Role of low-density lipoprotein receptor rs5925 (1959C>T) gene polymorphism in pathogenesis of dyslipidemia among Egyptian lupus nephritis patients
1Department of Internal Medicine, Faculty of Medicine, Cairo University, Cairo, Egypt
2Department of Nephrology, Ahmed Maher Teaching Hospital, Cairo, Egypt
3Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt
Keywords: Dyslipidemia, gene polymorphism, low-density lipoprotein cholesterol, lupus, nephritis.
Objectives: This study aims to investigate the prevalence of low-density lipoprotein receptor (LDL-R) rs5925 genetic variants and to evaluate their relationship with plasma lipid and kidney functions in lupus nephritis patients.
Patients and methods: Between September 2020 and June 2021, a total of 100 lupus nephritis patients (8 males, 92 females; mean age: 31.1±1.1 years; range, 20 to 67 years) and a total of 100 age- and sex-matched healthy volunteers (10 males, 90 females; mean age: 35.8±2.8 years; range, 21 to 65 years) were included. The gene polymorphism rs5925 (LDLR) was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR‐RFLP). Lipid profile and kidney functions were measured.
Results: Regarding rs5925 (LDLR), C allele was significantly higher among lupus nephritis patients (60%) compared to the control group (45%). While T allele was significantly lower in lupus nephritis patients (40%), compared to the control group (p=0.003). The plasma level of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) were significantly lower in lupus nephritis patients with TT and CT genotypes, compared to those with CC genotype. Moreover, atherogenic index of plasma (AIP) and LDL-C/high-density lipoprotein cholesterol (HDL-C) ratio were significantly lower in patients with TT genotype, compared to the patients with CC genotype. There was a strong and clear association between patients with renal biopsies grades III & IV & V and LDLR C allele (p=0.01, p=0.003, and p=0.004, respectively).
Conclusion: C allele is the significantly prevailed LDLR C1959T variant among lupus nephritis patients. Moreover, LDL-R genetic variant may be one of the non-immunological mechanisms implicated in the disturbed lipid profile among lupus nephritis patients. Profound dyslipidemia may partly underscore the deterioration of kidney function among lupus nephritis patients.