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, Petr JAKUBEC, Krzysztof REBALA, Anna DUBANIEWICZ and Martin PETREK. Evaluation of genetic risk, its clinical manifestation and disease management based on 18 susceptibility gene markers among West-Slavonic patients with sarcoidosis. Gene. Amsterdam: Elsevier Science, 2023, vol. 878, August 2023, p. 1-11. ISSN 0378-1119. Available from: https://dx.doi.org/10.1016/j.gene.2023.147577.

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

• Original language: English
• Type of outcome: Article in a journal
• Field of Study: 30203 Respiratory systems
• Country of publisher: Netherlands
• Confidentiality degree: is not subject to a state or trade secret
• WWW: URL
• Impact factor: Impact factor: 3.500 in 2022
• RIV identification code: RIV/00216224:14110/23:00131815
• Organization unit: Faculty of Medicine
• Doi: http://dx.doi.org/10.1016/j.gene.2023.147577
• UT WoS: 001036147700001
• Keywords in English: Pulmonary sarcoidosis; Immune gene polymorphism; Lofgren's syndrome; Genetic susceptibility; West -Slavonic population
• Tags: 14110215, rivok
• Tags: International impact, Reviewed

Abstract

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.