Association Of Genetic Variants Rs1888747 And Rs10868025 Of FRDM3 Gene With Diabetic Neuropathy In Pakistani Patients

Abstract

Background: Diabetic kidney disease (DKD) may cause renal failure, in up to 26% of the patients who are undergoing dialysis for kidney disease. The gene transmission process is not completely understood but it is supposed to be polygenic mechanism and expresses itself in preferable environment suggesting gene-environment interaction. Genome wide-association (GWAS) studies have provided mixed results about gene expression.

Methodology: A case-control study methodology was be implemented in this study. 1050 patients of diabetes mellitus type 2 (DMT2) were selected from Pakistan Institute of Medical Sciences PIMS, department of medicine. The cases were divided into two groups of early and advanced DKD (albuminuria 30-299mg/24h and ≥300mg/24h respectively). There were 370 controls, 352 cases with early DKD and 328 cases with advanced DKD. DNA was isolated from peripheral blood and FRMD3 expression in kidney tissue samples was studies through kidney biopsy samples.

Results: Among all types of SNPs one was significantly associated with the particular disease and that was rs1888747, rs10868025 did not show any association on statistical analysis. The associations were observed in recessive models. To perform regression, the model wars adjusted for diabetes typeII duration, gender of the patient, BP readings and lipid file, the association still persisted. None of the other NSPs were found associated with this disease

Conclusion: The FRMD3 protein expression negatively correlates with FRMD3 genes, so it is good candidate gene for the development of albuminuria. Further exploration is suggested to determine the exact mechanisms for correlation.