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.

Základní údaje

Originální název

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

Autoři

KISHORE, Amit, Katerina SIKOROVA, Lenka KOCOURKOVA (203 Česká republika), Jana PETRKOVA (203 Česká republika), Martina DOUBKOVÁ (203 Česká republika, domácí), Petr JAKUBEC (203 Česká republika), Krzysztof REBALA, Anna DUBANIEWICZ a Martin PETREK (garant)

Vydání

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

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30203 Respiratory systems

Stát vydavatele

Nizozemské království

Utajení

není předmětem státního či obchodního tajemství

Odkazy

Impakt faktor

Impact factor: 3.500 v roce 2022

Kód RIV

RIV/00216224:14110/23:00131815

Organizační jednotka

Lékařská fakulta

DOI

UT WoS

001036147700001

Klíčová slova anglicky

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

Štítky

Příznaky

Mezinárodní význam, Recenzováno
Změněno: 3. 10. 2023 08:52, Mgr. Tereza Miškechová

Anotace

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.