MAY 12, 2016 7:30 AM PDT

Polymorphic miRNA binding sites in the WFS1 gene are risk factors of diabetes mellitus

Speaker

Abstract

     Wolframin is a major protein of the endoplasmic reticulum, it is expressed in most tissues and clinical data demonstrate its significant connection to diabetes mellitus. Loss of function mutations of the WFS1 gene result in the monogenic Wolfram-syndrome, characterized by optic atrophy, diabetes insipidus, early onset diabetes mellitus and deafness. Accordingly, polymorphic variants of the gene, which cause only minor alterations in protein function, are putative risk factors of diabetes. This presentation focuses on the association and molecular analysis of two SNPs (rs1046322 and rs9457) in the 3’ UTR region of the WFS1 gene, which are supposed to alter the binding of miRNA-668 and miRNA-185, respectively, based on in-silico data.

     Association analysis of the polymorphic loci and diabetes mellitus was carried out on 617 patients and 1147 health controls in the study. Genotype analysis was carried out using PCR and single base extension (SBE) reaction using the GenomeLab GeXP™ Genetic Analyzer. Functional analysis of miRNA binding was investigated by luciferase reporter system.  The results suggested that rs9457 SNP “C” allele was significantly more frequent among patients with type 2 diabetes mellitus (p = 0.0008), whereas the rs1046322 variant showed a significant association with the type 1 form of the disease. Haplotype analysis confirmed the roles of the polymorphic variants in the genetic background of diabetes. In addition, the luciferase reporter experiments confirmed the data of the sequence analysis in where the rs1046322 and the rs9457 SNPs altered the binding of miRNA-668 and miRNA-185, respectively. Earlier studies indicated an association between a third variant of the 3’ UTR (rs1046320) and diabetes; however no biological function of the SNP could be observed. This is probably due to the strong linkage disequilibrium between rs9457 and rs1046322, thus the latter polymorphism could be a potential genetic marker of rs9457 miRNA-SNP.


Show Resources
You May Also Like
SEP 14, 2021 7:00 AM PDT
C.E. CREDITS
SEP 14, 2021 7:00 AM PDT
Date: September 14, 2021 Time: 7am PDT, 10am EDT, 4pm CEST A conventional thermal cycler has long been a commodity product in the lab and end-point PCR techniques can be completed almost wit...
MAY 11, 2021 10:00 AM PDT
C.E. CREDITS
MAY 11, 2021 10:00 AM PDT
Date: May 11, 2021 Time: 10:00zm PDT Your samples are some of the most valuable assets in the laboratory. After spending countless hours on extraction and preparation, your conclusions could...
SEP 17, 2021 12:00 PM CST
C.E. CREDITS
SEP 17, 2021 12:00 PM CST
Date: September 16, 2021 Time: 9:00pm (PDT), 12:00am (EDT) 3D cellular models like organoids and spheroids offer an opportunity to better understand complex biology in a physiologically rele...
JUN 09, 2021 7:00 AM PDT
C.E. CREDITS
JUN 09, 2021 7:00 AM PDT
Date: June 9, 2021 Time: 09 June 2021, 7am PDT, 10am EDT, 4pm CEST cells with dramatic implications on the validity of past cell culture related research. The fact that at least 509 cell lin...
OCT 20, 2021 10:00 AM PDT
C.E. CREDITS
OCT 20, 2021 10:00 AM PDT
Date: October 20, 2021 Time:10:00am (PDT), 1:00pm (EDT) As the prevalence of Diabetes continues to rise in many areas across the globe, healthcare providers continue to look for methods that...
MAY 18, 2021 7:00 AM PDT
MAY 18, 2021 7:00 AM PDT
Date: May 18, 2021 Time: 7:00am PDT, 10:00am EDT Proteins encoded by mutant genes in cancers can be processed and presented on tumor cell surface by human leukocyte antigen (HLA) molecules,...
MAY 12, 2016 7:30 AM PDT

Polymorphic miRNA binding sites in the WFS1 gene are risk factors of diabetes mellitus


Specialty

Research And Development

Earth Science

University

Research

Health

Geography

Asia100%

Registration Source

Website Visitors100%

Job Title

Medical Laboratory Technician100%

Organization

Manufacturer - Other100%


Show Resources
Loading Comments...
Show Resources