Oligodendrocyte Lineage Transcription Factor 2 role in Alzheimer's disease: association and expression analysis

Background: Oligodendrocyte Lineage Transcription Factor 2 (OLIG2) is a helix-loop-helix transcriptional factor. It is expressed both in the developing and in the mature vertebrate central nervous system. Recently studies identified OLIG2 as a candidate gene for schizophrenia and psychotic symptoms, which can occur also in patients with Alzheimer’s disease (AD). Aims and methods: To carry out an association study of OLIG2 rs1005573 (T/C) and rs2834072 (A/G) by allelic discrimination in a population of 348 patients with AD and 326 age-matched controls. To perform an expression study of OLIG2 in Peripheral Blood Mononuclear Cells (PBMC). Results: The frequency of the rs1005573 C allele was significantly increased in patients as compared with controls (40% versus 31%; p = 0.015; OR: 1.48; CI 95%: 1.09–2.02). Stratifying according to gender, a statistically significant difference was observed in female patients as compared with female controls (42% versus 33%: p = 0.007; OR: 1.76; CI 95%: 1.19–2.62), but not in males (p > 0.05). Conversely,we didn’t observe any differences stratifying according to age at onset (early/late). No differences in the distribution of rs2834072 between cases and controls were found. Significantly decreased relative expression levels of OLIG2 inPBMCwas observed in patients versus controls. Patients carrying the rs1005573 C allele displayed an even lower expression rate than non-carriers (0.101±0.067 vs 0.911±0.203; p = 0.001). Conclusions: rs1005573 variant is a risk factor for Alzheimer, and acts by regulating OLIG2 mRNA levels.