A cross-sectional clinic-based study exploring whether variants within the glutathione S-transferase, haptoglobin and uridine 5'-diphospho-glucuronosyltransferase 1A1 genes are associated with interindividual phenotypic variation in sickle cell anaemia in Jamaica.

Objectives: To explore putative associations between specific variants in either the glutathione S-transferase (GST), haptoglobin (HP) or uridine 5'-diphospho-glucuronosyl-transferase 1A1 (UGT1A1) genes and clinically important phenotypes in sickle cell anaemia (HbSS). Methods: 371 HbSS participants were recruited from the Sickle Cell Clinic of the Sickle Cell Unit at the University of the West Indies, Kingston, Jamaica. Markers within four GST superfamily genes, the HP gene and the UGT1A1 gene were analysed using PCR-based assays. Results: Multivariable regression revealed statistically significant associations between the GSTP1 Ile105Val heterozygote and HbA(2) levels (P = .016), HbF percentage (P = .001), MCH concentration (P = .028) and reticulocyte count (P = .032), while the GSTM3 D/D homozygote was significantly associated with HbA(2) levels (P = .032). The UGT1A1 (TA)(6)/(TA)(8) heterozygote showed statistically significant associations with HbA(2) levels (P = .019), HbF percentage (P < .001), haemoglobin levels (P = .008), PCV values (P = .007) and RBC counts (P = .041). Conclusion: This exploratory cross-sectional study has generated novel and informative genotype-phenotype estimates of association, but larger studies are needed to determine whether these specific variants within the GST, UGT1A1 and HP genes are related to interindividual phenotypic variability in HbSS.