Distribution of PON1 (Q192R) and ENPP1 (K173Q) gene polymorphisms in patients with sickle cell disease, sickle cell trait and healthy individuals

Hemoglobinopathies, such as sickle cell disease (SCD) cause major morbidity; however, non‑globin gene variants remain largely underexplored. The present study analyzed 23 patients with SCD, 57 patients with sickle cell heterozygotes, and 66 healthy subjects as the controls. Hemoglobin variants were identified by high performance liquid chromatography. Genotyping for paraoxonase 1 (PON1; Q192R) and ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1; K173Q) polymorphisms was performed by conventional allele‑specific PCR. Genetic association analyses were restricted to comparisons between patients with SCD and the healthy controls only. Allele‑based analysis revealed that the R allele of PON1 was significantly less frequent in patients with SCD compared with the controls [odds ratio (OR), 0.36; 95% confidence interval (CI), 0.17=0.73; P<0.001]. For ENPP1, the Q allele was enriched in patients with SCD compared with the controls, corresponding to a 2.89‑fold higher odds of disease in Q‑allele carriers relative to K‑allele carriers (OR, 2.89; 95% CI, 1.41‑5.93; P=0.008). Linear regression analysis under an additive model revealed no significant association between the PON1 Q192R or ENPP1 K173Q genotypes and fetal hemoglobin levels. These findings demonstrate population‑level differences in the distribution of PON1 and ENPP1 polymorphisms and underscore the need for larger studies to clarify their potential relevance in SCD.