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. 2023 May 3;13(1):7215.
doi: 10.1038/s41598-023-34396-1.

Role of paraoxonase 1 activity and PON1 gene polymorphisms in sickle cell disease

Joelma Figueiredo Menezes  1   2   3 , Magda Oliveira Seixas Carvalho  1   4 , Larissa Carneiro Rocha  3 , Felipe Miranda Dos Santos  5 , Elisângela Vitória Adorno  2 , Cyntia Cajado de Souza  1 , Rayra Pereira Santiago  1 , Caroline Conceição da Guarda  1 , Rodrigo Mota de Oliveira  1 , Camylla Vilas Boas Figueiredo  1 , Suéllen Pinheiro Carvalho  1 , Sètondji Cocou Modeste Alexandre Yahouédéhou  1 , Luciana Magalhães Fiuza  1 , Corynne Stéphanie Ahouefa Adanho  1 , Thassila Nogueira Pitanga  1 , Isa Menezes Lyra  3   6 , Valma Maria Lopes Nascimento  3 , Alberto Augusto Noronha-Dutra  4 , Marilda Souza Goncalves  7   8
Affiliations

Role of paraoxonase 1 activity and PON1 gene polymorphisms in sickle cell disease

Joelma Figueiredo Menezes et al. Sci Rep. .

Abstract

Sickle cell disease (SCD) patients often exhibit a dyslipidemic sub-phenotype. Paraoxonase 1 (PON 1) is a serum glycoprotein associated with the high-density lipoproteins cholesterol (HDL-C), and variability in PON1 activity depends on the PON1 genotypes. We investigated the influence of PON1c.192Q > R and PON1c.55L > M polymorphisms on PON1 activity and laboratory parameters and the association between PON1 activity and clinical manifestations in SCD patients. We recruited 350 individuals, including 154 SCD patients and 196 healthy volunteers, which comprised the control group. Laboratory parameters and molecular analyses were investigated from the participants' blood samples. We have found increased PON1 activity in SCD individuals compared to the control group. In addition, carriers of the variant genotype of each polymorphism presented lower PON1 activity. SCD individuals carrying the variant genotype of PON1c.55L > M polymorphism had lower platelet and reticulocyte counts, C-reactive protein, and aspartate aminotransferase levels; in addition to higher creatinine levels. SCD individuals carrying the variant genotype of PON1c.192Q > R polymorphism had lower triglyceride, VLDL-c, and indirect bilirubin levels. Furthermore, we observed an association between PON1 activity history of stroke and splenectomy. The present study confirmed the association between PON1c.192Q > R and PON1c.55L > M polymorphisms and PON1 activity, in addition to demonstrate their effects on markers of dislipidemia, hemolysis and inflammation, in SCD individuals. Moreover, data suggest PON1 activity as a potential biomarker related to stroke and splenectomy.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Evaluation of PON1 activity in SCD patients and control group. SCD individuals exhibited increased levels of PON1 activity (Control group n = 85 and SCD n = 124). P-value obtained with Mann–Whitney Test.
Figure 2
Figure 2
Carriers of the variant genotype of PON1c.55L > M and PON1c.192Q > R have decreased PON1 activity. (A) SCD individuals carrying the variant genotype of PON1c.55L > M presented decreased PON1 activity (wild-type = 93 and variant = 16). (B) SCD individuals carrying the variant genotype of PON1c.192Q > R exhibited decreased PON1 activity (wild-type = 40 and variant = 70). (C) Individuals in the control group carrying the variant genotype of PON1c.55L > M presented decreased PON1 activity (wild-type = 71 and variant = 16). (D) No statistical significance was found among carriers of the variant genotype of PON1c.192Q > R in the control group (wild-type = 14 and variant = 71). PON1c.55L > M: LL (wild type) and LM + MM (variant) genotypes. PON1c.192Q > R: QQ (wild-type) and (QR + RR) variant genotypes. Mann–Whitney U test was used to calculate the P-value.
Figure 3
Figure 3
Association of laboratory parameters with different genotypes of PON1 among SCD individuals. SCD individuals with the variant genotype for PON1c.55L > M exhibited (A) decreased platelet count (wild-type = 108 and variant = 22); (B) increased creatinine levels (wild-type = 107 and variant = 22); (C) decreased CRP levels (wild-type = 108 and variant = 22); (D) decreased reticulocyte counts (wild-type = 96 and variant = 22); (E) decreased AST levels (wild-type = 108 and variant = 22). SCD individuals with the variant genotype of PON1c.192Q > R had (F) decreased triglyceride levels (wild-type = 17 and variant = 116); (G) decreased VLDL-c levels (wild-type = 17 and variant = 116); (H) decreased indirect bilirubin (wild-type = 17 and variant = 116). PON1c.55L > M: LL (wild type) and LM + MM (variant) genotypes. PON1c.192Q > R: QQ (wild-type) and (QR + RR) variant genotypes. Mann–Whitney U test was used to calculate the P-value.
Figure 4
Figure 4
Analysis of the clinical history of individuals with SCD and PON1 activity. SCD individuals with previous stroke had decreased PON1 activity; SCD individuals with previous splenectomy exhibited increased PON1 activity. Five patients had previous stroke history, and 6 patients had undergone splenectomy. P-value was obtained with Mann–Whitney.
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