SAT091 Genetic Investigation Of The Susceptibility To Develop Type 1 Diabetes And Diabetic Nephropathy

Abstract

Abstract Disclosure: I. Brema: None. A. Aljuryyan: None. B. Bradley: None. A.E. Osman: None. Diabetic Nephropathy (DN) is one of the leading causes of end-stage renal disease (ESRD) worldwide and is a major cause of morbidity and mortality in subjects with type 1 diabetes (T1DM). Several single nucleotide polymorphisms (SNP) have been found in various gene variants such as the ACE, NOS 3, and FRMD 3 genes that play a major role in genetic susceptibility to DN, however, there is lack of wide replication of these studies, particularly in non-Caucasian ethnic groups. Therefore, the aim of this study was to identify SNPs that increase the susceptibility to develop T1DM as well as microalbuminuria (the hallmark of DN) in a Saudi cohort of subjects with T1DM. We conducted a case-control study in 179 subjects with T1DM and 180 healthy normal controls comparing genotype frequency of 11 SNPs that have been shown to increase the susceptibility to develop DN in subjects with T1DM, namely, rs1799983, rs2070744 (NOS3 gene); rs560807, rs 1059982 (CAT gene), rs1888747, rs10868025, rs361525, rs1800629 (FRMD3 gene), rs182052, rs 17300539 (ADIPOQ gene) and rs1799752(ACE gene). We report that the A/G rs361525 (FRMD3) genotype has significantly higher frequency in controls compared to subjects with T1DM (9 % vs 0), p value 0.01) and it seems to be protective against the risk of T1DM development. Moreover, the A/A rs17300539 (ADIPOQ gene) genotype has significant higher frequency in controls compared to subjects with T1DM (7 % vs 0.5), p value 0.02) and seems to be protective against type 1 development as well. We did not detect any further associations between the remaining 9 genotype SNPs and the risk of T1DM. On the other hand, we report no association between all the 11 studied SNPs referenced above and the risk of developing diabetic nephropathy. We have studied several DN susceptibility SNPs that have been shown to increase the risk of albuminuria and ESRD development in Caucasians with T1DM , however, we were unable to replicate previous findings in this Saudi cohort of patients with T1DM. Future larger multicenter studies are needed in larger numbers of patients to replicate the findings of the studies that were done in Caucasians and other ethnic groups, ideally Genome-wide association studies. Presentation: Saturday, June 17, 2023