Association between 14 bp Insertion/Deletion Polymorphism of HLA-G Gene and Preeclampsia: A Meta-Analysis_Chinese Journal of Evidence-Based Medicine

Authors：

SHEN Yanting ¹ ,  YU Hong ¹ , WANG Bei ²

1. Department of Gynecology and Obstetrics, Zhongda Hospital Affiliated to Southeast University, Nanjing 210009, China;2. Department of Epidemiology, School of Public Health, Southeast University, Nanjing 210009, China;

Corresponding author：

YU Hong, Email: yuhong650325@sina.com

Keywords：

Preeclampsia; HLA-G; Polymorphism; Systematic review; Meta-analysis; Case-control study

DOI：

10.7507/1672-2531.20130167

Video：

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Objective 　To systematically review the association between 14 bp insertion/ deletion polymorphism of HLA-G gene and preeclampsia (PE).
Methods 　We electronically searched in the following databases: PubMed, Web of Science, EMbase, CBM, CNKI, WanFang Data, and VIP to collect all the case-control trials on the association between 14 bp insertion/ deletion polymorphism of HLA-G gene and PE. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data and assessed the quality of the included studies. Then, meta-analysis was performed using RevMan 5.1 software.
Results 　Totally 10 studies were recruited. The results of meta-analysis showed that, the preeclampsia group was higher than the control group in the frequencies of HLA-G +14 bp haplotype in the fetus and fathers and the frequencies of HLA-G +14 bp/+14 bp genotype in fathers, but its frequencies of fetal HLA-G −14 bp haplotype was significantly lower. Their pooled OR and 95%CI were 1.42 (1.10 to 1.84), 1.54 (1.25 to 1.90), 2.00 (1.19 to 3.38), and 0.67 (0.54 to 0.82). Compared with the control group, in the preeclampsia group the frequencies of HLA-G +14 bp/+14 bp genotype in fetus were higher, while the frequencies of HLA-G −14 bp/−14 bp genotype were lower (OR=1.75, 95%CI 1.11 to 2.77; OR= 0.57, 95%CI 0.41 to 0.81). In the preeclampsia group, the frequencies of mother (+14 bp/−14 bp)/ fetal (+14 bp/+14 bp) were higher than the control group (OR= 3.77, 95%CI 1.40 to 10.11), while those of mother (−14 bp/−14 bp)/ fetal (−14 bp/−14 bp) and those of father (−14 bp/−14 bp)/fetal (−14 bp/−14 bp) were lower (OR=0.52, 95%IC 0.31 to 0.85; OR=0.33, 95%CI 0.15 to 0.75).
Conclusion 　Paternal and fetal 14 bp insertion/ deletion polymorphism of HLA-G gene might be associated with preeclampsia. And maternal-fetal genotype compatibility analysis might provide new clues for the pathogenesis research and clinical diagnosis of preeclampsia.

Citation： SHEN Yanting,YU Hong,WANG Bei. Association between 14 bp Insertion/Deletion Polymorphism of HLA-G Gene and Preeclampsia: A Meta-Analysis. Chinese Journal of Evidence-Based Medicine, 2013, 13(8): 955-962. doi: 10.7507/1672-2531.20130167 Copy

1.	Walker JJ. Preeclampsia. The Lancet, 2000, 356(9237): 1260-1265.
2.	Murphy DJ, Striate GM. Mortality and morbidity associated with early onset preeclampsia. Hypertens Pregnancy, 2000, 19(2): 221.
3.	李泽均, 刘兴会, 何国琳, 等. 重度子痫前期早产与自发性早产母儿结局的比较研究. 中国循证医学杂志, 2010, 10(9): 1016-1022.
4.	Hviid TV. HLA-G in human reproduction:Aspects of genetics, function and pregnancy complications. Hum Repmd Update, 2006, 12(3): 2.
5.	丰有吉, 主编. 妇产科学. 第七版. 北京: 人民卫生出版社, 2005: 74-84.
6.	Ownby RL, Crocco E, Acevedo A, et al. Depression and risk for Alzheimer disease: systematic review, meta-analysis, and metaregression analysis. Arch Gen Psychiatry, 2006, 63(5): 530-538.
7.	Zhang Z, Li Y, Zhang LL, et al. Association of 14 bp insertion/deletion polymorphism of the HLA-G gene in father with severe preeclampsia in Chinese. Tissue Antigens, 2012, 80(2): 158-164.
8.	Iversen AC, Nguyen OTD, Tømmerdal LF, et al. The HLA-G 14 bp gene polymorphism and decidual HLA-G14 bp gene expression in pre-eclamptic and normal pregnancies. Journal of Reproductive Immunology, 2008, 78(2): 158-165.
9.	Vianna P, Dalmaz CA, Veit TD, et al. Immunogenetics of pregnancy: Role of a 14-bp deletion in the maternal HLA-G gene in primiparous pre-eclamptic Brazilian women. Human Immunology, 2007, 68(8), 668-674.
10.	Lin A, Yan WH, Dai MZ, et al. Maternal human leukocyte antigen-G polymorphism is not associated with pre-eclampsia in a Chinese Han population. Tissue Antigens, 2008, 68(4): 311-316.
11.	Hylenius S, Andersen AMN, Melbye M, et al. Association between HLA-G genotype and risk of preeclampsia: a case±control study using family triads. Molecular Human Reproduction, 2004, 10(4): 237-246.
12.	Bermingham J, Jenkins D, McCarthy T, et al. Genetic analysis of insulin-like growth factor II and HLA-G in pre-eclampsia. Biochemical Society Transactions, 2000, 28(2): 215-219.
13.	Humphrey KE, Harrison GA, Cooper DW, et al. HLA-G deletion polymorphism and preeclampsia/ eclampsia. British Journal of Obstetrics and Gynaecology, 1995, 102(9): 707-710.
14.	张展, 李莹, 张琳琳, 等. 父源性 HLA-G基因14 bp缺失多态性与早发型重度子痫前期的相关性研究. 中国妇幼保健, 2012, 27(11): 1710-1713.
15.	李红, 张琳琳, 贾莉婷, 等. 母儿中HLA-G 14 bp插人／缺失多态性在早发型、晚发型重度子痫前期和正常妊娠中分布的差异.现代妇产科进展, 2011, 20(3): 203-206.
16.	张展, 王婧彦, 张琳琳, 等. 人类白细胞抗原G基因14 bp缺失多态性与重度子痫前期发病的关系. 中华妇产科杂志, 2010, 45(5): 348-352.
17.	Ahn H, Park J, Gilman-Sachs A, et al. Immunologic Characteristics of Preeclampsia, a Comprehensive Review. Am J Reprod Immunol, 2011, 65(4): 377-394.
18.	Servitje EL, Lopez NG, Olson DM. An immunological insight into the origins of preeclampsia. Hum Reprod Update, 2010, 16(5): 510-524.
19.	Uzan J, Carbonne M, Piconne O, et al. Pre-eclampsia: pathophysiology, diagnosis,and management. Vasc Health Risk Manag, 2011, 7: 467-474.
20.	Servitje EL, Lopez NG, Olson DM. An immunological insight into the origins of preeclampsia. Hum Reprod Update, 2010, 16(5): 510-524.
21.	Favier B, LeMaoult J, Lesport E, et al. ILT2/HLA-G interaction impairs NK-cell functions through the inhibition of the late but not the early events of the NK-cell activating synapse. Faseb J, 2010, 24(3): 689–699.

1. Walker JJ. Preeclampsia. The Lancet, 2000, 356(9237): 1260-1265.
2. Murphy DJ, Striate GM. Mortality and morbidity associated with early onset preeclampsia. Hypertens Pregnancy, 2000, 19(2): 221.
3. 李泽均, 刘兴会, 何国琳, 等. 重度子痫前期早产与自发性早产母儿结局的比较研究. 中国循证医学杂志, 2010, 10(9): 1016-1022.
4. Hviid TV. HLA-G in human reproduction:Aspects of genetics, function and pregnancy complications. Hum Repmd Update, 2006, 12(3): 2.
5. 丰有吉, 主编. 妇产科学. 第七版. 北京: 人民卫生出版社, 2005: 74-84.
6. Ownby RL, Crocco E, Acevedo A, et al. Depression and risk for Alzheimer disease: systematic review, meta-analysis, and metaregression analysis. Arch Gen Psychiatry, 2006, 63(5): 530-538.
7. Zhang Z, Li Y, Zhang LL, et al. Association of 14 bp insertion/deletion polymorphism of the HLA-G gene in father with severe preeclampsia in Chinese. Tissue Antigens, 2012, 80(2): 158-164.
8. Iversen AC, Nguyen OTD, Tømmerdal LF, et al. The HLA-G 14 bp gene polymorphism and decidual HLA-G14 bp gene expression in pre-eclamptic and normal pregnancies. Journal of Reproductive Immunology, 2008, 78(2): 158-165.
9. Vianna P, Dalmaz CA, Veit TD, et al. Immunogenetics of pregnancy: Role of a 14-bp deletion in the maternal HLA-G gene in primiparous pre-eclamptic Brazilian women. Human Immunology, 2007, 68(8), 668-674.
10. Lin A, Yan WH, Dai MZ, et al. Maternal human leukocyte antigen-G polymorphism is not associated with pre-eclampsia in a Chinese Han population. Tissue Antigens, 2008, 68(4): 311-316.
11. Hylenius S, Andersen AMN, Melbye M, et al. Association between HLA-G genotype and risk of preeclampsia: a case±control study using family triads. Molecular Human Reproduction, 2004, 10(4): 237-246.
12. Bermingham J, Jenkins D, McCarthy T, et al. Genetic analysis of insulin-like growth factor II and HLA-G in pre-eclampsia. Biochemical Society Transactions, 2000, 28(2): 215-219.
13. Humphrey KE, Harrison GA, Cooper DW, et al. HLA-G deletion polymorphism and preeclampsia/ eclampsia. British Journal of Obstetrics and Gynaecology, 1995, 102(9): 707-710.
14. 张展, 李莹, 张琳琳, 等. 父源性 HLA-G基因14 bp缺失多态性与早发型重度子痫前期的相关性研究. 中国妇幼保健, 2012, 27(11): 1710-1713.
15. 李红, 张琳琳, 贾莉婷, 等. 母儿中HLA-G 14 bp插人／缺失多态性在早发型、晚发型重度子痫前期和正常妊娠中分布的差异.现代妇产科进展, 2011, 20(3): 203-206.
16. 张展, 王婧彦, 张琳琳, 等. 人类白细胞抗原G基因14 bp缺失多态性与重度子痫前期发病的关系. 中华妇产科杂志, 2010, 45(5): 348-352.
17. Ahn H, Park J, Gilman-Sachs A, et al. Immunologic Characteristics of Preeclampsia, a Comprehensive Review. Am J Reprod Immunol, 2011, 65(4): 377-394.
18. Servitje EL, Lopez NG, Olson DM. An immunological insight into the origins of preeclampsia. Hum Reprod Update, 2010, 16(5): 510-524.
19. Uzan J, Carbonne M, Piconne O, et al. Pre-eclampsia: pathophysiology, diagnosis,and management. Vasc Health Risk Manag, 2011, 7: 467-474.
20. Servitje EL, Lopez NG, Olson DM. An immunological insight into the origins of preeclampsia. Hum Reprod Update, 2010, 16(5): 510-524.
21. Favier B, LeMaoult J, Lesport E, et al. ILT2/HLA-G interaction impairs NK-cell functions through the inhibition of the late but not the early events of the NK-cell activating synapse. Faseb J, 2010, 24(3): 689–699.

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Association between 14 bp Insertion/Deletion Polymorphism of HLA-G Gene and Preeclampsia: A Meta-Analysis

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