IGF2 ApaI A/G Polymorphism Evaluated in ESRD Individuals as a Biomarker to Identify Patients with New Onset Diabetes Mellitus after Renal Transplant in Asian Indians

Insulin like growth factors2 (IGF2) regulates pancreatic β-cell renewal and apoptosis, which in turn plays a role in altering insulin activity and glucose homeostasis. Polymorphisms in IGF2 gene have been associated with altered levels of IGF2. Hence, ApaI polymorphism in exon 9 of IGF2 (rs#680) gene was assessed in patients with end stage renal disease (ESRD) to identify individuals at risk of developing new onset diabetes mellitus (NODM) in Asian Indians. Isolated DNA was used for PCR&RFLP based genotyping of IGF2 ApaI polymorphism which was carried out in 364 individuals these included 140 patients who had undergone renal transplant, 42 of which developed new onset diabetes mellitus after renal transplant and 224 healthy control volunteers. In the present study NODM or post transplant diabetes mellitus (PTDM) showed a significant association with G allele and AG genotype when compared with the Non-NODM ESRD patients after transplant (OR 2.081, 95% CI = 1.191 - 3.634, p = 0.01 and OR 3.188, 95% CI = 1.498 - 6.785, p = 0.002) ESRD patients with healthy controls also showed an association with G allele and AG genotype (OR 1.512, 95% CI = 1.060 - 2.155, p = 0.02 and OR 2.235, 95% CI = 1.453 - 3.438, p = 0.0002). IGF2 could be used as a biomarker to identify individuals at high risk of developing NODM, it would be a valuable asset in selecting appropriate immunosuppressive regimens for individuals undergoing transplant. Present study shows the importance of IGF2 ApaI polymorphism in assessing the risk of NODM in ESRD individuals in Asian Indians with ESRD.

Chromosome 11 aneusomy in esophageal cancers and precancerous lesions-an early event in neoplastic transformation:An interphase fluorescence in situ hybridization study from south India

AIM: To detect aneusomic changes with respect to chromosome 11 copy number in esophageal precancers and cancers wherein the generation of cancer-specific phenotypes is believed to be associated with specific chromosomal aneuploidies. METHODS: We performed fluorescence in situ hybridization (FISH) on esophageal tissue paraffin sections to analyze changes in chromosome 11 copy number using apotome-generated images by optical sectioning microscopy. Sections were prepared from esophageal tumor tissue, tissues showing preneoplastic changes and histologically normal tissues (control) obtained from patients referred to the clinic for endoscopic evaluation. RESULTS: Our results demonstrated that aneusomy was seen in all the cancers and preneoplastic tissues, while none of the controls showed aneusomic cells. There was no increase in aneusomy from precancers to cancers. CONCLUSION: Our results suggest that evaluation of chromosome 11 aneusomy in esophageal tissue using FISH with an appropriate signal capture-analysis system, can be used as an ancillary molecular marker predictive of early neoplastic changes. Future studies can be directed towards the genes on chromosome 11,which may play a role in the neoplastic transformation of esophageal precancerous lesions to cancers.

Correlation between KCNQ1 and KCNJ11 gene polymorphisms and type 2 and posttransplant diabetes mellitus in the Asian Indian population

Type 2 diabetes mellitus(T2DM)and post-transplant diabetes mellitus(PTDM)share a common pathophysiology.However,diabetes mellitus is a complex disease,and T2DM and PTDM have different etiologies.T2DM is a metabolic disorder,characterized by persistent hyperglycemia,whereas PTDM is a condition of abnormal glucose tolerance,with variable onset after organ transplant.The KCNQ1 and KCNJ11 gene encode potassium channels,which mediate insulin secretion from pancreatic b-cells,and KCN gene mutations are correlated with the development of diabetes.However,no studies have been carried out to establish an association between KCNQ1 and KCNJ11 gene polymorphisms and T2DM and PTDM.Therefore,our study was aimed at the identification of the role of KCNQ1 and KCNJ11 gene polymorphisms associated with T2DM and the risk of developing PTDM in the Asian Indian population.We have carried out a caseecontrol study including 250 patients with T2DM,250 control subjects,42 patients with PTDM and 98 subjects with non-PTDM.PCR-RFLP analysis was carried out following the isolation of genomic DNA from EDTA-blood samples.The results of the present study reveal that two single nucleotide polymorphisms(rs2283228 and rs5210,of the KCNQ1 and KCNJ11 genes,respectively)are associated with both T2DM and PTDM.The results of our study suggest a role of KCNQ1 and KCNJ11 gene variants in the increased risk of T2DM and PTDM in the Asian Indian population.