北京大学学报(医学版) ›› 2022, Vol. 54 ›› Issue (1): 18-22. doi: 10.19723/j.issn.1671-167X.2022.01.004

• 论著 • 上一篇    下一篇

细胞色素B-245α链及胆固醇酯转运蛋白基因多态性与广泛型侵袭性牙周炎易感性的关系

朱小玲1,李文静2,王宪娥2,宋文莉2,徐莉2,张立2,冯向辉2,路瑞芳2,释栋2,孟焕新2,()   

  1. 1.北京大学人民医院口腔科, 北京 100044
    2.北京大学口腔医学院·口腔医院牙周科,国家口腔医学中心,国家口腔疾病临床医学研究中心,口腔数字化医疗技术和材料国家工程实验室,口腔数字医学北京市重点实验室,北京 100081
  • 收稿日期:2021-10-18 出版日期:2022-02-18 发布日期:2022-02-21
  • 通讯作者: 孟焕新 E-mail:kqhxmeng@bjmu.edu.cn
  • 基金资助:
    国家自然科学基金(30471882);国家自然科学基金(30973319);国家自然科学基金(81271149)

Gene polymorphisms of cytochrome B-245 alpha chain (CYBA) and cholesteryl ester transfer protein (CETP) and susceptibility to generalized aggressive periodontitis

ZHU Xiao-ling1,LI Wen-jing2,WANG Xian-e2,SONG Wen-li2,XU Li2,ZHANG Li2,FENG Xiang-hui2,LU Rui-fang2,SHI Dong2,MENG Huan-xin2,()   

  1. 1. Department of Stomatology, Peking University People’s Hospital, Beijing 100044, China
    2. Department of Periodontology, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, Beijing 100081, China
  • Received:2021-10-18 Online:2022-02-18 Published:2022-02-21
  • Contact: Huan-xin MENG E-mail:kqhxmeng@bjmu.edu.cn
  • Supported by:
    National Natural Science Foundations of China(30471882);National Natural Science Foundations of China(30973319);National Natural Science Foundations of China(81271149)

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摘要:

目的: 探讨细胞色素B-245α链(cytochrome B-245 alpha chain,CYBA)rs4673及胆固醇酯转运蛋白(cholesteryl ester transfer protein,CETP)rs12720922基因多态性与广泛型侵袭性牙周炎(generalized aggressive periodontitis,GAgP)易感性的关系,为筛选GAgP的高危人群提供遗传学依据。方法: 采用病例对照研究方法,纳入GAgP患者372例和健康对照者133名。采用基于基质辅助的激光解吸电离飞行时间质谱技术进行CYBA rs4673及CETP rs12720922基因型测定,不同基因型与GAgP易感性的关系采用多重逻辑回归模型分析,对于两个基因多态性位点在GAgP易感性方面的交互作用采用似然比检验进行分析,交互作用模型采用相乘模型。结果: 372例GAgP患者平均年龄(27.5±5.2)岁,包括男性152例,女性220例;133名健康对照者平均年龄(28.8±7.1)岁,包括男性 53例,女性 80例;两组人群年龄差异有统计学意义(P<0.05),性别构成比差异无统计学意义(P>0.05)。CYBA rs4673位点CT/TT基因型频率在GAgP组显著高于对照组[18.0%(66/366) vs. 10.6%(14/132),P<0.05];调整年龄、性别后,与CC基因型个体相比,CT/TT基因型个体患GAgP风险明显增高(OR=1.86,95%CI:1.01~3.45,P<0.05)。CETP rs12720922位点基因型(GG、AA/AG)频率在GAgP组和对照组间差异无统计学意义(P>0.05)。CYBA rs4673和CETP rs12720922在GAgP易感性方面存在显著交互作用,与CYBA rs4673CC基因型及CETP rs12720922 AA/AG基因型个体相比,当两个位点分别为CT/TT基因型及GG基因型时,个体的GAgP患病风险显著增加(OR=3.25,95%CI:1.36~7.75,P<0.01)。结论: CYBA rs4673 CT/TT基因型与GAgP易感性相关,且与CETP rs12720922 GG基因型在GAgP易感性方面存在显著交互作用。

关键词: 侵袭性牙周炎, 细胞色素B-245a链, 胆固醇酯转运蛋白质类, 基因多态性, 交互作用

Abstract:

Objective: To explore the correlation of cytochrome B-245 alpha chain (CYBA) rs4673 and cholesteryl ester transfer protein (CETP) rs12720922 polymorphisms with the susceptibility of gene-ralized aggressive periodontitis (GAgP). Methods: The study was a case-control trial. A total of 372 GAgP patients and 133 periodontally healthy controls were recruited. The CYBA rs4673 and CETP rs12720922 polymorphisms were detected by matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS). Logistic regression models were used to analyze the correlation of CYBA rs4673 and CETP rs12720922 variants with the susceptibility of GAgP. The interaction between the two gene polymorphisms to the susceptibility of GAgP was analyzed by the likelihood ratio test. The interaction model adopted was the multiplication model. Results: The mean age of GAgP group and control group was (27.5±5.2) years and (28.8±7.1) years respectively. There was significant difference in age between the two groups (P<0.05). The gender distribution (male/female) was 152/220 and 53/80 respectively, and there was no significant difference between GAgP group and controls (P>0.05). For CYBA rs4673, the frequency of CT/TT genotype in the GAgP group was significantly higher than that in the controls [18.0% (66/366) vs. 10.6% (14/132), P<0.05]. After adjusting age and gender, the individuals with CT/TT genotype had a higher risk of GAgP (OR=1.86, 95%CI: 1.01-3.45, P<0.05), compared with CC genotype. There was no statistically significant difference in distributions of the CETP rs12720922 genotypes (GG, AA/AG) between GAgP patients and healthy controls (P>0.05). A significant interaction between CYBA rs4673 and CETP rs12720922 in the susceptibility to GAgP was observed. The GAgP risk of the individuals with CYBA rs4673 CT/TT and CETP rs12720922 GG genotypes was significantly increased (OR=3.25, 95%CI: 1.36-7.75, P<0.01), compared with those carrying CC and AA/AG genotypes. Conclusion: CYBA rs4673 CT/TT genotype is associated with GAgP susceptibility. There is a significant interaction between CYBA rs4673 CT/TT genotype and CETP rs12720922 GG genotype in the susceptibility of GAgP.

Key words: Aggressive periodontitis, Cytochrome B-245 alpha chain, Cholesterol ester transfer proteins, Gene polymorphism, Interaction

中图分类号: 

  • R781.42

表1

两组一般情况及基因型分布比较"

Characteristic Control (n=133) GAgP (n=372) P
Age/years, $\bar{x}\pm s$ 28.8±7.1 27.5±5.2 0.029
Gender, n(%) 0.839
Male 53 (39.8) 152 (40.9)
Female 80 (60.2) 220 (59.1)
PD/mm, $\bar{x}\pm s$ 1.76±0.46 4.85±1.06 <0.001
BI, $\bar{x}\pm s$ 1.09±0.31 3.50±0.53 <0.001
AL/mm, $\bar{x}\pm s$ 0.00±0.01 4.45±1.52 <0.001
CYBA rs4673, n(%) 0.046
CC 118 (89.4) 300 (82.0)
CT+TT 14 (10.6) 66 (18.0)
CETP rs12720922, n(%) 0.145
GG 99 (75.0) 298 (81.0)
AA+AG 33 (25.0) 70 (19.0)

表2

CYBA rs4673、CETP rs12720922基因与GAgP易感性的交互作用分析"

Genotype n OR (95%CI) P2
CC+AA/AG 88 Ref.
CT/TT+AA/AG 14 0.60 (0.19-1.90) 0.384
CC+GG 329 1.17 (0.70-1.96) 0.555
CT/TT+GG 66 3.25 (1.36-7.75) 0.008
P1 0.033
[1] Armitage GC, Cullinan MP. Comparison of the clinical features of chronic and aggressive periodontitis[J]. Periodontol 2000, 2010, 53(1):12-27.
doi: 10.1111/prd.2010.53.issue-1
[2] Inoue N, Kawashima S, Kanazawa K, et al. Polymorphism of the NADH/NADPH oxidase p22phox gene in patients with coronary artery disease[J]. Circulation, 1998, 97(2):135-137.
pmid: 9445163
[3] Fang S, Wang L, Jia C. Association of p22phox gene C242T polymorphism with coronary artery disease: A meta-analysis[J]. Thromb Res, 2010, 125(5):197-201.
[4] Tang RN, Wu P, An L. NADPH oxidase p22phox C242T polymorphism is associated with macroalbuminuria in diabetic patients: A meta-analysis[J]. J Diabetes Complications, 2017, 31(7):1207-1211.
[5] Snahnicanova Z, Mendelova A, Grendar M, et al. Association of polymorphisms in CYBA, SOD1, and CAT genes with type 1 diabetes and diabetic peripheral neuropathy in children and adolescents[J]. Genet Test Mol Biomarkers, 2018, 22(7):413-419.
doi: 10.1089/gtmb.2018.0018
[6] Nibali L, Parkar M, Brett P, et al. NADPH oxidase (CYBA) and FcgammaR polymorphisms as risk factors for aggressive periodontitis: A case-control association study[J]. J Clin Periodontol, 2006, 33(8):529-539.
pmid: 16899095
[7] Nibali L, O’Dea M, Bouma G, et al. Genetic variants associated with neutrophil function in aggressive periodontitis and healthy controls[J]. J Periodontol, 2010, 81(4):527-534.
doi: 10.1902/jop.2010.090543 pmid: 20367096
[8] Tall AR. Plasma cholesteryl ester transfer protein[J]. J Lipid Res, 1993, 34(8):1255-1274.
pmid: 8409761
[9] Westerterp M, van der Hoogt CC, de Haan W, et al. Cholesteryl ester transfer protein decreases high-density lipoprotein and severely aggravates atherosclerosis in APOE*3- Leiden mice[J]. Arterioscler Thromb Vasc Biol, 2006, 26(11):2552-2559.
pmid: 16946130
[10] Chapman MJ, Le Goff W, Guerin M, et al. Cholesteryl ester transfer protein: At the heart of the action of lipid-modulating therapy with statins, fibrates, niacin, and cholesteryl ester transfer protein inhibitors[J]. Eur Heart J, 2010, 31(2):149-164.
doi: 10.1093/eurheartj/ehp399 pmid: 19825813
[11] Wang J, Wang LJ, Zhong Y, et al. CETP gene polymorphisms and risk of coronary atherosclerosis in a Chinese population[J]. Lipids Health Dis, 2013(12):176.
[12] Blauw LL, Li-Gao R, Noordam R, et al. CETP (cholesteryl ester transfer protein) concentration: A genome-wide association study followed by mendelian randomization on coronary artery disease[J]. Circ Genom Precis Med, 2018, 11(5):e002034.
[13] Shimo-Nakanishi Y, Hasebe T, Suzuki A, et al. Functional effects of NAD(P)H oxidase p22(phox) C242T mutation in human leukocytes and association with thrombotic cerebral infarction[J]. Atherosclerosis, 2004, 175(1):109-115.
pmid: 15186954
[14] Wyche KE, Wang SS, Griendling KK, et al. C242T CYBA polymorphism of the NADPH oxidase is associated with reduced respi-ratory burst in human neutrophils[J]. Hypertension, 2004, 43(6):1246-1251.
doi: 10.1161/01.HYP.0000126579.50711.62
[15] Deguchi S, Hori T, Creamer H, et al. Neutrophil-mediated damage to human periodontal ligament-derived fibroblasts: role of lipopolysaccharide[J]. J Periodontal Res, 1990, 25(5), 293-299.
pmid: 2145414
[16] Altman LC, Baker C, Fleckman P, et al. Neutrophil-mediated damage to human gingival epithelial-cells[J]. J Periodontal Res, 1992, 27(1):70-79.
pmid: 1311041
[17] Leino L, Hurttia HM, Sorvajärvi K, et al. Increased respiratory burst activity is associated with normal expression of IgG-Fc-receptors and complement receptors in peripheral neutrophils from patients with juvenile periodontitis[J]. J Periodontal Res, 1994, 29(3):179-184.
pmid: 8207628
[18] Gronert K, Kantarci A, Levy BD, et al. A molecular defect in intracellular lipid signaling in human neutrophils in localized aggressive periodontal tissue damage[J]. J Immunol, 2004, 172(3):1856-1861.
doi: 10.4049/jimmunol.172.3.1856
[19] Blauw LL, Noordam R, Soidinsalo S, et al. Mendelian randomization reveals unexpected effects of CETP on the lipoprotein profile[J]. Eur J Hum Genet, 2019, 27(3):422-431.
doi: 10.1038/s41431-018-0301-5
[20] Bordoni L, Samulak JJ, Sawicka AK, et al. Trimethylamine N-oxide and the reverse cholesterol transport in cardiovascular disease: A cross-sectional study[J]. Sci Rep, 2020, 10(1):18675.
doi: 10.1038/s41598-020-75633-1 pmid: 33122777
[21] Fentoğlu O, Oz G, Tağdelen P, et al. Periodontal status in subjects with hyperlipidemia[J]. J Periodontol, 2009, 80(2):267-273.
doi: 10.1902/jop.2009.080104 pmid: 19186967
[22] Awartani F, Atassi F. Evaluation of periodontal status in subjects with hyperlipidemia[J]. J Contemp Dent Pract, 2010, 11(2):33-40.
pmid: 20228985
[23] Nepomuceno R, Pigossi SC, Finoti LS, et al. Serum lipid levels in patients with periodontal disease: A meta-analysis and meta-regression[J]. J Clin Periodontol, 2017, 44(12):1192-1207.
doi: 10.1111/jcpe.12792 pmid: 28782128
[24] Chu X, Newman J, Park B, et al. In vitro alteration of macrophage phenotype and function by serum lipids[J]. Cell Tissue Res, 1999, 296(2):331-337.
pmid: 10382275
[25] Croft KD, Beilin LJ, Vandongen R, et al. Leukocyte and platelet function and eicosanoid production in subjects with hypercholeste-rolaemia[J]. Atherosclerosis, 1990, 83(2/3):101-109.
doi: 10.1016/0021-9150(90)90155-C
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