Clinical and genetic factors are associated with pain and hospitalisation rates in sickle cell anaemia in Cameroon

We aimed to investigate the clinical and genetic predictors of painful vaso-occlusive crises (VOC) in sickle cell disease (SCD) in Cameroon. Socio-demographics, clinical variables/events and haematological indices were acquired. Genotyping was performed for 40 variants in 17 pain-related genes, three fetal haemoglobin (HbF)-promoting loci, two kidney dysfunctions-related genes, and HBA1/HBA2 genes. Statistical models using regression frameworks were performed in R-(R). A total of 436 hydoxycarbamide- and opioid-naive patients were studied; median age was 16 years. Female sex, body mass index, Hb/HbF, blood transfusions, leucocytosis and consultation or hospitalisation rates significantly correlated with VOC. Three pain-related genes variants correlated with VOC (CACNA2D3-rs6777055, P=0.025; DRD2-rs4274224, P = 0.037; KCNS1-rs734784, P = 0.01). Five pain-related genes variants correlated with hospitalisation/consultation rates. (COMT-rs6269, P = 0.027; FAAH-rs4141964, P = 0.003; OPRM1-rs1799971, P = 0.031; ADRB2-rs1042713; P < 0.001; UGT2B7-rs7438135, P = 0.037). The 3.7kb HBA1/HBA2 deletion correlated with increased VOC (P - 0.002). HbF-promoting loci variants correlated with decreased hospitalisation (BCL11A-rs4671393, P = 0.026; HBS1L-MYB-rs28384513, P = 0.01). APOL1 G1/G2 correlated with increased hospitalisation (P = 0.048). This first study from Africa has provided evidence supporting possible development of genetic risk model for pain in SCD.