Potential impact of serpin peptidase inhibitor clade (A) member 4 SERPINA4 (rs2093266) and SERPINA5 (rs1955656) genetic variants on COVID-19 induced acute kidney injury

Sally M El-Hefnawy; Zeinab A Kasemy; Hanaa A Eid; Ibrahim Elmadbouh; Rasha G Mostafa; Thoria A Omar; Heba E Kasem; Eman M Ghonaim; Mohamed M Ghonaim; Amany A Saleh

doi:10.1016/j.mgene.2022.101023

Potential impact of serpin peptidase inhibitor clade (A) member 4 SERPINA4 (rs2093266) and SERPINA5 (rs1955656) genetic variants on COVID-19 induced acute kidney injury

Hum Gene (Amst). 2022 May:32:101023. doi: 10.1016/j.mgene.2022.101023. Epub 2022 May 9.

Authors

Affiliations

¹ Medical Biochemistry & Molecular Biology Department, Menoufia Faculty of Medicine, Egypt.
² Public Health and Community Medicine, Menoufia Faculty of Medicine, Egypt.
³ Chest Diseases and Tuberculosis Department, Menoufia Faculty of Medicine, Egypt.
⁴ Medical Microbiology and Immunology Department, Menoufia Faculty of Medicine, Egypt.
⁵ Clinical Pathology Department, Menoufia Faculty of Medicine, Egypt.
⁶ Internal Medicine Departments, Faculty of Medicine, Menoufia University, Egypt.
⁷ Clinical Pharmacy Department, Faculty of Pharmacy, Tanta University, Egypt.
⁸ Medical Student, Faculty of Medicine, Menoufia University, Egypt.
⁹ Medical Surgical Nursing Department, College of Nursing, Taibah University, Madina, Saudi Arabia.

Abstract

Background: SARS-CoV-2 has a number of targets, including the kidneys. Acute Kidney Injury (AKI) might develop in up to a quarter of SARS-CoV-2 patients. In the clinical environment, AKI is linked to a high rate of death and leads to the progression of AKI to chronic renal disease.

Aim: We aimed to investigate rs2093266 and rs1955656 polymorphisms in SERPINA4 and SERPINA5 genes, respectively, as risk factors for COVID-19 induced AKI.

Subjects and methods: A case-control study included 227 participants who were divided into three groups: 81 healthy volunteers who served as controls, 76 COVID-19 patients without AKI and 70 COVID -19 patients with AKI. The TaqMan assay was used for genotyping the SERPINA4 (rs2093266) and SERPINA5 (rs1955656) polymorphisms by real-time PCR technique.

Results: Lymphocytes and eGFR showed a significantly decreasing trend across the three studied groups, while CRP, d-Dimer, ferritin, creatinine, KIM-1and NGAL showed a significantly increasing trend across the three studied groups (P < 0.001). Rs2093266 (AG and AA) genotypes were significant risk factors among non-AKI and AKI groups in comparison to controls. Rs1955656 (AG and AA) were significant risk factors among the AKI group, while AA was the only significant risk factor among the non-AKI group. Recessive, dominant, co-dominant, and over-dominant models for genotype combinations were demonstrated. The GG v AA, GG + AG v AA, and GG v AG + AA models of the rs2093266 were all significant predictors of AKI, whilst only the GG v AA model of the rs1955656 SNP was a significant predictor. The logistic regression model was statistically significant, χ2 = 56.48, p < 0.001. AKI was associated with progressed age (OR = 0.95, 95% CI: 0.91-0.98, p = 0.006), suffering from chronic diseases (OR = 3.25, 95% CI: 1.31-8.01, p = 0.010), increased BMI (OR = 0.89, 95% CI: 0.81-0.98, p = 0.018), immunosuppressive (OR = 4.61, 95% CI: 1.24-17.16, p = 0.022) and rs2093266 (AG + AA) (OR = 3.0, 95% CI: 1.11-8.10, p = 0.030).

Conclusion: Single nucleotide polymorphisms (rs2093266) at SERPINA4 gene and (rs1955656) at SERPINA5 gene were strongly linked to the development of AKI in COVID-19 patients.

Keywords: AKI; COVID-19; Genotype; Polymorphism; Risk; SNP.