Influence of CYP3A4, CYP3A5, and NR3C1 genes polymorphism on the effectiveness of glucocorticoid therapy in patients with endocrine ophthalmopathy

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For more than 60 years, glucocorticoid therapy has been practically the only method for treating patients with endocrine ophthalmopathy — non-specific autoimmune inflammation of the soft tissues of the orbit. Steroid-resistant forms of this disease are known to exist. The reasons for the formation of glucocorticoid resistance are not fully understood yet.

PURPOSE

To study the possibilities of pharmacogenetic testing for the polymorphism of the glucocorticoid receptor gene NR3C1 and cytochrome P450 in predicting the effectiveness of glucocorticoid therapy in patients with edematous exophthalmos — one of the clinical forms of endocrine ophthalmopathy.

MATERIAL AND METHODS

The results of glucocorticoid therapy were analyzed in 75 patients with different clinical forms of endocrine ophthalmopathy aged 27 to 84 years. All patients underwent standard ophthalmological examination, external examination of the eye with assessment of the state of periorbital tissues, determination of the shape and size of the palpebral fissure (vertical size), position of the eye in orbit, Hertel exophthalmometry, ultrasound scanning and computed tomography of the orbits. Genetic analysis of the polymorphism of the studied genes was carried out using real-time polymerase chain reaction (real-time PCR).

RESULTS

The study did not find patterns in the distribution of homo- and heterozygous genotypes of A6986G polymorphic markers of the CYP3A5 gene, 6 C>T intron of the CYP3A4 gene and rs6190 of the NR3C1 gene in patients with endocrine ophthalmopathy and their effect on the glucocorticoid response (p>0.05).

CONCLUSION

Results of pharmacogenetic testing of the gene for the glucocorticoid receptor NR3C1 and cytochrome P450 do not provide a reliable confirmation of the influence of the polymorphism of the studied genes on the effectiveness of glucocorticoid therapy in patients with endocrine ophthalmopathy.

Keywords:

endocrine ophthalmopathy

glucocorticoid therapy

glucocorticoid receptor gene polymorphism

cytochrome P450 system

resistance

Authors:

A.F. Brovkina

Russian Medical Academy of Continuous Professional Education

D.A. Sychev

Russian Medical Academy of Continuous Professional Education

O.S. Toropova

Russian Medical Academy of Continuous Professional Education

Received:

23.05.2020

Accepted:

13.07.2020

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