CAPN10 mRNA splicing and decay is not affected by a SNP associated with susceptibility to type 2 diabetes

• Published in: Biochemical and biophysical research communications Vol. 358; no. 3; pp. 831 - 836
• Main Authors: López-Orduña, Eduardo, García-Mena, Jaime, García-Macedo, Rebeca, Stumvoll, Michael, Cruz, Miguel
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 06.07.2007
• Subjects: Adult; Alleles; Calpain - genetics; Calpain - metabolism; CAPN10; Diabetes Mellitus, Type 2 - genetics; Diabetes Mellitus, Type 2 - metabolism; Female; Genetic Predisposition to Disease; Genotype; Humans; Jurkat Cells; Male; Messenger RNA; Middle Aged; mRNA decay; Polymorphism, Single Nucleotide; RNA Precursors - metabolism; RNA Splicing; RNA, Messenger - metabolism; Single nucleotide polymorphism; Type 2 diabetes; Type 2 diabetes; Messenger RNA; Single nucleotide polymorphism; CAPN10; mRNA decay
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2007.05.001

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 8 h. 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.