J 2023

Evaluation of genetic risk, its clinical manifestation and disease management based on 18 susceptibility gene markers among West-Slavonic patients with sarcoidosis

KISHORE, Amit, Katerina SIKOROVA, Lenka KOCOURKOVA, Jana PETRKOVA, Martina DOUBKOVÁ et. al.

Basic information

Original name

Evaluation of genetic risk, its clinical manifestation and disease management based on 18 susceptibility gene markers among West-Slavonic patients with sarcoidosis

Authors

KISHORE, Amit, Katerina SIKOROVA, Lenka KOCOURKOVA (203 Czech Republic), Jana PETRKOVA (203 Czech Republic), Martina DOUBKOVÁ (203 Czech Republic, belonging to the institution), Petr JAKUBEC (203 Czech Republic), Krzysztof REBALA, Anna DUBANIEWICZ and Martin PETREK (guarantor)

Edition

Gene, Amsterdam, Elsevier Science, 2023, 0378-1119

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30203 Respiratory systems

Country of publisher

Netherlands

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Impact factor

Impact factor: 3.500 in 2022

RIV identification code

RIV/00216224:14110/23:00131815

Organization unit

Faculty of Medicine

DOI

UT WoS

001036147700001

Keywords in English

Pulmonary sarcoidosis; Immune gene polymorphism; Lofgren's syndrome; Genetic susceptibility; West -Slavonic population

Tags

Tags

International impact, Reviewed
Změněno: 3/10/2023 08:52, Mgr. Tereza Miškechová

Abstract

V originále

Sarcoidosis is a heterogenous, multisystemic inflammatory disease that primarily affects lungs. In this study, we multiplex genotyped 18 single-nucleotide polymorphisms (SNPs) to replicate the findings from previous genome-wide association studies (GWAS) and candidate gene studies, and extended analyses to different clinical manifestations (Lofgren's syndrome and chest X-ray [CXR] stages) including treatment response among West-Slavonic subjects (564 sarcoidosis patients and 301 healthy controls). We confirm the replication (with Bonferroni's correction) of ANXA11 rs1049550 as protective variant for sarcoidosis (odds ratio [OR] = 0.71, p = 1.33 x 10(-3)), non-LS (OR = 0.66, p = 2.71 x 10(-4)) and CXR stages 2-4 (OR = 0.62, p = 7.48 x 10(-5)) compared to controls in West-Slavonic population. We also validate the association of risk variants C6orf10 rs3129927 (OR = 2.61, p = 2.60 x 10(-8)), TNFA rs1800629 (OR = 1.56, p = 6.65 x 10(-4)), ATF6B rs3130288 (OR = 2.75, p = 1.06 x 10(-9)) and HLA-DQA1 rs2187668 (OR = 1.74, p = 8.83 x 10(-4)) with sarcoidosis compared to controls. For sub -phenotypes compared to controls, risk variants C6orf10 rs3129927 (OR = 5.35, p = 1.07 x 10(-12)), TNFA rs1800629 (OR = 2.66, p = 5.94 x 10(-7)), ATF6B rs3130288 (OR = 5.24, p = 5.21 x 10(-13)), LRRC16A rs9295661 (OR = 2.97, p = 4.29 x 10(-4)), HLA-DQA1 rs2187668 (OR = 3.14, p = 1.09 x 10(-6)) and HLA-DRA rs3135394 (OR = 5.23, p = 8.25 x 10(-13)) were associated with LS while C6orf10 rs3129927 (OR = 1.96, p = 4.27 x 10(-4)) and ATF6B rs3130288 (OR = 2.15, p = 3.36 x 10(-5)) were associated with non-LS. For CXR stages compared to controls, C6orf10 rs3129927 (OR = 3.67, p = 3.63 x 10(-11)), TNFA rs1800629 (OR = 1.84, p = 1.32 x 10(-4)), ATF6B rs3129927 (OR = 3.63, p = 1.82 x 10(-11)), HLA-DQA1 rs2187668 (OR = 2.13, p = 9.59 x 10(-5)) and HLA-DRA rs3135394 (OR = 3.42, p = 3.45 x 10(-10)) were risk variants for early CXR stages 0-1 while C6orf10 rs3129927 (OR = 1.99, p = 5.51 x 10(-4)), ATF6B rs3129927 (OR = 2.23, p = 3.52 x 10(-5)) and HLA-DRA rs3135394 (OR = 1.85, p = 2.00 x 10(-3)) were risk variants for advanced CXR stages 2-4. The present findings nominate gene variants as plausible prognostic markers for clinical phenotypes, treatment response and disease resolution/progression and may form the basis for establishing genotype-phenotype relationships in patients with sarcoidosis among West-Slavonic population.