engleski

The association of TSH and thyroid hormones with APOE genotype

The scope of this study was to investigate if APOE (apolipoprotein E) genotype affects thyroid stimulating hormone (TSH) and thyroid hormone levels. APOE is the main genetic risk factor for development of sporadic Alzheimer’s disease (AD) (with ε4, ε2 and ε3 as risk, protective and the most common allele, respectively). A recent study showed the association between serum TSH levels and AD pathology, with TSH levels being positively correlated and fT4 levels negatively correlated with cerebral amyloid β burden. However, the other study showed that higher thyroid function (with lower TSH levels and higher fT3 levels) was associated with greater annual hippocampal volume loss. Additionally, it was shown that APOE ε4 genotype is the risk factor for foetal iodine deficiency syndrome. In fact, APOE protein possesses a thyroid hormone binding domain and triiodothyronine (T3) can affect APOE gene expression. In this study, we included 2701 cognitively healthy individuals with determined APOE haplotype, TSH, and thyroid hormone levels (fT3, fT4). We found no signifcant change in TSH and thyroid hormone levels between carriers of different APOE genotype. However, after subgroup analysis (according to the age and gender), we observed a signifcant decrease in fT3 levels in carriers of APOE ε4 risk allele (p = 0.039 ; in males younger than 65 years). Interestingly, in the individuals older than 65 years carrying protective APOE ε2 allele, we also observed a decrease in fT3 (p = 0.034) and fT4 levels (p = 0.012). In males older than 65 years carrying risk APOE ε4 allele we observed the decrease in TSH levels (p = 0.003). Our results did not depict the clear relationship between thyroid hormones and APOE genotype since conflicting results were observed in older and younger participants. However, these results indicate that the possible involvement of TSH and thyroid hormones in AD pathology deserves further investigation.

Alzheimer's disease ; APOE genotype ; thyroid stimulating hormone ; thyroid hormone levels

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