Mingtao Huang, Meng Zhu, TingtingJiang, Yifeng Wang, Cheng Wang, Guangfu Jin, Xuejiang Guo, Jiahao Sha, Juncheng Dai, Xiaoming Wang, Zhibin Hu
Abstract
Objective: Toinvestigate the association between genetic variants in the majorhistocompatibility complex (MHC) region and nonobstructive azoospermia (NOA)susceptibility.
Design: MHCregion fine-mapping analysis based on previous NOA genome-wide associationstudy (GWAS) data.
Setting: Medicaluniversity.
Patient(s): Ninehundred and eighty-one men with NOA and 1,657 normal fertile male controls.
Intervention(s): None.
Mainoutcome measure(s): The MHC region imputation assessed with SNP2HLAsoftware, taking the specific Han-MHC database as a reference panel;statistical significance of the MHC variants calculated using logisticregression models; functional annotation based on online public databases; andphenotypic variances explained by specific groups of genetic variants estimatedusing the fixed effects model from individual associations.
Result(s): Twoindependent risk loci, rs7194 (odds ratio [OR] 1.37) at MHC class II moleculesand rs4997052 (OR 1.30) at MHC class I molecules, were identified. Functionalannotation showed rs7194 may tag the effect of multiple amino acid residues andthe expression of HLA-DQB1 and HLA-DRB1; while rs4997052 showed the effect ofamino acid changes of HLA-B at position 116 as well as the expression of HLA-Band CCHCR1, which coexpressed with genes enriched in pathways ofspermatogenesis and male gamete generation. The novel variant rs4997052identified in our study can explain another approximately 0.66% of thephenotypic variances of NOA.
Conclusion(s): Wefine-mapped the MHC region and identified two loci that independently drove NOAsusceptibility. These results provide a deeper understanding of the associationmechanisms of MHC and NOA risk.
Keywords: Finemapping; GWAS; MHC; nonobstructive azoospermia.
引用本文：
Huang M, Zhu M, Jiang T, Wang Y, Wang C, Jin G, Guo X, Sha J, Dai J, Wang X, Hu Z. Fine mapping the MHC region identified rs4997052 as a new variant associated with nonobstructive azoospermia in Han Chinese males. Fertil Steril. 2019 Jan;111(1):61-68. doi: 10.1016/j.fertnstert.2018.08.052. Epub 2018 Nov 28. PMID: 30502936.
