Endocrine Abstracts

Background: Diabetes mellitus is the commonest endocrinopathy, Worldwide. Inspite of its commonality, the genetic basis of etiopathogenesis and pathophysiology are ever evolving and enigmatic. Amongst the protean 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 analysed the prevalence of cubulin (CBN) and megalin (LRP2) gene mutations in diabetes patients visavis controls.

Methods: This is inter-disciplinary case control study conducted by collaboration between a tertiary care endocrinology hospital, biochemistry department of a teaching medical institute and genetics lab. In this prospective study, we employed 4 sets of primers and screened for cubulin; CUBN gene polymorphisms (rs1801222 and rs11254363) and megalin (LRP2) gene polymorphisms (rs3755166 and rs2544390). in subjects with type 2 diabetes mellitus.

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 for CUBN gene and non-significant for LRP2 gene.

Conclusions: For cubulin gene, the AA genotype along with the A allele showed an odds ratio value of 0.06 and 0.19 respectively. The AG and G allele demonstrated 7.5-fold and 5.5-fold risk. For LRP2 gene, none of the genotypes showed a protective or predisposing role.

Keywords: diabetes, cubulin gene, megalin gene, polymorphism.