-sectional study of seventy (70) subjects with sickle cell disease (HbSS) matched for age and gender with known apparently healthy haemoglobin genotype AA (HbAA) subjects, as cases and controls respectively. Structured questionnaires were used to obtain demographic, clinical and other phenotypic data needed to compute disease severity. Pattern of MTR A2756G gene mutation and homocysteine assay (Hcy) were assessed by Polymerase Chain Reaction and Enzyme- linked Immunosorbent Assay respectively. Full blood count analysis of participants was done using the KX-21 Automated Analyzer (Sysmex Corporation, Japan). RESULTS: The mutant genotypes MTR 2756 AG/GG were recorded in 46.4% (n =55) of subjects with disease severity score >7. Elevated plasma homocysteine (HHcy) was significantly associated with disease severity among HbSS subjects (OR=17.2, CI: 3.490-86.079; p=0.0001). Conversely, no significant association was observed with the mutant genotypes MTR 2756 AG/GG and disease severity (p>0.05). CONCLUSION: While HHcy is significantly associated with phenotypic expression of HbSS, the MTR 2756 SNPs did not appear to independently influence homocysteine level or disease severity in HbSS subjects.

CONTEXTE: La drépanocytose est la maladie génétique la plus répandue au Nigeria, affectant 2 à 3 % d'une population estimée à 160 millions de personnes. Le rôle des mutations génétiques dans les gènes du cycle du folate, et les expressions phénotypiques variables constituant la gravité de la maladie, doivent être examinés de façon critique. OBJECTIF: Cette étude a été menée pour établir le schéma des mutations du gène de la méthionine synthase (rs1805087 SNP), et son association possible avec la gravité de la maladie chez les adultes atteints de drépanocytose à Lagos, au Nigeria. MÉTHODOLOGIE: Il s'agit d'une étude transversale de soixantedix (70) sujets atteints de drépanocytose (HbSS) appariés pour l'âge et le sexe avec des sujets connus apparemment sains de génotype d'hémoglobine AA (HbAA), comme cas et contrôles respectivement. Des questionnaires structurés ont été utilisés pour obtenir des données démographiques, cliniques et autres données phénotypiques nécessaires au calcul de la gravité de la maladie. Le profil de la mutation du gène MTR A2756G et le dosage de l'homocystéine (Hcy) ont été évalués respectivement par réaction en chaîne par polymérase et par test immunologique enzymatique. L'analyse de la formule sanguine complète des participants a été effectuée à l'aide de l'analyseur automatisé KX-21 (Sysmex Corporation, Japon). RÉSULTATS: Les génotypes mutants MTR 2756 AG/GG ont été enregistrés chez 46,4 % (n =55) des sujets présentant un score de gravité de la maladie > 7. L'homocystéine plasmatique élevée (HHcy) était significativement associée à la gravité de la maladie chez les sujets HbSS (OR=17,2, CI : 3,490­86,079 ; p=0,0001). À l'inverse, aucune association significative n'a été observée entre les génotypes mutants MTR 2756 AG/GG et la gravité de la maladie (p>0,05). CONCLUSION: Alors que l'HHcy est significativement associée à l'expression phénotypique de l'HbSS, les SNP MTR 2756 ne semblent pas influencer indépendamment le niveau d'homocystéine ou la gravité de la maladie chez les sujets HbSS.

Assessment of MTR Rs1805087 SNP as Possible Modifier ofSickle Cell Disease Severity in a Nigerian Population

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