Relationship between HLA-G polymorphism and susceptibility to recurrent miscarriage: A meta-analysis of non-family-based studies

Springer Science and Business Media LLC - Tập 31 - Trang 173-184 - 2013
Wei Fan1, Shangwei Li1, Zhongying Huang1, Qiong Chen2
1Center of Reproductive Medicine, The West China Second University Hospital, Sichuan University, Chengdu, People’s Republic of China
2Nursing Faculty of the West China Second University Hospital, Sichuan University, Chengdu, People’s Republic of China

Tóm tắt

The HLA-G 14-bp insertion/deletion polymorphism had been inconsistently associated with recurrent miscarriage (RM) risk. We examined the association by performing a meta-analysis. Eligible articles were searched in PubMed, EMBASE and CNKI without language limitation. We included all the articles about two or more miscarriages associated with HLA-G 14-bp polymorphism. The odds ratios (ORs) with 95 % confidence intervals (CIs) were used to assess the strength of associations. Statistical analyses were performed by the STATA10.0 software. 17 studies were included, representing 1786 cases and 1574 controls. The current meta-analysis showed that 14-bp polymorphism was not associated with RM risk in all genetic models and allele contrast(+14 bp vs. −14 bp: OR = 1.13; 95 % CI, 0.96,1.32; +14 bp/+14 bp vs. −14 bp/−14 bp: OR = 1.16, 95 % CI, 0.85, 1.59; +14 bp/−14 bp vs. −14 bp/−14 bp: OR = 1.21, 95 % CI, 0.92,1.58; dominant model: OR = 1.33; 95 % CI, 0.99,1.78; recessive model: OR = 1.06; 95 % CI, 0.79,1.43). Moreover, a significant heterogeneity was evident across studies. On the other hand, the subgroup analysis demonstrated that there was a significant association between HLA-G 14-bp polymorphism and patients with three or more miscarriages(+14 bp vs. −14 bp: OR = 1.27; 95 % CI, 1.04, 1.55; dominant model: OR = 1.52; 95 % CI, 1.16, 1.99; and model +14 bp/−14 bp versus −14 bp/−14 bp: OR = 1.51; 95 % CI, 1.15, 1.97;). Our comprehensive meta-analysis indicated that there was insufficient evidence to demonstrate a conclusive association between the HLA-G 14-bp insertion/deletion polymorphism and the risk of RM. But HLA-G 14-bp insertion/deletion polymorphic variation was associated with RM risk in patients with three or more miscarriages. Larger and well-designed studies may eventually provide a better, comprehensive understanding of the association between the HLA-G 14-bp insertion/deletion polymorphism and RM in the future.

Tài liệu tham khảo

Mishell Jr DR. Recurrent abortion. J Reprod Med. 1993;38:250–9. Royal College of Obstetricians and Gynaecologists. The investigation and treatment of couples with recurrent first-trimester and second-trimester miscarriage. In: Green-top Guideline No17. London: Royal College of Obstetricians and Gynaecologists; 2011. American Society for Reproductive Medicine. Evaluation and treatment of recurrent pregnancy loss: a committee opinion. Fertil Steril. 2012;98:1103–11. Jaslow CR, Carney JL, Kutteh WH. Diagnostic factors identified in 1020 women with two versus three or more recurrent pregnancy losses. Fertil Steril. 2010;93:1234–43. Stephenson M. Frequency of factors associated with habitual abortion in 197 couples. Fertil Steril. 1996;66:24–9. Ren AG, Wang J. Methylenetetrahydrofolate reductase C677T polymorphism and the risk of unexplained recurrent pregnancy loss: A meta-analysis. Fertil Steril. 2006;86:1716–22. Pandey MK, Rani R, Agrawal S. An update in recurrent spontaneous abortion. Arch Gynecol Obstet. 2005;272(2):95–108. Trowsdale J, Betz AG. Mother’s little helpers: mechanisms of maternal–fetal tolerance. Nat Immunol. 2006;7:241–6. Kovats S, Main EK, Librach C, Stubblebine M, Fisher SJ, DeMars R. A class I antigen HLA-G, expressed in human trophoblasts. Science. 1990;248:220–3. Goldman-Wohl DS, Ariel I, Greenfield C, Hochner-Celnikier D, Cross J, Fisher S, et al. Lack of human leukocyte antigen-G expression in extravillous trophoblasts is associated with pre-eclampsia. Mol Hum Reprod. 2000;6:88–95. Hunt JS, Morales PJ, Pace JL, Fazleabas AT, Langat DK. A commentary on gestational programming and functions of HLA-G in pregnancy. Placenta. 2007;21:S57–63. Jassem RM, Shani WS, Loisel DA, Sharief M, Billstrand C, Ober C. HLA-G polymorphisms and soluble HLA-G protein levels in women with recurrent pregnancy loss from Basrah province in Iraq. Hum Immunol. 2012;73:811–7. Vercammen MJ, Verloes A, Van de Velde H, Haentjens P. Accuracy of soluble human leukocyte antigen-G for predicting pregnancy among women undergoing infertility treatment: meta-analysis. Hum Reprod Update. 2008;14:209–18. Consiglio CR, Veit TD, Monticielo OA, Mucenic T, Xavier RM, Brenol JC, et al. Association of the HLA-G gene +3142C > G polymorphism with systemic lupus erythematosus. Tissue Antigens. 2011;77:540–5. Hviid TV, Rizzo R, Christiansen OB, Melchiorri L, Lindhard A, Baricordi OR. HLA-G and IL-10 in plasma in relation to HLA-G genotype and polymorphisms. Immunogenetics. 2004;56:135–41. Tan V, Randall G, Fan V, Camoretti-Mercado B, Brockman-Schneider R, Pan L, et al. Allele-specific targeting of microRNAs to HLA-G and risk of asthma. Am J Hum Genet. 2007;81:829–34. Yan WH, Lin V, Chen XJ, Dai MZ, Gan LH, Zhou MY, et al. Association of the maternal 14-bp insertion polymorphism in the HLA-G gene in women with recurrent spontaneous abortions. Tissue Antigens. 2006;68:521–3. Hviid TV, Christiansen OB. Linkage disequilibrium between human leukocyte antigen (HLA) class II and HLA-G - possible implications for human reproduction and autoimmune disease. Hum Immunol. 2005;66:688–99. Hiby SE, King A, Sharkey A, Loke YW. Molecular studies of trophoblast HLA-G: polymorphism, isoforms, imprinting and expression in preimplantation embryo. Tissue Antigens. 1999;53:1–13. Hviid TV, Hylenius S, Rorbye C, Nielsen LG. HLA-G allelic variants are associated with differences in the HLA-G mRNA isoform profile and HLA-G mRNA levels. Immunogenetics. 2003;55:63–79. Rousseau P, Le Discorde M, Mouillot G, Marcou C, Carosella ED, Moreau P. The 14 bp deletion-insertion polymorphism in the 3′ UT region of the HLA-G gene influences HLA-G mRNA stability. Hum Immunol. 2003;64:1005–10. Rizzo R, Hviid TV, Stignani M, Balboni A, Grappa MT, Melchiorri L, et al. The HLA-G genotype is associated with IL-10 levels in activated PBMCs. Immunogenetics. 2005;57:172–81. Wang X, Jiang W, Zhang D. Association of 14-bp insertion/deletion polymorphism of HLA-G gene with unexplained recurrent spontaneous abortion: a meta-analysis. Tissue Antigens. 2013;81:108–15. Gong M, Long J, Liu Q, Deng HC. Association of the ADIPOQ rs17360539 and rs266729 polymorphisms with type 2 diabetes: a meta-analysis. Mol Cell Endocrinol. 2010;325:78–83. Akhter A, Faridi RM, Das V, Pandey A, Naik S, Agrawal S. In vitro up-regulation of HLA-G using dexamethasone and hydrocortisone in first-trimester trophoblast cells of women experiencing recurrent miscarriage. Tissue Antigens. 2012;80:126–35. Kano T, Mori T, Furudono M, Ishikawa H, Watanabe H, Kikkawa E, et al. Human leukocyte antigen may predict outcome of primary recurrent spontaneous abortion treated with paternal lymphocyte alloimmunization therapy. Am J Reprod Immunol. 2007;58:383–7. Liu YD, Shao JC, Wang ZM, Jing YM, Hu DC. Relationship of polymorphism of HLA-G 14 bp and RSA in the Kunmin. China Healthc Front. 2008;3:4–5. Su MT, Lin SH, Chen YC. Genetic association studies of angiogenesis- and vasoconstriction-related genes in women with recurrent pregnancy loss: a systematic review and meta-analysis. Hum Reprod Update. 2011;17:803–12. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21:1539–58. Wenquan N, Yue Q, Pingjin G, Dingliang Z. Association between angiotensin converting enzyme G2350A polymorphism and hypertension risk: a meta-analysis. J Renin-Angiotensin-Aldosterone Syst. 2011;12:8–14. Wu XY, Lu JJ, Zhang JX, Li H. The Bonferroni Method for Multiple Comparisons. J Evidence-Based Med. 2006;6:361–3. 374. Xue SG, Yang JQ, Yao FJ, Xu LD, Fan LA. Study on the polymorphism of the 14 bp deletion of HLA-G allele in patients with recurrent spontaneous abortion of unknown origin and normal deliveries. Curr Immunol. 2006;26:318–21. Li CQ, Zhang X, Bao WG, Ling AF, Yan WH. Association of the maternal 14-bp insertion polymorphism in the HLA-G gene in women with recurrent spontaneous abortions. Zhejiang Pract Med. 2009;14:449–50. Hviid TV, Hylenius S, Lindhard A, Christiansen OB. Association between human leukocyte antigen-G genotype and success of in vitro fertilization and pregnancy outcome. Tissue Antigens. 2004;64:66–9. Hviid TV, Hylenius S, Hoegh AM, Kruse C, Christiansen OB. HLA-G polymorphisms in couples with recurrent spontaneous abortions. Tissue Antigens. 2002;60:122–32. Sosnina KO, Zastavna DV, Terpylyak OI. The role of HLA-G 14 base pairs insertion/deletion polymorphism in the genesis of human early reproductive losses. Tissue Antigens. 2012;80:83. Larsen MH, Dahl M, Pass MB, Hviid TV, Christiansen OB, Bzorek M, et al. The non-classical human leukocyte antigen (HLA)-G in human reproduction and complications of pregnancy. Tissue Antigens. 2010;75:543–4. Da Graca BM, Dos Santos SJ. Sarturi P; HLA-G 14 bp/del genotypes in Brazilian couples with recurrent spontaneous abortions. Tissue Antigens. 2009;74:91–2. Kolte AM, Steffensen R, Nielsen HS, Hviid TV, Christiansen OB. Study of the structure and impact of human leukocyte antigen (HLA)-G-A, HLA-G-B, and HLA-G-DRB1 haplotypes in families with recurrent miscarriage. Hum Immunol. 2010;71:482–8. Christiansen OB, Kolte AM, Dahl M, Larsen EC, Steffensen R, Nielsen HS, et al. Maternal homozygocity for a 14 base pair insertion in exon 8 of the HLA-G gene and carriage of HLA class II alleles restricting HY immunity predispose to unexplained secondary recurrent miscarriage and low birth weight in children born to these patients. Hum Immunol. 2012;73:699–705. Shankarkumar U, Shankarkumar A, Chedda Z, Ghosh K. Role of 14-bp deletion/insertion polymorphism in exon 8 of the HLA-G gene in recurrent spontaneous abortion patients. J Hum Reprod Sci. 2011;4:143–6. Vargas RG, Sarturi PR, Mattar SB, Bompeixe EP, Silva Jdos S, Pirri A, et al. Association of HLA-G alleles and 3′ UTR 14 bp haplotypes with recurrent miscarriage in Brazilian couples. Hum Immunol. 2011;72:479–85. Aruna M, Sirisha PV, Andal Bhaskar S, Tarakeswari S, Thangaraj K, Reddy BM. Role of 14-bp insertion/deletion polymorphism in HLA-G among Indian women with recurrent spontaneous abortions. Tissue Antigens. 2011;77:131–5. Berger DS, Hogge WA, Barmada MM, Ferrell RE. Comprehensive analysis of HLA-G: implications for recurrent spontaneous abortion. Reprod Sci. 2010;17:331–8. Zhu Y, Huo Z, Lai J, Li S, Jiao H, Dang J, et al. Case–control study of a HLA-G 14-bp insertion-deletion polymorphism in women with recurrent miscarriages. Scand J Immunol. 2010;71:52–4. Suryanarayana V, Rao L, Kanakavalli M, Padmalatha V, Raseswari T, Deenadayal M, et al. Association between novel HLA-G genotypes and risk of recurrent miscarriages: a case–control study in a South Indian population. Reprod Sci. 2008;15:817–24. Sipak-Szmigiel O, Cybulski C, Lubiński J, Ronin-Walknowska E. HLA-G polymorphism in a Polish population and reproductive failure. Tissue Antigens. 2008;71:67–71. Xue S, Yang J, Yao F, Xu L, Fan L. Recurrent spontaneous abortions patients have more −14 bp/+14 bp heterozygotes in the 3′UT region of the HLA-G gene in a Chinese Han population. Tissue Antigens. 2007;69:153–5. Tripathi P, Abbas A, Naik S, Agrawal S. Role of 14-bp deletion in the HLA-G gene in the maintenance of pregnancy. Tissue Antigens. 2004;64:706–10. Shao JC, Hu DC, Chen J, Liu YD, Wang ZM. Relationship of polymorphism of HLA-G 14 bp and the expression of HLA-G mRNA with unexplained recurrent spontaneous abortion. J Pract Obstet Gynecol. 2011;27:698–701. Zhao YM, ZhenG ML, Zhang GL, Zhang YL, Hua AL, He JM. Related study between Serum levels of sHLA-G, HLA-G14bp insertion/deletion polymorphism and recurrent spontaneous abortion. Shanxi Med J. 2009;38:390–1. Cecati M, Giannubilo SR, Emanuelli M, Tranquilli AL, Saccucci F. HLA-G and pregnancy adverse outcomes. Med Hypotheses. 2011;76:782–4. Rizzo R, Andersen AS, Lassen MR, Sorensen HC, Bergholt T, Larsen MH, et al. Soluble human leukocyte antigen-G isoforms in maternal plasma in early and late pregnancy. Am J Reprod Immunol. 2009;62:320–38. Hill JA, Anderson DJ. Immunological mechanisms in recurrent spontaneous abortion. Arch Immunol Ther Exp. 1990;38:111–9. Rai R, Regan L. Recurrent miscarriage. Lancet. 2006;368:601–11. Kruse C, Steffensen R, Varming K, Christianen OB. A study of HLA-DR and -DQ alleles in 588 patients and 562 controls confirms that HLA-DRB1*03 is associated with recurrent miscarriage. Hum Reprod. 2004;19:1215–21. Christiansen OB, Pedersen B, Rosgaard A, Husth M. (2002) A randomized, double-blind, placebo-controlled trial of intravenous immunoglobulin in the prevention of recurrent miscarriage: evidence for a therapeutic effect in women with secondary recurrent miscarriage. Hum Reprod. 2002;17:809–16. Adams KM, Nelson JL. Microchimerism: an investigative frontier in autoimmunity and transplantation. J Am Med Assoc. 2004;291:1127–31. Huppertz B, Kaufmann P, Kingdom J. Trophoblast turnover in health and disease. Fetal Matern Med Rev. 2002;13:103–18. Christiansen OB, Pedersen B, Nielsen HS, Nybo Andersen AM. Impact of the sex of first child on the prognosis in secondary recurrent miscarriage. Hum Reprod. 2004;19(12):2946–51. Bulletti C, Flamigni C, Giacomucci E. Reproductive failure due to spontaneous abortion and recurrent miscarriage. Hum Reprod Update. 1996;2:118–36. Sbracia M, Cozza G, Grasso JA, Mastrone M, Scarpellini F. Semen parameters and sperm morphology in men in unexplained recurrent spontaneous abortion, before and during a 3 year follow-up period. Hum Reprod. 1996;11:117–20.