Manifestation of rs1888747 polymorphisms in the FRMD3 gene in diabetic kidney disease and diabetic retinopathy in type 2 diabetes patients

Kidney Res Clin Pract. 2021 Jun;40(2):263-271. doi: 10.23876/j.krcp.20.190. Epub 2021 Jun 2.

Abstract

Background: FRMD3 polymorphisms has suggested that they could be an alternative test to differentiate diabetic nephropathy (DN) from nondiabetic renal disease (NDRD) in type 2 diabetes mellitus (DM) patients. This study was performed to investigate the relationship between the FRMD3 gene and clinical characteristics of DN.

Methods: Patients who already had renal pathologic results were tested for FRMD3 polymorphisms. The subjects were classified into three groups; DN with diabetic retinopathy (DR), DN without DR, and DM with NDRD. FRMD3 polymorphisms were analyzed in each group.

Results: The prevalence of GG, CG, and CC was 44.4%, 42.2%, and 13.3% respectively. There was no significant difference in clinical parameters, which consisted of disease duration, proteinuria, and complications in DN with or without DR and DM with NDRD. The G allele was mainly found in DN with DR patients (50.8%) whereas the C allele was found in DM with NDRD patients (43.5%) (p = 0.02). There was a significant association between the CC genotype in NDRD when compared to GG (p = 0.001). In addition, the C allele was 2.10-fold more often associated with NDRD than the G allele (p = 0.03). The CC genotype was correlated with risk for NDRD than the GG and GC genotypes, with odds ratios of 6.89 and 4.91, respectively (p = 0.02).

Conclusion: C allele presentation, especially homozygous CC, was associated with NDRD pathology in patients with overt proteinuria. Hence, kidney biopsy is suggested in those with the C allele or homozygous CC genotype, regardless of retinopathy manifestations.

Keywords: Diabetic kidney disease; Diabetic nephropathies; Diabetic retinopathy; FRMD3 gene.