We carried out an association study of transmembrane protein 106B gene (TMEM106B) rs1020004 A/G, rs6966915C/T, and rs1990622 A/G in a population of 656 patients with Alzheimer's disease (AD) and 619 ...controls, and tested whether the rs1990622 influences plasma progranulin levels. No differences in allele and genotype distribution were observed between cases and controls, even stratifying according to APOE status (p > 0.05). No differences in progranulin plasma levels were found between carriers of the rs1990622 and non-carriers. TMEM106b variability does not influence AD risk or plasma levels. Replication, preferably in a population with pathological confirmation, is required to confirm these results.
Transcription factor Sp4 (Specificity protein 4) levels are increased in the brain of patients with Alzheimer's disease (AD), and Sp4 colocalizes with neurofibrillary tangles. Moreover, SP4 is a ...susceptibility gene for bipolar disorder and schizophrenia, which share many clinical features with frontotemporal lobar degeneration (FTLD). The distribution of three tagging single nucleotide polymorphisms(SNPs)-rs9639379, rs10272006, and rs6461569-has been determined in a population of 352 patients diagnosed clinically with AD, 290 patients with FTLD, and 341 age-matched controls. Expression analysis of SP4 was performed in peripheral blood mononuclear cells (PBMC). No significant differences in either allelic or genotypic frequency of the three SNPs were found (p > 0.05), even stratifying according to gender and to the apolipoprotein E status. Significantly increased SP4 relative expression levels were observed in PBMC from patients with AD as compared with controls (7.132 ± 1.301 versus 3.396 ± 0.829, p < 0.050) and a similar trend was shown in patients with FTLD compared with controls (6.525 ± 1.500 versus 3.396 ± 0.829, p = 0.073). According to these results, SP4 gene does not act as a susceptibility factor either for AD or FTLD. However, Sp4 mRNA levels are upregulated in patients, possibly resulting in an aberrant expression of downstream target genes involved in the pathogenesis of both diseases.
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