Association study about genetic variants of inflammation-linked genes and dementia in the very old: The Monzino 80-plus Study

Abstract

Population aging is a positive outcome but aging-associated pathologies are becoming a serious social and sanitary burden. Inflammation is a main feature of neurodegeneration and it might contribute to the onset and progression of the pathology. The predisposing role to dementia of single nucleotide polymorphisms (SNPs) in pro-inflammatory genes as interleukin-1 alpha (IL-1α), beta (IL-1β) and tumor necrosis factor alpha (TNF-α) is controversial and has been explored mostly in Alzheimer's Disease (AD) with conflicting results. Significant data about the frequency of these polymorphisms in the very old population are lacking. Data were collected in a prospective, door-to-door population-based study of all eighty years or older residents in eight municipalities of Varese province, Italy (the Monzino 80-plus Study). Diagnosis of dementia was based on DSM-IV criteria. Participants that gave their consent for genetic screening (n = 516) were evaluated by means of a blood withdrawal that allowed genomic DNA extraction (gDNA) for genetic testing. IL-1α rs1800587 (C/T), IL-1β rs3087258 (C/T) and TNF-α rs1799724 (C/T) SNP genotyping was performed by Restriction Fragment Length Polymorphism (RFLP). The population examined for genetic testing had a mean age at baseline of 87.2 ± 3.8 years and male:female proportion was 1:3. Around 33% of subjects were diagnosed as demented at baseline. The mean Mini Mental State Examination (MMSE) of non demented and demented people was 25.7 ± 3.4 and 15.1 ± 4.0, respectively. In the non demented group, the IL-1α T allele showed a frequency of 25.1%, while in the demented group had a frequency of 25.5 %. The IL-1β T-allele frequency was 35.9 % in non demented people and 32.2 % in the demented group. Finally, frequency of TNF-α T allele was 21.5 % and 24.0 % in the non demented and demented groups, respectively. None of these differences was statistically significant (p >0.18). Our genetic investigation found no evidence that in this very old Italian population dementia is associated to the genetic variability in three polymorphisms mapping on IL-1α, IL-1β and TNF-α genes.