可溶性晚期糖基化终末产物受体及其基因多态性与2型糖尿病的易感性分析

doi:10.6040/j.issn.1671-7554.0.2015.901

摘要/Abstract

摘要： 目的探讨可溶性晚期糖基化终末产物受体(sRAGE)水平及晚期糖基化终末产物受体(RAGE)基因单核苷酸位点多态性与2型糖尿病的关联。方法选择184例2型糖尿病患者作为糖尿病组,190例健康体检者作为正常对照组。ELISA方法检测sRAGE水平,PCR-TaqMan-MGB探针检测rs2070600、rs1800624、rs1800625及rs184003基因分型。结果糖尿病组sRAGE水平[M(P₂₅,P₇₅)]为1087.4(713.5,1213.4)pg/mL,正常对照组sRAGE为908.2(674.6,1107.1)pg/mL,两组差异有统计学意义(P<0.001)。糖尿病组与正常对照组间4个位点的最小等位基因频率分布均无统计学差异,且在基因型分析中也无阳性发现。线性相关分析表明,4个位点与sRAGE水平均无明显关联性。结论 sRAGE水平与2型糖尿病的发病相关,但RAGE位点多态性与糖尿病无明显关联。RAGE位点多态性与sRAGE水平无关联。

关键词: 可溶性晚期糖基化终末产物受体, 晚期糖基化终末产物受体, 单核苷酸基因多态, 2型糖尿病

Abstract: Objective To estimate the level of soluble receptor of advanced glycation end product (sRAGE) in type 2 diabetes mellitus, as well as its association with single nucleotide polymorphism (SNP) of receptor of advanced glycation end product (RAGE). Methods A total of 184 patients with type 2 diabetes mellitus and 190 healthy controls were recruited. ELISA was applied to test sRAGE, and PCR-TaqMan-MGB probe was used for the genotyping of rs2070600, rs1800624, rs1800625 and rs184003. Results The level of sRAGE[M(P₂₅,P₇₅)] in type 2 diabetes mellitus patients was[1087.4(713.5,1213.4) pg/mL], which was significantly higher than that of the controls[908.2(674.6,1107.1 pg/mL)]. As to the allele analysis, no significant differences were observed in the minor allele frequency comparisons of the 4 SNPs, and no association was found between the 4 SNPs and sRAGE level in the linear regression. Conclusion The elevated level of sRAGE is associated with type 2 diabetes mellitus, but the polymorphism of RAGE is not. There is no significant association between polymorphism of SNPs in RAGE and sRAGE level.

Key words: Single nucleotide polymorphism, Type 2 diabetes mellitus, Soluble receptor for advanced glycation end products, Receptor for advanced glycation end products

中图分类号:

R589

李方. 可溶性晚期糖基化终末产物受体及其基因多态性与2型糖尿病的易感性分析[J]. 山东大学学报（医学版）, 2015, 53(12): 57-61.

LI Fang. Association between receptor of advanced glycation end products gene polymorphisms, soluble receptor of advanced glycation end products and susceptibility of type 2 diabetes mellitus[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2015, 53(12): 57-61.

参考文献

[1] Xu Y, Wang L, He J, et al. Prevalence and control of diabetes in Chinese adults[J]. JAMA, 2013, 310(9):948-959.
[2] Maiese K, Morhan SD, Chong ZZ. Oxidative stress biology and cell injury during type 1 and type 2 diabetes mellitus[J]. Curr Neurovasc Res, 2007, 4(1):63-71.
[3] Santilli F, Vazzana N, Bucciarelli LG, et al. Soluble forms of RAGE in human diseases:clinical and therapeutical implications[J]. Curr Med Chem, 2009, 16(8):940-952.
[4] Niu W, Qi Y, Wu Z, et al. A meta-analysis of receptor for advanced glycation end products gene:four well-evaluated polymorphisms with diabetes mellitus[J]. Mol Cell Endocrinol, 2012, 358(1):9-17.
[5] Ng ZX, Kuppusamy UR, Iqbal T, et al. Receptor for advanced glycation end-product (RAGE) gene polymorphism 2245G/A is associated with pro-inflammatory, oxidative-glycation markers and sRAGE in diabetic retinopathy[J]. Gene, 2013, 521(2):227-233.
[6] Gaens KH, Ferreira I, van der Kallen CJ, et al. Association of polymorphism in the receptor for advanced glycation end products (RAGE) gene with circulating RAGE levels[J]. J Clin Endocrinol Metab, 2009, 94(12):5174-5180.
[7] Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1:diagnosis and classification of diabetes mellitus provisional report of a WHO consultation[J]. Diabet Med, 1998, 15(7):539-553.
[8] Schlueter C, Hauke S, Flohr AM, et al. Tissue-specific expression patterns of the RAGE receptor and its soluble forms-a result of regulated alternative splicing?[J]. Biochim Biophys Acta, 2003, 1630(1):1-6.
[9] Schmidt AM, Yan SD, Wautier JL, et al. Activation of receptor for advanced glycation end products:a mechanism for chronic vascular dysfunction in diabetic vasculopathy and atherosclerosis[J]. Circ Res, 1999, 84(5):489-497.
[10] Nakamura K, Yamagishi S, Adachi H, et al. Elevation of soluble form of receptor for advanced glycation end products (sRAGE) in diabetic subjects with coronary artery disease[J]. Diabetes Metab Res Rev, 2007, 23(5):368-371.
[11] Tan KC, Shiu SW, Chow WS, et al. Association between serum levels of soluble receptor for advanced glycation end products and circulating advanced glycation end products in type 2 diabetes[J]. Diabetologia, 2006, 49(11):2756-2762.
[12] Challier M, Jacqueminet S, Benabdesselam O, et al. Increased serum concentrations of soluble receptor for advanced glycation endproducts in patients with type 1 diabetes[J]. Clin Chem, 2005, 51(9):1749-1750.
[13] Yamagishi S, Matsui T, Nakamura K. Kinetics, role and therapeutic implications of endogenous soluble form of receptor for advanced glycation end products (sRAGE) in diabetes[J]. Curr Drug Targets, 2007, 8(10):1138-1143.
[14] Basta G, Sironi AM, Lazzerini G, et al. Circulating soluble receptor for advanced glycation end products is inversely associated with glycemic control and S100A12 protein[J]. J Clin Endocrinol Metab, 2006, 91(11):4628-4634.
[15] Thomas MC, Woodward M, Neal B, et al. The relationship between levels of advanced glycation end-products and their soluble receptor and adverse outcomes in adults with type 2 diabetes[J]. Diabetes Care, 2015[Epub ahead of print]. doi:10.2337/dc15-0925.
[16] Forbes JM, Soderlund J, Yap FY, et al. Receptor for advanced glycation end-products (RAGE) provides a link between genetic susceptibility and environmental factors in type 1 diabetes[J]. Diabetologia,2011, 54(5):1032-1042.
[17] Lu W, Feng B. The-374A allele of the RAGE gene as a potential protective factor for vascular complications in type 2 diabetes:a meta-analysis[J]. Tohoku J Exp Med, 2010, 220(4):291-297.
[18] 顾喆瑶,姚勇,谢田华,等. RAGE基因-429T>C多态性与无锡汉族人群糖尿病视网膜病变的相关性[J].中华眼视光学与视觉科学杂志, 2015, 17(2):81-85. GU Zheyao, YAO Yong, XIE Tianhua, et al. Correlation analysis of the-429T>C polymorphism of advanced glycation end products of the receptor gene and type 2 diabetic retinopathy in Han people in the Wuxi area[J]. Chinese Journal of Optometry Ophthalmology and Visual Science, 2015, 17(2):81-85.
[19] Haldar SR, Chakrabarty A, Chowdhury S, et al. Oxidative stress-related genes in type 2 diabetes:association analysis and their clinical impact[J]. Biochem Genet, 2015, 53(4-6):93-119.
[20] Kang P, Tian C, Jia C. Association of RAGE gene polymorphisms with type 2 diabetes mellitus, diabetic retinopathy and diabetic nephropathy[J]. Gene, 2012, 500(1):1-9.
[21] Bansal S, Chawla D, Banerjee BD, et al. Association of RAGE gene polymorphism with circulating AGEs level and paraoxonase activity in relation to macro-vascular complications in Indian type 2 diabetes mellitus patients[J]. Gene, 2013, 526(2):325-330.
[22] Wu TL, Tsai CC, Wang YY, et al. The association between the RAGE G82S polymorphism, sRAGE and chronic periodontitis in Taiwanese individuals with and without diabetes[J]. J Periodontal Res, 2015[Epub ahead of print] doi:10.1111/jre.12282.
[23] Jang Y, Kim JY, Kang SM, et al. Association of the Gly82Ser polymorphism in the receptor for advanced glycation end products (RAGE) gene with circulating levels of soluble RAGE and inflammatory markers in nondiabetic and nonobese Koreans[J]. Metabolism, 2007, 56(2):199-205.

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