CAPN10 mRNA splicing and decay is not affected by a SNP associated with susceptibility to type 2 diabetes.
The mRNA concentration of CAPN10, a T2D susceptibility gene was measured in white blood cells of T2D and healthy subjects, as well as the transcript half-life in two SNP-43 genotyped human cell lines, to evaluate a possible relationship between this SNP-43 and the transcript half-life. T2D patients with the SNP-43 G-allele had 4.6-fold more CAPN10 transcripts compared to subjects with the A-allele. The mRNA half-life of this transcript in 293T cells (SNP-43 G/G) and Jurkat cells (SNP-43 A/A) was of 8h. We provide evidence that in T2D subjects the G-allele increases the CAPN10 mRNA levels. We propose a defective CAPN10 pre-mRNA processing is responsible for the decreased levels of SNP-43 A-allele transcripts in peripheral white cells of healthy and T2D individuals.
López-Orduña
Eduardo
E
Departamento de Genética y Biología Molecular, Cinvestav-IPN, Apartado Postal 14-740, Mexico DF 07360, Mexico.
García-Mena
Jaime
J
García-Macedo
Rebeca
R
Stumvoll
Michael
M
Cruz
Miguel
M
D000328:Adult; D000483:Alleles; D002154:Calpain / Q000235:genetics* / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D019169:Jurkat Cells; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012322:RNA Precursors / Q000378:metabolism; D012326:RNA Splicing; D012333:RNA, Messenger / Q000378:metabolism
D012322:RNA Precursors; D012333:RNA, Messenger; D002154:Calpain; C415197:calpain 10