Endocrine Abstracts

Background: Diabetes mellitus (DM) is the commonest endocrinopathy, Worldwide. Amongst the protean complex genetic variations, cubulin gene and megalin gene mutations in diabetes are important in dictating genotype-phenotypic correlations and natural clinical course of diabetes. The genetic studies in this area are especially very sparse from Indian sub-continent. In this context, we analyzed the prevalence of cubulin (CBN) and megalin (LRP2) gene mutations, as part of NGS (Next-generations sequencing) in diabetes patient’s visavis controls.

Methods: This is inter-disciplinary case control study conducted by collaboration between biochemistry department of a teaching medical institute, a tertiary care endocrinology hospital, and genetics lab. Institutional ethical committee approval was obtained. In this prospective study, CUBN gene polymorphisms and megalin (LRP2) gene polymorphisms in subjects with type 2 diabetes mellitus using real-time PCR and ThyroSeq v2 on the Ion Torrent PGM sequencer was employed. Mutations were also manually checked using the Integrated Genomics Viewer v2.4.10 to filter out false positives.

Results: The percentages of AA, AG and GG in cases were 12.5, 62.5 and 25 while in controls it was 70, 20 and 10 respectively. The allele frequencies of A and G alleles in patients are 0.44 and 0.56, while in controls were 0.80 and 0.20 correspondingly. The percentages of CC, CT and TT in cases were 47.5, 50 and 2.5 while in controls it was 60, 30 and 10 respectively. The allele frequencies of A and G alleles in patients are 0.73 and 0.27 while in controls were 0.75 and 0.25 correspondingly. The difference was statistically significant (P -value <0.05) for CUBN gene and non-significant for LRP2 gene.

Conclusions: The rs622342 polymorphism of SLC22A1 appears to be the commonest mutation in South Indian T2DM patients. Cubulin gene mutation was significantly and megalin gene was insignificantly associated with DM. However, it needs validation in larger cohort studies through assessing the additional variants of SLC22A1 gene at the mRNA levels. NGS helps in patient management, providing risk stratification and sub-classification of DM.