12 - Investigation and Management of Megaloblastic Anaemia

Abstract

Four SNPs (rs7482144, rs4671393, rs28384513 and rs4895441) associated with HbF levels have been identified in different populations worldwide. To explore whether these SNPs modulate HbF expression in Chinese Zhuang population, 436 Chinese Zhuang β-thalassemia intermedia (β-TI) patients were divided into high HbF level group (mean HbF = 25.5%, n = 218) and low group (mean HbF = 6.51%, n = 218) for genotyping using PCR-HRM method. Results demonstrated that there was a significantly higher minor allele frequency (MAF = 34.2%) of rs4895441 (G) in HMIP in high HbF level group than that in low group (MAF = 19.8%) (P = 0.001, OR = 1.73, 95% CI: 1.24–2.57). The cumulative effects of risk genotypes of these loci for patients carrying any combination of 1, 2 or 3 risk genotype had a gradually increased risk of high HbF level phenotype compared to those without the risk genotypes (OR = 1.50–9.06, P = 0.0008); Gene-gene interaction of rs7842144 and rs4895441 showed the best model with the smallest prediction error (0.4259) and the greatest consistency of coefficient of variation (P = 0.01). We concluded that rs4895441, G on HMIP might be a high-risk modifier variant for high HbF level expression, and HBG2, BCL11A and HMIP genes, as HbF quantitative trait loci (QTL) could have a synergistic effect on increasing the HbF level in Chinese Zhuang β-TI patients.