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PMID 30502936
Gene Name HLA-B
Condition Non-obstructive azoospermia
Association Associated
Mutation rs4997052
Population size 2638
Population details 2638 (981 men with NOA and 1,657 normal fertile male controls)
Sex Male
Infertility type Male infertility
Associated genes GWAS


Fine mapping the MHC region identified rs4997052 as a new variant associated with nonobstructive azoospermia in Han Chinese males

Huang M, Zhu M, Jiang T, Wang Y, Wang C, Jin G, Guo X, Sha J, Dai J, Wang X, Hu Z.

OBJECTIVE: To investigate the association between genetic variants in the major histocompatibility complex (MHC) region and nonobstructive azoospermia (NOA) susceptibility. DESIGN: MHC region fine-mapping analysis based on previous NOA genome-wide association study (GWAS) data. SETTING: Medical university. PATIENT(S): Nine hundred and eighty-one men with NOA and 1,657 normal fertile male controls. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The MHC region imputation assessed with SNP2HLA software, taking the specific Han-MHC database as a reference panel; statistical significance of the MHC variants calculated using logistic regression models; functional annotation based on online public databases; and phenotypic variances explained by specific groups of genetic variants estimated using the fixed effects model from individual associations. RESULT(S): Two independent risk loci, rs7194 (odds ratio [OR] 1.37) at MHC class II molecules and rs4997052 (OR 1.30) at MHC class I molecules, were identified. Functional annotation showed rs7194 may tag the effect of multiple amino acid residues and the expression of HLA-DQB1 and HLA-DRB1; while rs4997052 showed the effect of amino acid changes of HLA-B at position 116 as well as the expression of HLA-B and CCHCR1, which coexpressed with genes enriched in pathways of spermatogenesis and male gamete generation. The novel variant rs4997052 identified in our study can explain another approximately 0.66% of the phenotypic variances of NOA. CONCLUSION(S): We fine-mapped the MHC region and identified two loci that independently drove NOA susceptibility. These results provide a deeper understanding of the association mechanisms of MHC and NOA risk. CI - Copyright © 2018 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved. FAU - Huang, Mingtao AU - Huang M AD - Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China; Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China. FAU - Zhu, Meng AU - Zhu M AD - Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China; Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China. FAU - Jiang, Tingting AU - Jiang T AD - Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China; Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China; State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, People's Republic of China. FAU - Wang, Yifeng AU - Wang Y AD - Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China; Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China; State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, People's Republic of China. FAU - Wang, Cheng AU - Wang C AD - Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China; Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China. FAU - Jin, Guangfu AU - Jin G AD - Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China; Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China; State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, People's Republic of China. FAU - Guo, Xuejiang AU - Guo X AD - State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, People's Republic of China. FAU - Sha, Jiahao AU - Sha J AD - State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, People's Republic of China. FAU - Dai, Juncheng AU - Dai J AD - Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China; Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China. FAU - Wang, Xiaoming AU - Wang X AD - State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, People's Republic of China.