Song Junjiao, Li Jing, Liu Han, Gan Yuexin, Sun Yang, Yu Min, Zhang Yongjun, Luo Fei, Tian Ying, Wang Weiye, Zhang Jun, Little Julian, Cheng Haidong, Chen Dan
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.
Department of Neonatology, Shanghai Children's Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Hum Genet. 2017 Oct;136(10):1375-1384. doi: 10.1007/s00439-017-1834-3. Epub 2017 Sep 1.
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.
早产是全球新生儿死亡和发病的主要原因。然而，早产的病理生理学尚未完全明确。我们检验了这样一个假设，即胎盘来源的主要组织相容性复合体I类链相关基因A（MICA）中的单核苷酸多态性（SNP）可能会破坏胎盘发育，从而导致早产。在一项针对中国汉族人群的病例对照研究中，对127名早产儿和634名足月儿对照进行了19个选定的MICA基因SNP的基因分型。我们发现，rs2256318的A变体纯合子与早产风险显著增加相关（与G/G基因型相比，A/A基因型的调整比值比=6.97，95%置信区间=2.34-20.74，P=0.001）。此外，rs2256318的A/A基因型与新生儿胎盘重量降低相关（β=-25.331；P=0.033）。此外，分层分析表明，rs2256318的A/A基因型与女性组早产风险增加相关。此外，我们观察到多态性rs2516448与性别之间存在统计学交互作用（P=0.04）。病例组和对照组之间单倍型分布没有显著差异。我们的结果表明，MICA中rs2256318的多态性可能通过干扰胎盘发育而导致早产。这些发现需要在更大规模和多民族人群中进一步验证。
