A genetic epidemiologic investigation of Latent Autoimmune Diabetes of Adults LADA from the selected endogamous ethnic groups of India

Abstract

Latent autoimmune diabetes of adults LADA is an autoimmune disorder characterized by slow beta cell failure despite the presence of diabetes associated autoantibodies Due to the no consensus diagnostic criteria and heterogenous phenotype of LADA it is often misdiagnosed hence it is important to determine the potential genetic markers to characterize the pathogenesis of LADA The study participants were 529 type 2 diabetes T2D individuals recruited from families of three different endogamous ethnic groups EEG Chettiyar CH Reddy RE and Agarwal AG The genetic association of LADA with 150 T2D susceptible SNPs were genotyped by RFLP Taqman allelic discrimination and Fluidigm technology The statistical analyses were carried out using SOLAR and SPSSv27 software The overall prevalence of LADA from three EEGs was found to be 76 percent with higher frequency in CH 94 percent AG 72 percent and RE 63 percent Clinical and metabolic analyses revealed significantly increased FBS PPBS HbA1c HDL levels and lower hip circumference in LADA compared to T2D GAD65 titers correlated with distinct metabolic profiles in LADA patients Heritability analysis indicated 40 percent heritability for GAD65 titers Interestingly genotyping of 150 T2D associated SNPs identified risk alleles of SIRT1 rs12778366 WFS1 rs10012946 MPHOSPH9 rs1727313 JPH2 rs73908569 significantly associated with the susceptibility of LADA Additionally SIRT1 rs12778366 JPH2 rs73908569 MASP1 rs3733001and ANPEP rs148567888 were linked to elevated GAD65 titers Thus this study reveals a high occurrence of LADA in the Indian EEGs and identified specific genetic markers with potential functional relevance that enhances the understanding of LADA pathogenesis newline