Adiponectin Gene Polymorphisms: A Case-Control Study on Their Role in Late-Onset Alzheimer's Disease Risk

Abstract

Adiponectin, a hormone secreted by adipose tissue, plays a complex role in regulating metabolic homeostasis and has also garnered attention for its potential involvement in the pathogenesis of late-onset Alzheimer's disease (LOAD). The objective of this study was to investigate the association of ADIPOQ variants with plasma adiponectin levels and LOAD risk in subjects from the Slovak Caucasian population. For this purpose, 385 LOAD patients and 533 controls without cognitive impairment were recruited and genotyped for a total of eighteen ADIPOQ single nucleotide polymorphisms (SNPs). Both single-locus and haplotype-based logistic regression analyses were employed to assess the association of SNPs with LOAD risk, while linear regression analysis was used to explore their influence on adiponectin levels in LOAD patients. ADIPOQ variants rs822395 and rs2036373 in intron 1 were found to significantly elevate total adiponectin levels after accounting for several potential confounders. Additional SNPs in the 5' region and intron 1 exhibited a non-significant trend of association with adiponectin. However, none of the ADIPOQ SNPs showed an association with LOAD risk, neither in the whole-group analysis nor in subgroup analyses after stratification for sex or the APOE ε4 allele, a well-established LOAD risk factor. In summary, while adiponectin has emerged as a potential contributor to the development of LOAD, this study did not unveil any significant involvement of its gene variants in susceptibility to the disease.

Keywords: ADIPOQ; Alzheimer’s disease; adiponectin; association; single nucleotide polymorphism; susceptibility.

Figure 1

Gene map of ADIPOQ with the linkage disequilibrium (LD) plot for all SNPs genotyped in Slovak subjects. The upper part of the figure illustrates the structure of the ADIPOQ gene with the location of SNPs on a physical scale. LD plots and haplotype blocks were constructed with the Haploview version 4.2 software. The different colors and shadings in the LD plot represent the magnitude and significance of pairwise LD. Diamonds in the darkest shade indicate the highest LD (D’ = 1 and the logarithm of odds [LOD] ≥ 2) between two SNPs, with the color intensity decreasing with decreasing D’ value. White color indicates D’ value ˂ 1 with LOD score ˂ 2, while grey-blue color corresponds to D’ = 1 and LOD ˂ 2. The number within each diamond indicates the exact r² pairwise correlation value multiplied by 100.