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A genetic variant in the placenta-derived MHC class I chain-related gene A increases the risk of preterm birth in a Chinese population

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Abstract

Preterm birth (PTB) is a predominant contributor to neonatal mortality and morbidity worldwide. However, the pathophysiology of PTB is not well-understood. We tested the hypothesis that single-nucleotide polymorphisms (SNPs) in the placenta-derived MHC class I chain-related gene A (MICA) could disrupt placental development and hence result in PTB. Nineteen selected SNPs in MICA were genotyped in a case–control study of 127 premature infants and 634 term controls in a Chinese Han population. We found that significantly increased PTB risk was associated with homozygosity for the A variant of rs2256318 (adjusted odds ratio = 6.97 and 95% confidence interval = 2.34–20.74 for A/A, compared with G/G genotype, P = 0.001). In addition, the A/A genotype of rs2256318 was associated with decreased placental weight of neonates (β = −25.331; P = 0.033). Furthermore, stratified analysis demonstrated that the A/A genotype of rs2256318 was associated with increased PTB risk in female group. In addition, we observed statistical interaction between the polymorphism rs2516448 and sex (P = 0.04). No significant differences in the distribution of haplotypes between cases and controls were detected. Our results indicate that the polymorphism of rs2256318 in MICA may contribute to the etiology of PTB through interfering with placental development. These findings need to be further validated in larger and multi-ethnic populations.

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Acknowledgements

Thank Dr. Julian Little for amending our manuscript. We acknowledge Shanghai birth cohort. This work was supported by the National Natural Science Foundation of China (NSFC) Grants (81401212), by Shanghai Youth Eastern Scholar (QD 2015006), and by Shanghai Pujiang Talent Project (15PJ1405500). Julian Little is holder of Canada Research Chair in Human Genome Epidemiology.

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  1. Junjiao Song and Jing Li contributed equally to this work.

Authors and Affiliations

  1. Ministry of Education and Shanghai Key Laboratory of Children’s Environmental Health, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai, 200092, China

    Junjiao Song, Han Liu, Yuexin Gan, Yongjun Zhang, Ying Tian, Weiye Wang, Jun Zhang & Dan Chen

  2. Laboratory of Biochemistry and Molecular Biology, School of Life Science, Yunnan University, Kunming, China

    Yang Sun & Min Yu

  3. Department of Neonatology, Shanghai Children’s Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Jing Li

  4. Department of Obstetrics, Obstetrics and Gynecology Hospital of Fudan University, 128 Shenyang Road, Yangpu, Shanghai, 200090, China

    Fei Luo & Haidong Cheng

  5. School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Ottawa, Canada

    Julian Little

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  1. Junjiao Song
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  2. Jing Li
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  3. Han Liu
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Correspondence to Haidong Cheng or Dan Chen.

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Song, J., Li, J., Liu, H. et al. A genetic variant in the placenta-derived MHC class I chain-related gene A increases the risk of preterm birth in a Chinese population. Hum Genet 136, 1375–1384 (2017). https://doi.org/10.1007/s00439-017-1834-3

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