Work

The associations between CYP19A1 polymorphisms and serum 17ß‐estradiol levels in Chinese patients with Alzheimer’s disease

Year: 2024

Type: article

Abstract: BACKGROUND: Accumulating evidence has shown the neuroprotective effects of estrogen on cognition function, for example delaying the cognitive deterioration in patients with Alzheimer's disease (AD). However, the clinical usage of estrogen in AD remains controversial. The cytochrome P450 aromatase encoded by CYP19A1, is a key enzyme catalyzing the C19 androgen conversion to C18 estrogen, which induces testosterone to estradiol and androstenedione to estrone. The aromatase thus has been suggested to be an important partner of estrogen by controlling estrogen biosynthesis. Although increasing evidence has demonstrated the associations between CYP19A1 polymorphisms and AD susceptibility, previous studies are mainly carried out in Caucasian populations, little is known about the role of this gene and its impact on serum estrogen levels in Chinese population. METHOD: We recruited 689 subjects including both AD patients and non-demented controls in Hong Kong. Subjects' serum 17ß-estradiol were measured based on a chemiluminescent immunoassay principle. Genomic DNA was isolated from the whole blood and subsequent genotyping for 27 SNPs was analyzed on high-throughput Sequenom® genotyping platform according to the manufacturer's protocols. Statistical analysis was done using SPSS and PLINK. RESULT: After quality control, 3 SNPs were filtered and 24 SNPs spanning 122kb of this gene were included in data analysis. There was no significant difference for serum17ß-estradiol levels between AD patients and non-demented controls. The APOE ε4 allele was consistently associated with an increased AD risk (p<0.001). While the distribution of CYP19A1 polymorphisms was very similar between AD patients and non-demented controls and no significant differences were observed for each individual polymorphism in the sample. However, using multiple linear regression analyses, we found significant associations between 4 (rs2008691, rs1902586, rs7181886, and rs17647719) CYP19A1 polymorphisms with serum17ß-estradiol levels (p = 0.004, 0.039, 0.046 and 0.047, separately) after permutation by 10,000 times in Chinese population. CONCLUSION: In conclusion, our findings suggest a novel link between CYP19A1 polymorphisms and variation of serum 17ß-estradiol levels in Chinese elderly. This novel evidence may reflect inter-individual differences of estrogen exposure according to different CYP19A1 genotypes during aging and dementia process. Our findings may highlight a new perspective to understand the underlying mechanisms of AD.

Source: Alzheimer s & Dementia

DOI: 10.1002/alz.086088

Authors: Lu Hua Chen, Yan Hui Fan, You‐Qiang Song, Leung‐Wing Chu

Institutions: Hong Kong Polytechnic University, Chinese Academy of Sciences, University of Hong Kong

Language: English

Topic: Alzheimer's disease research and treatments

Subfield: Physiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,000