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

  • Authors:
    • Charmi Jyotishi
    • Drishti Valechha
    • Mansi Patel
    • Suresh Prajapati
    • Ashish Jawarkar
    • Reeshu Gupta
  • View Affiliations / Copyright

    Affiliations: Parul Institute of Applied Sciences, Parul University, Post Limda, Vadodara, Gujarat 391760, India, Research and Development Cell, Parul University, Post Limda, Vadodara, Gujarat 391760, India, Department of Pathology, Parul University, Post Limda, Vadodara, Gujarat 391760, India
    Copyright: © Jyotishi et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].
  • Article Number: 50
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    Published online on: April 24, 2026
       https://doi.org/10.3892/wasj.2026.465
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Abstract

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. 
View Figures

Figure 1

Representative agarose gel
electrophoresis image illustrating allele-specific PCR
amplification for the PON1 Q192R polymorphism. Lane M, 100 bp DNA
ladder; lanes P1, heterozygous AG genotype (bands at ~236 bp and
~302 bp); lanes P2, homozygous AA genotype (single band at ~302
bp); lanes P3, homozygous GG genotype (single band at ~236 bp). PCR
products were resolved on a 3% agarose gel and visualized under UV
illumination. The expected band sizes correspond to the presence of
Q (A allele, 302 bp) and R (G allele, 236 bp) variants.

Figure 2

Sanger sequencing chromatogram
illustrating the Q192R (rs662) polymorphism in the PON1 gene. The
zoomed electropherogram highlights codon 192. The presence of
overlapping G and A peaks at the second position (C(G/A)A)
indicates a heterozygous genotype (QR), corresponding to both
glutamine (CAA) and arginine (CGA) alleles.

Figure 3

Representative 3% agarose gel
electrophoresis image illustrating allele-specific PCR
amplification for the ENPP1 K121Q polymorphism. Lane M, 100 bp DNA
ladder; lanes P1 and P3, homozygous KK genotype, indicating a
single band at 99 bp; lanes P2, homozygous QQ genotype, indicating
a single band at 107 bp; lanes P4, heterozygous KQ genotype, with
two distinct bands at 99 bp and 107 bp. PCR products were resolved
on a 3% agarose gel, stained with ethidium bromide, and visualized
under UV light. Band sizes correspond to the presence of
allele-specific amplification products for the K and Q
variants.
View References

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Copy and paste a formatted citation
Spandidos Publications style
Jyotishi C, Valechha D, Patel M, Prajapati S, Jawarkar A and Gupta R: Distribution of PON1 (Q192R) and ENPP1 (K173Q) gene polymorphisms in patients with sickle cell disease, sickle cell trait and healthy individuals. World Acad Sci J 8: 50, 2026.
APA
Jyotishi, C., Valechha, D., Patel, M., Prajapati, S., Jawarkar, A., & Gupta, R. (2026). Distribution of PON1 (Q192R) and ENPP1 (K173Q) gene polymorphisms in patients with sickle cell disease, sickle cell trait and healthy individuals. World Academy of Sciences Journal, 8, 50. https://doi.org/10.3892/wasj.2026.465
MLA
Jyotishi, C., Valechha, D., Patel, M., Prajapati, S., Jawarkar, A., Gupta, R."Distribution of PON1 (Q192R) and ENPP1 (K173Q) gene polymorphisms in patients with sickle cell disease, sickle cell trait and healthy individuals". World Academy of Sciences Journal 8.3 (2026): 50.
Chicago
Jyotishi, C., Valechha, D., Patel, M., Prajapati, S., Jawarkar, A., Gupta, R."Distribution of PON1 (Q192R) and ENPP1 (K173Q) gene polymorphisms in patients with sickle cell disease, sickle cell trait and healthy individuals". World Academy of Sciences Journal 8, no. 3 (2026): 50. https://doi.org/10.3892/wasj.2026.465
Copy and paste a formatted citation
x
Spandidos Publications style
Jyotishi C, Valechha D, Patel M, Prajapati S, Jawarkar A and Gupta R: Distribution of PON1 (Q192R) and ENPP1 (K173Q) gene polymorphisms in patients with sickle cell disease, sickle cell trait and healthy individuals. World Acad Sci J 8: 50, 2026.
APA
Jyotishi, C., Valechha, D., Patel, M., Prajapati, S., Jawarkar, A., & Gupta, R. (2026). Distribution of PON1 (Q192R) and ENPP1 (K173Q) gene polymorphisms in patients with sickle cell disease, sickle cell trait and healthy individuals. World Academy of Sciences Journal, 8, 50. https://doi.org/10.3892/wasj.2026.465
MLA
Jyotishi, C., Valechha, D., Patel, M., Prajapati, S., Jawarkar, A., Gupta, R."Distribution of PON1 (Q192R) and ENPP1 (K173Q) gene polymorphisms in patients with sickle cell disease, sickle cell trait and healthy individuals". World Academy of Sciences Journal 8.3 (2026): 50.
Chicago
Jyotishi, C., Valechha, D., Patel, M., Prajapati, S., Jawarkar, A., Gupta, R."Distribution of PON1 (Q192R) and ENPP1 (K173Q) gene polymorphisms in patients with sickle cell disease, sickle cell trait and healthy individuals". World Academy of Sciences Journal 8, no. 3 (2026): 50. https://doi.org/10.3892/wasj.2026.465
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