Association of Leptin and Leptin Receptor Gene Polymorphism with Coronary Slow Flow Phenomenon
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摘要:
目的 探索冠状动脉慢血流现象（CSFP）的危险因素，并探讨瘦素基因LEP rs7799039及瘦素受体基因LEPR rs1137100、LEPR rs1137101的基因多态性与CSFP的相关性。 方法 入选CSFP组54例，正常冠状动脉血流（NCF）组46例。测定空腹血糖（FBG）、空腹胰岛素水平（FINS）等指标，采用稳态模型抵抗指数（HOMA-IR）评估胰岛素抵抗情况。采用酶联免疫吸附试验（ELISA）测定各组患者的血清瘦素、瘦素受体浓度。应用SNaPShot技术分析两组患者之间LEP rs7799039、LEPR rs1137100、LEPR rs1137101位点基因及基因型分布频率，以探讨瘦素及瘦素受体基因多态性与CSFP是否存在相关性，并通过多因素Logistic回归分析，探讨CSFP的相关危险因素。 结果 （1）与NCF组比较，CSFP组男性居多，且存在较高的瘦素水平（P = 0.000）及胰岛素抵抗指数（P = 0.046）；（2）CSFP组的LAD（校正后）、LCX、RCA及平均TFC均高于NCF组（P < 0.05）；（3）在CSFP组和NCF组患者中，LEP rs7799039、LEPR rs1137100、LEPR rs1137101基因及基因型分布频率无明显统计学差异（P > 0.05）；（4）Logistic逐步回归分析显示LEP、HOMA-IR为影响CSFP的相关危险因素（P < 0.05）。 结论 （1）血清瘦素、胰岛素抵抗为CSFP发生发展的危险因素；（2）LEP rs7799039、LEPR rs1137100、LEPR rs1137101基因多态性与CSFP无显著相关性。 Abstract:Objectives To search the risk factors of coronary slow flow phenomenon （CSFP） and to investigate the relationship between the polymorphism of leptin gene -LEP rs7799039, leptin receptor gene- LEPR rs1137100, LEPR rs1137101 and CSFP. Methods Fifty-four CSFP cases and 46 NCF cases were selected. Fasting blood glucose （FBG） and fasting insulin level （FINS） were measured. Homeostasis model resistance index （HOMA-IR） was used to evaluate insulin resistance. The serum leptin and leptin receptor concentrations were measured by enzyme-linked immunosorbent assay （ELISA）. The distribution frequency of LEP rs7799039, LEPR rs1137100 and LEPR rs1137101 were analyzed by SNaPShot technique to explore whether there is correlation between leptin and leptin receptor gene polymorphism and CSFP, and to explore the risk factors of CSFP by multivariate logistic regression analysis. Results 1. Compared with NCF group, CSFP group had higher leptin level （P = 0.000） and insulin resistance index （P = 0.046）. 2. Mean TFC of LAD （corrected）, LCX and RCA in CSFP group were higher than those in NCF group. 3.There was no significant difference in the distribution frequencies of LEP rs7799039, LEPR rs1137100 and LEPR rs1137101 between CSFP group and NCF group. 4.Logistic stepwise regression analysis showed that LEP and HOMA-IR were related risk factors for CSFP. Conclusions 1. LEP and insulin resistance are the risk factors for the development of CSFP. 2. There is no correlation between leptin and leptin receptor gene polymorphism and CSFP. -
Key words:
- Leptin /
- Leptin gene /
- Leptin receptor gene /
- Gene polymorphism /
- Coronary slow flow phenomenon
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表 1 两组受试者临床指标比较 [
$\bar x \pm s$ /n（%）/M（P25，P75）]Table 1. Comparison of clinical indexes between the two groups [
$\bar x \pm s $ /n（%）/M（P25，P75）]组别 CSFP组（n = 54） NCF组（n = 46） t/χ2 P 男性 36（66.7） 21（45.7） 4.476 0.034* 年龄（岁） 59.93 ± 10.70 60.13 ± 9.64 −0.100 0.921 吸烟史 27（50.0） 16（34.8） 2.347 0.126 高血压病史 34（63.0） 33（71.7） 0.865 0.352 糖尿病史 10（18.5） 7（15.2） 0.192 0.661 BMI（kg/m2） 24.83 ± 3.40 24.24 ± 3.23 0.870 0.386 TC（mmol/L） 4.46 ± 0.82 4.33 ± 1.17 0.633 0.529 TG（mmol/L） 1.75（0.69～6.02） 1.59（0.51～5.43） −1.477 0.140 HDL-C（mmol/L） 1.19 ± 0.27 1.23 ± 0.24 −0.780 0.437 LDL-C（mmol/L） 2.75 ± 0.64 2.65 ± 0.93 0.639 0.525 PLT（×109/L） 212.37 ± 53.05 221.41 ± 50.48 −0.869 0.387 MPV（fL） 10.92 ± 1.13 11.03 ± 1.22 −0.457 0.649 FBG（mmol/L） 5.28（3.42～11.10） 5.10（4.12～10.69） −0.858 0.391 FINS（uIU/mL） 19.60（4.33～210.09） 15.90（2.67～57.26） −1.646 0.100 HOMA-IR 4.53（0.66～56.02） 2.98（0.88～15.63） −1.667 0.046* LEP（ng/mL） 2.59（0.54～12.21） 1.00（0.56～11.51） −3.614 < 0.001 LEPR（ng/mL） 3.05（1.29～27.29） 2.78（0.95～26.42） −1.069 0.285 注：*P < 0.05。 
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表 2 两组受试者TIMI帧数比较 [M（P25，P75）]
Table 2. Comparison of TFC between the two groups [M（P25，P75）]
项目 CSFP组（n = 54） NCF组（n = 46） Z P LAD（校正后）-TFC 38.31（37.47，40.78） 31.01（29.67，33.18） −2.323 0.020* LCX-TFC 26.67（24.83，28.39） 19.31（17.20，20.98） −2.309 0.021* RCA-TFC 26.11（23.89，27.66） 19.10（15.23，21.24） −2.337 0.019* Mean TFC 30.52（29.65，31.27） 22.95（21.53，24.67） −2.627 0.009# 注：*P < 0.05, #P < 0.01。
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表 3 两组之间基因及基因型分布频率比较
Table 3. Comparison of gene and genotype distribution frequency between the two groups
基因型 CSFP组 NCF组 χ2 P Hardy-Weinberg检验（1） 频数 频率（%） 频数 频率（%） rs1137100 GG 37 68.5 32 69.6 0.721 0.739 0.89/0.82 GA 16 29.6 12 26.1 AA 1 1.9 2 4.3 G等位基因 90 83.3 76 82.6 0.018 0.892 A等位基因 18 16.7 16 17.4 rs1137101 GG 34 63.0 32 69.6 0.749 0.773 0.98/0.82 GA 18 33.3 12 26.1 AA 2 3.7 2 4.3 G等位基因 86 79.6 76 82.6 0.286 0.592 A等位基因 22 20.4 16 17.4 rs7799039 GG 2 3.7 2 4.3 2.173 0.343 0.68/0.99 GA 12 22.2 16 34.8 AA 40 74.1 28 60.9 G等位基因 16 14.8 20 21.7 1.614 0.204 A等位基因 92 85.2 72 78.3 注：（1）分别显示CSFP组/NCF组基因型Hardy-Weinberg平衡检测的P值。
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表 4 影响冠状动脉慢血流的二元Logistic回归分析
Table 4. Binary logistic regression analysis of coronary slow flow
变量 回归系数 标准误 Wald-χ2 P OR 95%CI HOMA-IR 0.092 0.048 3.595 0.038 1.096 1.005-1.205 LEP 0.241 0.110 4.800 0.028 1.273 1.026-1.579
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[1] Beltrame J F. Defining the coronary slow flow phenomenon[J]. Circulation Journal,2012,76(4):818-820. doi: 10.1253/circj.CJ-12-0205 [2] Sanghvi S,Mathur R,Baroopal A,et al. Clinical,demographic,risk factor and angiographic profile of coronary slow flow phenomenon:A single centre experience[J]. Indian Heart Journal,2018,70 (Suppl 3):S290-S294. [3] Cin V G,Pekdemir H,Camsar A,et al. Diffuse intimal thickening of coronary arteries in slow coronary flow[J]. Jpn Heart J,2003,44 (6):907-919. doi: 10.1536/jhj.44.907 [4] Gibson C M,Cannon C P,Daley W L,et al. TIMI frame count:a quantitative method of assessing coronary artery flow[J]. Circulation,1996,93(5):879-888. doi: 10.1161/01.CIR.93.5.879 [5] Mechanick J I,Zhao S,Garvey W T. Leptin,An Adipokine With Central Importance in the Global Obesity Problem[J]. Glob Heart,2018,13(2):113-127. doi: 10.1016/j.gheart.2017.10.003 [6] Bodary P F,Shen Y,Ohman M,et al. Leptin regulates neointima formation after arterial injury through mechanisms independent of blood pressure and the leptin receptor/STAT3 signaling pathways involved in energy balance[J]. Arterioscler Thromb Vasc Biol,2007,27(1):70-76. doi: 10.1161/01.ATV.0000252068.89775.ee [7] Katsiki N,Mikhailidis D P,Banach M. Leptin,cardiovascular diseases and type 2 diabetes mellitus[J]. Acta Pharmacol Sin,2018,39(7):1176-1188. doi: 10.1038/aps.2018.40 [8] de Faria A P,Ritter A M,Sabbatini A R,et al. Effects of leptin and leptin receptor SNPs on clinical- and metabolic-related traits in apparent treatment-resistant hypertension[J]. Blood Press,2017,26(2):74-80. doi: 10.1080/08037051.2016.1192945 [9] Matsuoka N,Ogawa Y,Hosoda K,et al. Human leptin receptor gene in obese Japanese subjects:evidence against either obesity-causing mutations or association of sequence variants with obesity[J]. Diabetologia,1997,40(10):1204-1210. doi: 10.1007/s001250050808 [10] Yang R,Barouch L A. Leptin signaling and obesity:Cardiovascular consequences[J]. Circulation Research,2007,101(6):545-559. doi: 10.1161/CIRCRESAHA.107.156596 [11] Nowzari Z,Masoumi M,Nazari-Robati M,et al. Association of polymorphisms of leptin,leptin receptor and apelin receptor genes with susceptibility to coronary artery disease and hypertension[J]. Life Sci,2018,207:166-171. doi: 10.1016/j.lfs.2018.06.007 [12] Hawkins B M,Stavrakis S,Rousan T A,et al. Coronary slow flow:Prevalence and clinical correlations[J]. Circ J,Circ J.,2012,76(4):936-942. doi: 10.1253/circj.CJ-11-0959 [13] Beltrame J F,Limaye S B,Horowitz J D. The coronary slow flow phenomenon:A new coronary microvascular disorder[J]. Cardiology,2002,97(4):197-202. doi: 10.1159/000063121 [14] Chen P, Baylin A, Lee J, et al. The association between sleep duration and sleep timing and insulin resistance among adolescents in Mexico City[J]. J Adolesc Health, 2020, 18: S1054-139X（20）30609-1. doi: 10.1016/j.jado health.2020.10.012. [15] X Cai,Y Su,G Shi,et al. GW26-e3963 Interleukin-10 promotor polymorphism and slow coronary flow[J]. J AM COLL CARDIOL,2015,66(16):C173-C173. [16] Khazaei M,Tahergorabi Z. Leptin and its cardiovascular effects:Focus on angiogenesis[J]. Adv Biomed Res,2015,4(1):79. doi: 10.4103/2277-9175.156526 [17] 朱小刚,高霏,申华,等. 冠状动脉慢血流385例患者的临床特征及随访结果[J]. 临床和实验医学杂志,2018,17(20):2179-2183. doi: 10.3969/j.issn.1671-4695.2018.20.015 [18] Rohde K,Keller M,la Cour Poulsen L,et al. Genetics and epigenetics in obesity[J]. Metabolism,2019,92:37-50. doi: 10.1016/j.metabol.2018.10.007 -
