Correlation Between Inflammation-related Gene Polymorphisms and Efficacy of Warfarin Therapy after Heart Valve Replacement Surgery_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

 MIYe-dong ¹ , QINJian-wei ²

1. The First Affiliated Hospital with Nanjing Medical University, Nanjing 210000, P. R. China;
2. Department of Cardiothoracic Surgery, Jiangyin Municipal People's Hospital, Jiangyin 214400 jiangsu, P. R. China;

Corresponding?author：

MIYe-dong, Email: meiyedong643@163.com

Keywords：

Cardiac valve replacement; Warfarin; Matrix metalloproteinase-2 (MMP2); GG genotype; GC genotype; Polymorphism; Inflammation

DOI：

10.7507/1007-4848.20160253

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To clarify the relationship between the G/C polymorphism of inflammatory gene matrix metalloproteinase-2 (MMP2) and warfarin therapy after cardiac valve replacement (CVR). Methods We finally identified 96 patients who received additional warfarin therapy after CVR as a trial group and 78 patients without the warfarin therapy as a control group. Gene sequencing techniques were adopted to determine single nucleotide polymorphism allele. We analyzed genotype and clinical features of the two groups and explored the relationship between the different MMP2 geno-types and warfarin therapy after CVR. Logistic regression was used to analyze the correlation between genotypes and risk factors after CVR and Kaplan-Meier survival curves were performed to analyze the survival time and efficacy of patients carrying MMP2 GC and GG genotypes. Results The distribution of MMP2 genotype in patients receiving warfarin therapy after surgery was different from that in patients without warfarin therapy. The results of multivariate logistic regression analysis showed that GC and GG genotypes were risk factors of complications of CVR. The proportion of GG genotype was higher in the patients with postoperative complications compared with those without. The survival time of patients carrying genotype MMP2 GG was shorter than those carrying GC genotype (P < 0.05), which reveals that the level of MMP2 GG genotype was associated with the prognosis. Conclusion G allele of MMP2 is a risk factor of complications following CVR. GG genotype is relevant to CVR and prognosis, which can be regarded as a risk factor post CVR.

Citation： MIYe-dong, QINJian-wei. Correlation Between Inflammation-related Gene Polymorphisms and Efficacy of Warfarin Therapy after Heart Valve Replacement Surgery. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2016, 23(11): 1077-1081. doi: 10.7507/1007-4848.20160253 Copy

1.	張海燕, 羅萬慰, 馬守梅, 等.細胞色素P450酶4F2基因多態性對華法林劑量影響的研究.藥學與臨床研究, 2010, 18(4): 338-340.
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4.	楊晶晶, 于鋒, 葛衛紅, 等.華法林個體化劑量調整模型的建立和應用.藥學與臨床研究, 2010, 18(3): 269-273.
5.	Singh O, Sandanaraj E, Subramanian K, et al. The influence of CYP4F2 rs2108622 (V433M) on warfarin dose requirement in Asian patients. Drug Metab Pharmacolinet, 2011, 26(2): 130-136.
6.	Kolek M, Brat R. Cardiac rhythm and atrial transport function after surgical ablation of atrial fibrillation using cryoenergy:predictors and effectiveness of the procedure. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub, 2010, 154(1): 55-68.
7.	Cen HJ, Zeng WT, Leng XY, et al. CYP4F2 rs2108622: a minor significant genetic factor of warfarin dose in Han Chinese patients with mechanical heart valve replacement. Br J Clin Pharmacol, 2010, 70(2): 234-240.
8.	王紅娟, 劉瑜, 楊潔, 等.藥物基因組學方程對中國患者低強度華法林抗凝治療劑量的預測效果分析.中華老年多器官疾病雜志, 2012, 11(8): 584-587.
9.	Huang SW, Xiang DK, Huang L, et al. Influence of GGCX genotype on warfarin dose requirements in Chinese patients. Thromb Res, 2011, 127(2): 131-134.
10.	王芳芳, 郭心靈, 李菲菲, 等.基于華法林藥物基因組學的臨床用藥模型建立.分子診斷與治療雜志, 2012, 4(2): 89-94.
11.	Carlquist JF, Home BD, Mower C, et al. An evaluation of nine genetic variants related to metabolism of action of warfarin as applied to stable dose prediction. Thromb Thrombolysis, 2010, 30(3): 358-364.
12.	王醫成. PXR和VKORCl基因多態性對華法林穩定劑量的影響.中南大學碩士論文, 2010.
13.	Munafo MR, Flint J. Meta-analysis of genetic association studies. Trends Genet, 2014, 20: 439-444.
14.	Bouki KP, Katsafados MG, Chatzopoulos DN, et al. Inflammatory markers and plaque morphology: Anoptical coherence tomography study. Int J Cardiol, 2012, 154(3): 287-292.

1. 張海燕, 羅萬慰, 馬守梅, 等.細胞色素P450酶4F2基因多態性對華法林劑量影響的研究.藥學與臨床研究, 2010, 18(4): 338-340.
2. Limdi NA, Wadelius M, Cavallari L, et al. Warfarin pharmacogene-tics: a single VKORCl polymorphism is predictive of dose across 3 racial groups. Blood, 2010, 115(18): 3827-3834.
3. Ozer N, Cam N, Tangurek B, et al. The impact of CYP2C9 and VKORCl genetic polymorphism and patient characteristics upon warfarin dose requirements in an adult Turkish population. Heart Vessels, 2010, 25(2): 155-162.
4. 楊晶晶, 于鋒, 葛衛紅, 等.華法林個體化劑量調整模型的建立和應用.藥學與臨床研究, 2010, 18(3): 269-273.
5. Singh O, Sandanaraj E, Subramanian K, et al. The influence of CYP4F2 rs2108622 (V433M) on warfarin dose requirement in Asian patients. Drug Metab Pharmacolinet, 2011, 26(2): 130-136.
6. Kolek M, Brat R. Cardiac rhythm and atrial transport function after surgical ablation of atrial fibrillation using cryoenergy:predictors and effectiveness of the procedure. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub, 2010, 154(1): 55-68.
7. Cen HJ, Zeng WT, Leng XY, et al. CYP4F2 rs2108622: a minor significant genetic factor of warfarin dose in Han Chinese patients with mechanical heart valve replacement. Br J Clin Pharmacol, 2010, 70(2): 234-240.
8. 王紅娟, 劉瑜, 楊潔, 等.藥物基因組學方程對中國患者低強度華法林抗凝治療劑量的預測效果分析.中華老年多器官疾病雜志, 2012, 11(8): 584-587.
9. Huang SW, Xiang DK, Huang L, et al. Influence of GGCX genotype on warfarin dose requirements in Chinese patients. Thromb Res, 2011, 127(2): 131-134.
10. 王芳芳, 郭心靈, 李菲菲, 等.基于華法林藥物基因組學的臨床用藥模型建立.分子診斷與治療雜志, 2012, 4(2): 89-94.
11. Carlquist JF, Home BD, Mower C, et al. An evaluation of nine genetic variants related to metabolism of action of warfarin as applied to stable dose prediction. Thromb Thrombolysis, 2010, 30(3): 358-364.
12. 王醫成. PXR和VKORCl基因多態性對華法林穩定劑量的影響.中南大學碩士論文, 2010.
13. Munafo MR, Flint J. Meta-analysis of genetic association studies. Trends Genet, 2014, 20: 439-444.
14. Bouki KP, Katsafados MG, Chatzopoulos DN, et al. Inflammatory markers and plaque morphology: Anoptical coherence tomography study. Int J Cardiol, 2012, 154(3): 287-292.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Correlation Between Inflammation-related Gene Polymorphisms and Efficacy of Warfarin Therapy after Heart Valve Replacement Surgery

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