A genetic variant in the placenta-derived MHC class I chain-related gene A increases the risk of preterm birth in a Chinese population
- 274 Downloads
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.
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.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
- Achour Y, Kammoun A, Ben Hamad M, Mahfoudh N, Chaabane S, Marzouk S, Keskes L, Gaddour L, Bahloul Z, Maalej A (2014) Association study of MICA gene polymorphisms with rheumatoid arthritis susceptibility in south Tunisian population. Int J Immunogenet 41:486–492. doi: 10.1111/iji.12146 CrossRefPubMedGoogle Scholar
- Blencowe H, Cousens S, Oestergaard MZ, Chou D, Moller AB, Narwal R, Adler A, Vera Garcia C, Rohde S, Say L, Lawn JE (2012) National, regional, and worldwide estimates of preterm birth rates in the year 2010 with time trends since 1990 for selected countries: a systematic analysis and implications. Lancet 379:2162–2172. doi: 10.1016/S0140-6736(12)60820-4 CrossRefPubMedGoogle Scholar
- Fest S, Brachwitz N, Schumacher A, Zenclussen ML, Khan F, Wafula PO, Casalis PA, Fill S, Costa SD, Mor G, Volk HD, Lode HN, Zenclussen AC (2008) Supporting the hypothesis of pregnancy as a tumor: survivin is upregulated in normal pregnant mice and participates in human trophoblast proliferation. Am J Reprod Immunol 59:75–83. doi: 10.1111/j.1600-0897.2007.00557.x CrossRefPubMedGoogle Scholar
- Gabriel SB, Schaffner SF, Nguyen H, Moore JM, Roy J, Blumenstiel B, Higgins J, DeFelice M, Lochner A, Faggart M, Liu-Cordero SN, Rotimi C, Adeyemo A, Cooper R, Ward R, Lander ES, Daly MJ, Altshuler D (2002) The structure of haplotype blocks in the human genome. Science 296:2225–2229. doi: 10.1126/science.1069424 CrossRefPubMedGoogle Scholar
- Hedlund M, Stenqvist AC, Nagaeva O, Kjellberg L, Wulff M, Baranov V, Mincheva-Nilsson L (2009) Human placenta expresses and secretes NKG2D ligands via exosomes that down-modulate the cognate receptor expression: evidence for immunosuppressive function. J Immunol 183:340–351. doi: 10.4049/jimmunol.0803477 CrossRefPubMedGoogle Scholar
- Kim J, Stirling KJ, Cooper ME, Ascoli M, Momany AM, McDonald EL, Ryckman KK, Rhea L, Schaa KL, Cosentino V, Gadow E, Saleme C, Shi M, Hallman M, Plunkett J, Teramo KA, Muglia LJ, Feenstra B, Geller F, Boyd HA, Melbye M, Marazita ML, Dagle JM, Murray JC (2013a) Sequence variants in oxytocin pathway genes and preterm birth: a candidate gene association study. BMC Med Genet 14:77. doi: 10.1186/1471-2350-14-77 CrossRefPubMedPubMedCentralGoogle Scholar
- Lo PH, Urabe Y, Kumar V, Tanikawa C, Koike K, Kato N, Miki D, Chayama K, Kubo M, Nakamura Y, Matsuda K (2013) Identification of a functional variant in the MICA promoter which regulates MICA expression and increases HCV-related hepatocellular carcinoma risk. PLoS One 8:e61279. doi: 10.1371/journal.pone.0061279 CrossRefPubMedPubMedCentralGoogle Scholar
- Lu M, Xia B, Ge L, Li Y, Zhao J, Chen F, Zhou F, Zhang X, Tan J (2009) Role of major histocompatibility complex class I-related molecules A*A5.1 allele in ulcerative colitis in Chinese patients. Immunology 128:e230–e236. doi: 10.1111/j.1365-2567.2008.02953.x CrossRefPubMedPubMedCentralGoogle Scholar
- Morgan TK, Tolosa JE, Mele L, Wapner RJ, Spong CY, Sorokin Y, Dudley DJ, Peaceman AM, Mercer BM, Thorp JM, O’Sullivan MJ, Ramin SM, Rouse DJ, Sibai B, Eunice Kennedy Shriver National Institute of Child H, Human Development Maternal-Fetal Medicine Units N (2013) Placental villous hypermaturation is associated with idiopathic preterm birth. J Matern Fetal Neonatal Med 26:647–653. doi: 10.3109/14767058.2012.746297 CrossRefPubMedGoogle Scholar
- Mortality GBD, Causes of Death C (2016) Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet 388:1459–1544. doi: 10.1016/S0140-6736(16)31012-1 CrossRefGoogle Scholar
- Mutsaerts MA, Groen H, Buiter-Van der Meer A, Sijtsma A, Sauer PJ, Land JA, Mol BW, Corpeleijn E, Hoek A (2014) Effects of paternal and maternal lifestyle factors on pregnancy complications and perinatal outcome. A population-based birth-cohort study: the GECKO Drenthe cohort. Hum Reprod 29:824–834. doi: 10.1093/humrep/deu006 CrossRefPubMedGoogle Scholar
- Padidela R, Bryan SM, Abu-Amero S, Hudson-Davies RE, Achermann JC, Moore GE, Hindmarsh PC (2012) The growth hormone receptor gene deleted for exon three (GHRd3) polymorphism is associated with birth and placental weight. Clin Endocrinol (Oxf) 76:236–240. doi: 10.1111/j.1365-2265.2011.04207.x CrossRefGoogle Scholar
- Rodriguez-Sanchez IP, Suarez-Caro S, Rivas-Solis F, Delgado-Enciso I, Sanchez-Chaparro MM, Gomez-Govea MA, Martinez-de-Villarreal LE, Valdez-Velazquez LL (2016) Association of the polymorphism 12109g>A from the REN gene as a risk factor for preterm birth. J Renin Angiotensin Aldosterone Syst 17:1470320316678159. doi: 10.1177/1470320316678159 PubMedGoogle Scholar
- Sheikh IA, Ahmad E, Jamal MS, Rehan M, Assidi M, Tayubi IA, AlBasri SF, Bajouh OS, Turki RF, Abuzenadah AM, Damanhouri GA, Beg MA, Al-Qahtani M (2016) Spontaneous preterm birth and single nucleotide gene polymorphisms: a recent update. BMC Genomics 17:759. doi: 10.1186/s12864-016-3089-0 CrossRefPubMedPubMedCentralGoogle Scholar
- Wang H, Parry S, Macones G, Sammel MD, Kuivaniemi H, Tromp G, Argyropoulos G, Halder I, Shriver MD, Romero R, Strauss JF 3rd (2006) A functional SNP in the promoter of the SERPINH1 gene increases risk of preterm premature rupture of membranes in African Americans. Proc Natl Acad Sci USA 103:13463–13467. doi: 10.1073/pnas.0603676103 CrossRefPubMedPubMedCentralGoogle Scholar
- Zhang H, Baldwin DA, Bukowski RK, Parry S, Xu Y, Song C, Andrews WW, Saade GR, Esplin MS, Sadovsky Y, Reddy UM, Ilekis J, Varner M, Biggio JR Jr, Eunice Kennedy Shriver National Institute of Child H, Human Development G, Proteomic Network for Preterm Birth R (2015) A genome-wide association study of early spontaneous preterm delivery. Genet Epidemiol 39:217–226. doi: 10.1002/gepi.21887 CrossRefPubMedPubMedCentralGoogle Scholar
- Zhou X, Wang J, Zou H, Ward MM, Weisman MH, Espitia MG, Xiao X, Petersdorf E, Mignot E, Martin J, Gensler LS, Scheet P, Reveille JD (2014) MICA, a gene contributing strong susceptibility to ankylosing spondylitis. Ann Rheum Dis 73:1552–1557. doi: 10.1136/annrheumdis-2013-203352 CrossRefPubMedGoogle Scholar