Research Papers:

Mitochondrial DNA sequencing and large-scale genotyping identifies MT-ND4 gene mutation m.11696G>A associated with idiopathic oligoasthenospermia

Juan Ji, Miaofei Xu, Zhenyao Huang, Lei Li, Hongxiang Zheng, Shuping Yang, Shilin Li, Li Jin, Xiufeng Ling, Yankai Xia, Chuncheng Lu _ and Xinru Wang

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Oncotarget. 2017; 8:52975-52982. https://doi.org/10.18632/oncotarget.17675

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Juan Ji1,2,3,*, Miaofei Xu1,2,*, Zhenyao Huang1,2,*, Lei Li4, Hongxiang Zheng4, Shuping Yang4, Shilin Li4, Li Jin4, Xiufeng Ling1,3, Yankai Xia1,2, Chuncheng Lu1,2 and Xinru Wang1,2

1State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029, China

2Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, China

3Department of Children Health Care, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing 210029, China

4State Key Laboratory of Genetic Engineering and Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai 200433, China

*The first three authors have contributed equally to this study and they should be regarded as joint first authors.

Correspondence to:

Chuncheng Lu, email: chunchenglu@njmu.edu.cn

Xinru Wang, email: xrwang@njmu.edu.cn

Keywords: oligoasthenospermia, mitochondrial DNA, genetic variant, haplogroup

Received: November 09, 2016     Accepted: March 13, 2017     Published: May 08, 2017


Genetic variants of mitochondrial DNA (mtDNA) were implicated to be associated with male infertility. Our previous whole mitochondrial genome sequencing and association study has identified two susceptibility mtDNA variants for oligoasthenospermia in Han Chinese men. In this study, we tested promising associations in an extended validation using 670 idiopathic oligoasthenospermia cases and 793 healthy controls to identify additional risk variants. We found that the genetic variant of m.11696G>A showed significantly higher frequency in the case group than that in the control group (odds ratio (OR) 2.21, 95% CI 1.21-4.04) (P=7.90×10-3). To elucidate the exact role of the genetic variants in spermatogenesis, two main sperm parameters (sperm count and motility) were taken into account. We found that m.11696G>A was associated with low sperm motility, with the OR of 2.38 (95 % CI 1.27-4.46) (P =5.22×10-3). These results advance our understanding of the genetic susceptibility to oligoasthenospermia and more functional studies are needed to provide insights into its pathogenic mechanism.

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