Association of TNF gene polymorphisms with cognitive aging in longevity populations

Objective: To explore the association between tumor necrosis factor (TNF) gene polymorphisms and cognitive aging in longevity areas of Guangxi. Methods: A total of 1,129 elderly Zhuang individuals (575 males, 554 females), aged over 60 years, from the Hongshui River Basin and Hezhou region in Guangxi were included. They were divided into the longevous elderly (93.56±3.53 years), offspring of the longevous elderly (68.40±4.81 years), local elderly controls (69.30±5.50 years), and non-local elderly controls (68.93±5.61 years). The participants' educational level, blood glucose, blood lipids, C-reactive protein (CRP) and other indicators were recorded. Cognitive status was assessed and defined by the mini-mental state examination (MMSE) in the study population. Genotyping of the TNF gene was performed using the SNPscan^TM multiplex single nucleotide polymorphism (SNP) genotyping assay. Haplotype analysis was conducted using Haploview 4.2 software. Statistical analyses were performed using SPSS software, including analysis of variance (ANOVA), t-test, chi-square test, and logistic regression analysis. Results: The offspring of the longevous elderly had significantly higher MMSE scores (25.56±3.07) than the local elderly controls and non-local elderly controls, and exhibited a lower cognitive impairment rate (11.0%) compared with the other two groups (P＜0.05). In the dominant genetic model of the longevous elderly, offspring of the longevous elderly, and local elderly controls, compared with the individuals carrying the TNF rs1799964 TT genotype, the individuals carrying the rs1799964 TC+CC genotype had a significantly reduced risk of cognitive impairment (P＜0.05). Compared with the individuals carrying the rs1800630_CC genotype, the individuals carrying the rs1800630 CA+AA genotype had a significantly lower risk of cognitive impairment (P＜0.05). In the allelic model, the individuals carrying the rs1800630_A allele showed a lower incidence of cognitive impairment than those carrying the C allele (OR=0.341, 0.311 and 0.457, respectively; P＜0.05). However, no association was found between the genotypes of rs1799964 and rs1800630 and cognitive function in the non-local elderly controls. Haplotype analysis revealed that the TNF C-A-C haplotype (rs1799964-rs1800630-rs1799724) was negatively correlated with the risk of cognitive impairment in the longevous elderly, offspring of the longevous elderly, and local elderly controls (OR=0.369, 0.313 and 0.452, respectively; all P＜0.05), whereas no such correlation was observed in the non-local elderly controls. Conclusion: In the population of the Hongshui River Basin in Guangxi, the direct offsprings of longevous individuals maintain relatively good cognitive function. The individuals carrying the TNF rs1799964_C and rs1800630_A alleles have a significantly reduced risk of cognitive impairment, serving as protective genetic factors against cognitive aging.