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

Abstract

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® . A total of 436 hydoxycarbamide- and opioid-naïve patients were studied; median age was 16years. 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.