%0 Journal Article
%T Interactions of genetic variations in FAS, GJB2 and PTPRN2 are associated with noise-induced hearing loss: a case-control study in China.
%A Wu S
%A Wu Z
%A Chen M
%A Zhong X
%A Gu H
%A Du W
%A Liu W
%A Lang L
%A Wang J
%J BMC Med Genomics
%V 17
%N 1
%D 2024 Jan 11
%M 38212800
%F 3.622
%R 10.1186/s12920-023-01790-7
%X <B>BACKGROUND: </B>This study aimed to screen and validate noise-induced hearing loss (NIHL) associated single nucleotide polymorphisms (SNPs), construct genetic risk prediction models, and evaluate higher-order gene-gene, gene-environment interactions for NIHL in Chinese population.<BR><B>METHODS: </B>First, 83 cases and 83 controls were recruited and 60 candidate SNPs were genotyped. Then SNPs with promising results were validated in another case-control study (153 cases and 252 controls). NIHL-associated SNPs were identified by logistic regression analysis, and a genetic risk model was constructed based on the genetic risk score (GRS), and classification and regression tree (CART) analysis was used to evaluate interactions among gene-gene and gene-environment.<BR><B>RESULTS: </B>Six SNPs in five genes were significantly associated with NIHL risk (p < 0.05). A positive dose-response relationship was found between GRS values and NIHL risk. CART analysis indicated that strongest interaction was among subjects with age ≥ 45 years and cumulative noise exposure ≥ 95 [dB(A)·years], without personal protective equipment, and carried GJB2 rs3751385 (AA/AB) and FAS rs1468063 (AA/AB) (OR = 10.038, 95% CI = 2.770, 47.792), compared with the referent group. CDH23, FAS, GJB2, PTPRN2 and SIK3 may be NIHL susceptibility genes.<BR><B>CONCLUSIONS: </B>GRS values may be utilized in the evaluation of the cumulative effect of genetic risk for NIHL based on NIHL-associated SNPs. Gene-gene, gene-environment interaction patterns play an important role in the incidence of NIHL.