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. 2022 Apr 12;17(4):e0266603.
doi: 10.1371/journal.pone.0266603. eCollection 2022.

Low levels of soluble DPP4 among Saudis may have constituted a risk factor for MERS endemicity

Khaled R Alkharsah  1 , Salma Ali Aljaroodi  1 , Jawad Ur Rahman  1 , Awatif N Alnafie  2 , Reem Al Dossary  1 , Reem Y Aljindan  1 , Amani M Alnimr  1 , Jamal Hussen  3
Affiliations

Low levels of soluble DPP4 among Saudis may have constituted a risk factor for MERS endemicity

Khaled R Alkharsah et al. PLoS One. .

Abstract

Most of the cases of Middle East respiratory syndrome coronavirus (MERS-CoV) were reported in Saudi Arabia. Dipeptidyl peptidase-4 (DPP4) was identified as the receptor for the virus. The level of soluble DPP4 (sDPP4) was found to be reduced in MERS-CoV infected patients while high levels of sDPP4 were suggested to be protective against MERS-CoV in animal models. We investigated whether the Saudi population has lower levels of sDPP4 which makes them more susceptible to MERS-CoV infection and, therefore, could explain the larger number of cases from the country. Blood samples were collected from 219 Saudi blood donors and 200 blood donors from other ethnic groups. The plasma level of sDPP4 was measured by ELISA and the following SNPs in the DPP4 gene; rs35128070, rs1861978, rs79700168, and rs17574, were genotyped by TaqMan SNP genotyping assay. The average level of plasma sDDP4 was significantly lower in Saudis than other Arabs and non-Arabs (P value 0.0003 and 0.012, respectively). The genotypes AG of rs35128070 and GT of rs1861978 were significantly associated with lower sDPP4 among Saudis (P value 0.002 for each). While both genotypes AA and AG of rs79700168 and rs17574 were associated with significantly lower average sDPP4 level in Saudis compared to other ethnic groups (P value 0.031 and 0.032, and 0.027 and 0.014, respectively). Herein, we report that the Saudi population has lower levels of plasma sDPP4 than other ethnic groups, which is associated with genetic variants in the DPP4 gene. This may have contributed to increase the susceptibility of the Saudi population to MERS-CoV infection and could be a factor in the long-lasting persistence of the virus in the country.

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Conflict of interest statement

The authors have declared that no competing interests exist

Figures

Fig 1
Fig 1. Standard curve for sDPP4 concentration.
To determine the concentration of sDPP4 in the plasm samples, Graphpad Prism was used to fit a standard curve using nonlinear regression (curve fitting). The samples were diluted 100-fold before running the assay and the result was then multiplied by the dilution factor.
Fig 2
Fig 2
Average sDPP4 level among the study population according to (A) ethnicity, (B) Gender, and (C) age group.
Fig 3
Fig 3. Average sDPP4 levels among different ethnic groups in relation to the rs35128070 genotypes.
Fig 4
Fig 4. Average sDPP4 levels among different ethnic groups in relation to the rs1861978 genotypes.
Fig 5
Fig 5. Average sDPP4 levels among different ethnic groups in relation to the rs79700168 genotypes.
Fig 6
Fig 6. Average sDPP4 levels among different ethnic groups in relation to the rs17574 genotypes.
See this image and copyright information in PMC

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Grants and funding

This project was funded by the Deanship of Scientific Research at Imam Abdulrahman Bin Faisal University (Project number: 2019-396-Med) https://www.iau.edu.sa/en/administration/deanships/deanship-of-scientific-research The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.