血小板活化因子乙酰水解酶基因多态性与早产儿颅内出血的关联性

张茜; 程欣茹; 徐淑玲; 时赞扬; 盛光耀

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中国当代儿科杂志 ›› 2012, Vol. 14 ›› Issue (08) : 612-615.

论著·临床研究

血小板活化因子乙酰水解酶基因多态性与早产儿颅内出血的关联性

张茜，程欣茹，徐淑玲，时赞扬，盛光耀

作者信息 +

Association between platelet-activating factor acetylhydrolase gene polymorphism and intracranial hemorrhage in preterm infants

ZHANG Qian, CHENG Xin-Ru, XU Shu-Ling, SHI Zan-Yang, SHENG Guang-Yao

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摘要

目的：本研究从基因水平探讨血小板活化因子乙酰水解酶（PAF-AH）基因第9外显子Val279Phe单核苷酸多态性与早产儿颅内出血是否具有关联性，为有效预防颅内出血的发生提供理论依据。方法：选取颅内出血早产儿58例作为出血组，无颅内出血早产儿65例作为对照组，应用聚合酶链式反应（PCR）检测PAF-AH第9外显子Val279Phe单核苷酸多态性位点的基因型及等位基因的分布情况，进行病例对照研究分析。结果：出血组和对照组PAF-AH第9外显子Val279Phe基因型分布频率差异有统计学意义（P＜0.05），其中出血组正常基因型频率（63.8%）明显低于对照组（81.5%）；出血组突变杂合子基因型（34.5%）明显高于对照组（16.9%）。两组PAF-AH等位基因分布频率差异亦有统计学意义（P＜0.05），其中出血组T 等位基因频率（19.0%）明显高于对照组（10.0%）。结论：PAF-AH第9外显子Val279Phe的单核苷酸基因多态性与早产儿颅内出血有关。

Abstract

OBJECTIVE: To explore whether Val279Phe single nucleotide polymorphisms (SNPs) in the 9th exon of platelet-activating factor acetylhydrolase (PAF-AH) are associated with intracranial hemorrhage in preterm infants. METHODS: A case-control study was performed. Polymerase chain reaction (PCR) was used to test genotype and allele frequencies of the 9th exon Val279Phe SNPs of PAF-AH in 58 preterm infants with intracranial hemorrhage (hemorrhage group) and 65 preterm infants without intracranial hemorrhage (control group). RESULTS: There were significant differences in genotype frequency of Val279Phe SNPs in the 9th exon of PAF-AH between the hemorrhage and control groups (P<0.05). Frequency of normal genotype in the hemorrhage group (63.8%) was significantly lower than in the control group (81.5%). In contrast, frequency of heterozygous genotype (34.5%) in the hemorrhage group was significantly higher than in control group (16.9%). There were also significant differences in allele frequency of Val279Phe SNPs in the 9th exon of PAF-AH between the two groups (P<0.05). T allele frequency in the hemorrhage group (19.0%) was significantly higher than in the control group (10.0%). CONCLUSIONS: Val279Phe SNPs in the 9th exon of PAF-AH may be associated with intracranial hemorrhage in preterm infants.

导出引用

张茜，程欣茹，徐淑玲，时赞扬，盛光耀. 血小板活化因子乙酰水解酶基因多态性与早产儿颅内出血的关联性[J]. 中国当代儿科杂志. 2012, 14(08): 612-615

ZHANG Qian, CHENG Xin-Ru, XU Shu-Ling, SHI Zan-Yang, SHENG Guang-Yao. Association between platelet-activating factor acetylhydrolase gene polymorphism and intracranial hemorrhage in preterm infants[J]. Chinese Journal of Contemporary Pediatrics. 2012, 14(08): 612-615

中图分类号： R722.6

参考文献

［1］Yoshida H, Imaizumi T, Fujimoto K, Itaya H, Hiramoto M, Yoshimizu N, et al. A mutation in plasmaplatelet-activating factor acetylhydrolase (Val279-Phe) is a genetic risk factor for cerebral hemorrhage but not for hypertension［J］.Thromb Haemost, 1998, 80(3): 372-375.

［2］Hiramoto M, Yoshida H, Imaizumi T, Yoshimizu N, Satoh K. A mutationin plasma platelet-activating factor acetylhydrolase (Val279-Phe) is a genetic risk factor for stroke［J］. Stroke, 1997, 28(12): 2417-2420.

［3］孙淑云，李江，张晨. 血小板活化因子乙酰水解酶基因突变（Val279-Phe）与急性脑出血的相关性研究［J］. 神经与精神卫生杂志，2003，3（2）：112-114.

［4］周丛乐. 颅内出血［M］//邵肖梅，叶鸿瑁，丘小汕.实用新生儿学. 第4版. 北京：人民卫生出版社，2011：706-715.

［5］Ito S, Noguchi E, Shibasaki M, Yamakawa-Kobayashi K, Watanabe H, Arinami T. Evidence for an association between plasma platelet-activating factor acetylhydrolase deficiency and increased risk of childhood atopic asthma［J］. J Hum Genet, 2002, 47(2): 99-101.

［6］Zhou X, He P. Temporal and spatial correlation of platelet-activating factor-induced increases in endothelial ［Ca2+］i, nitric oxide, and gap formation in intact venules［J］. Am J Physiol Heart Circ Physiol, 2011, 301(5): H1788-H1797.

［7］Yang Y, Yin J, Baumgartner W, Samapati R, Solymosi EA, Reppien E, et al. Platelet-activating factor reduces endothelial nitric oxide production: role of acid sphingomyelinase［J］. Eur Respir J, 2010, 36(2): 417-427.

［8］程欣茹.PAF及PAF-AH在早产儿颅内出血中的变化及其临床意义［D］.郑州大学，2012.

［9］Sekuri C, Cam FS, Tengiz I, Ercan E, Bayturan O, Berdeli A. Association of platelet-activating factor acetylhydrolase gene polymorphism with premature coronary artery disease in Turkish patients［J］. Anadolu Kardiyol Derg, 2006, 6(2): 132-134.

［10］Stafforini DM. Biology of platelet-activating factor acetylhydrolase (PAF-AH, lipoprotein associated phospholipase A2)［J］. Cardiovasc Drugs Ther, 2009, 23(1): 73-83.

［11］Stafforini DM, Satoh K, Atkinson DL, Tjoelker LW, Eberhardt C, Yoshida H, et al. Platelet-activating factor acetylhydrolase deficiency. A missensemutation near the active site of an anti-inflammatory phospholipase［J］. J Clin Invest, 1996, 97（12）: 2784-2791.

［12］Karabina SA, Gora S, Atout R, Ninio E. Extracellular phospholipases in atherosclerosis［J］. Biochimie, 2010, 92(6): 594-600.

［13］林大东，毕新岭，朱克军，缪明永，米庆胜，顾军.血小板活化因子乙酰水解酶基因Val279Phe突变与银屑病的相关性研究［J］. 中华皮肤科杂志，2005，38（3）：151-153.

［14］周春，经承学，李铭芳，谢湘芝. 血小板活化因子水解酶基因突变与原发性肾病综合征的相关性［J］. 实用儿科临床杂志，2007，22（23）：1814-1816.

［15］Stremler KE, Stafforini DM, Prescott SM, Zimmerman GA, McIntyre TM. An oxidized derivative of phosphatidylcholine is a substrate for the platelet-activating factor acetylhydrolase from human plasma［J］. J Biol Chem, 1989, 264(10): 5331-5334.

［16］Livnat I, Finkelshtein D, Ghosh I, Arai H, Reiner O. PAF-AH Catalytic Subunits Modulate the Wnt Pathway in Developing GABAergic Neurons［J］. Front Cell Neurosci, 2010, 4: 19.

［17］Glaw JT, Skalak TC, Peirce SM. Inhibition of canonical Wnt signaling increases microvascular hemorrhaging and venular remodeling in adult rats［J］. Microcirculation, 2010, 17(5): 348-357.