Role of hnRNP-A1 and miR-590-3p in neuronal death: genetics and expression analysis in patients with Alzheimer disease and frontotemporal lobar degeneration

Rejuvenation Res. 2011 Jun;14(3):275-81. doi: 10.1089/rej.2010.1123. Epub 2011 May 6.

Abstract

An association study of heterogeneous nuclear ribonucleoprotein (hnRNP)-A1 was carried out in a population of 274 patients with frontotemporal lobar degeneration (FTLD) and 287 with Alzheimer disease (AD) as compared with 344 age- and gender-matched controls. In addition, we evaluated expression levels of hnRNP-A1 and its regulatory microRNA (miR)-590-3p in blood cells from patients and controls. A statistically significant increased frequency of the hnRNP-A1 rs7967622 C/C genotype was observed in FTLD, but not in AD, in patients as compared to controls (23.0 versus 15.4%; p = 0.022, odds ratio [OR] 1.64, confidence interval [CI] 1.09-2.46). Stratifying according to gender, a statistically significant increased frequency of the hnRNP-A1 rs7967622 C/C genotype was observed in male patients as compared to male controls (23.1 versus 11.3%; p = 0.015, OR 2.36, CI 1.22-4.58 but not in females. Considering the rs4016671 single-nucleotide polymorphism (SNP), all patients and controls were wild type. Significantly increased hnRNP-A1 relative expression levels in peripheral blood mononuclear cells (PBMCs) was observed in patients with AD, but not with FTLD, as compared to controls (2.724 ± 0.570 versus 1.076 ± 0.187, p = 0.021). Decreased relative expression levels of hsa-miR-590-3p was observed in patients with AD versus controls (0.685 ± 0.080 versus 0.931 ± 0.111, p = 0.079), and correlated negatively with hnRNP-A1 mRNA levels (r = -0.615, p = 0.0237). According to these findings, hnRNP-A1 and its transcription regulatory factor miR-590-3p are disregulated in patients with AD, and the hnRNP-A1 rs7967622 C/C genotype is likely a risk factor for FTLD in male populations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alleles
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / pathology
  • Base Sequence
  • Case-Control Studies
  • Cell Death
  • Female
  • Frontotemporal Lobar Degeneration / genetics*
  • Frontotemporal Lobar Degeneration / pathology
  • Gene Expression Regulation*
  • Gene Frequency / genetics
  • Heterogeneous Nuclear Ribonucleoprotein A1
  • Heterogeneous-Nuclear Ribonucleoprotein Group A-B / blood
  • Heterogeneous-Nuclear Ribonucleoprotein Group A-B / genetics*
  • Humans
  • Male
  • MicroRNAs / blood
  • MicroRNAs / genetics*
  • Molecular Sequence Data
  • Neurons / metabolism*
  • Neurons / pathology*
  • Polymorphism, Single Nucleotide / genetics
  • Sequence Alignment

Substances

  • Heterogeneous Nuclear Ribonucleoprotein A1
  • Heterogeneous-Nuclear Ribonucleoprotein Group A-B
  • MIRN590 microRNA, human
  • MicroRNAs