云南汉族人群CD40基因多态性与2型糖尿病的相关性
|
摘要
目的:研究CD40基因单核苷酸多态性(SNPs)位点rs1883832和rs4810485与云南汉人群2型糖尿病(T2DM)的相关性。方法:选取云南地区汉族人群T2DM患者343例作为病例组,健康体检者325例作为对照组,采用Taqman探针法对CD40基因SNPs位点rs1883832和rs4810485进行基因分型,分析其等位基因和基因型在病例组和对照组中的分布特征;构建2个SNPs位点的单倍型,分析各单倍型在2组中的分布差异。结果:rs4810485等位基因G在病例组中的分布频率显著高于对照组(P=0.014),该位点等位基因G可能是云南汉族人群T2DM发生的风险因素(OR=1.323、95%CI为1.057~1.655,P<0.05);rs1883832等位基因和基因型在两组中分布频率比较,差异无统计学意义(P>0.05);单倍型分析结果显示rs1883832C-rs4810485G单倍型可能会增加T2DM发生风险的因素(OR=1.43、95%CI为1.15~1.78,P<0.05)。结论:CD40基因SNPs位点rs4810485等位基因G和rs1883832C-rs4810485G单倍型可能是云南汉族人群T2DM发生的风险因素。
Objective: To investigate the association of single nucleotide polymorphisms( SNPs) in CD40 gene( rs1883832 and rs4810485) with type 2 diabetes mellitus( T2DM) in a Yunnan Han population. Methods: Taqman assay was used to genotype rs1883832 and rs4810485 in 343 T2DM patients and 325 healthy individuals. And the allelic and genotypic distribution of the SNPs in T2DM patients and healthy controls were analyzed. Additionally,the haplotypes were constructed and the association of the haplotypes with T2DM was analyzed. Results: The results showed that the allelic frequency of rs4810485 G was significantly higher in T2DM patients than healthy controls( P = 0. 014),and rs4810485 G may be a risk factor for T2DM in Yunnan Han population( OR = 1. 323,95% CI:1. 057 ~ 1. 655,P < 0. 05). However,there was no significant difference of the allelic and genotypic frequencies of rs1883832 between T2DM and control groups( P > 0. 05). In addition,the haplotype frequency of rs1883832 C-rs4810485 G was significantly higher in T2DM group( P < 0. 05,OR = 1. 43;95% CI: 1. 15 ~ 1. 78). Conclusion: Our results showed that the G allele of rs4810485 and the rs1883832 C-rs4810485 G haplotype might be associated with high risk of T2DM in a Yunnan Han population.
Objective: To investigate the association of single nucleotide polymorphisms( SNPs) in CD40 gene( rs1883832 and rs4810485) with type 2 diabetes mellitus( T2DM) in a Yunnan Han population. Methods: Taqman assay was used to genotype rs1883832 and rs4810485 in 343 T2DM patients and 325 healthy individuals. And the allelic and genotypic distribution of the SNPs in T2DM patients and healthy controls were analyzed. Additionally,the haplotypes were constructed and the association of the haplotypes with T2DM was analyzed. Results: The results showed that the allelic frequency of rs4810485 G was significantly higher in T2DM patients than healthy controls( P = 0. 014),and rs4810485 G may be a risk factor for T2DM in Yunnan Han population( OR = 1. 323,95% CI:1. 057 ~ 1. 655,P < 0. 05). However,there was no significant difference of the allelic and genotypic frequencies of rs1883832 between T2DM and control groups( P > 0. 05). In addition,the haplotype frequency of rs1883832 C-rs4810485 G was significantly higher in T2DM group( P < 0. 05,OR = 1. 43;95% CI: 1. 15 ~ 1. 78). Conclusion: Our results showed that the G allele of rs4810485 and the rs1883832 C-rs4810485 G haplotype might be associated with high risk of T2DM in a Yunnan Han population.
引文
[1]HU C,JIA W.Diabetes in China:Epidemiology and genetic risk factors and their clinical itility in personalized medication[J].2018,67(1):3-11.
[2]LI W,HUANG E.An update on type 2 diabetes mellitus as a risk factor for dementia[J].Journal of Alzheimer's disease:JAD,2016,53(2):393-402.
[3]CHAN J C N,MALIK V,JIA W,et al.Diabetes in Asia[J].Journal of the American Medical Association,2009,301(20):2129-2140.
[4]CHATZIGEORGIOU A,SEIJKENS T,ZARZYCKA B,et al.Blocking CD40-TRAF6 signaling is a therapeutic target in obesity-associated insulin resistance[J].Proceedings of the National Academy of Sciences of the United States of America,2014,111(7):2686-2691.
[5]UMEGAKI H.Type 2 diabetes as a risk factor for cognitive impairment:current insights[J].Clinical interventions in aging,2014,9(10):11-19.
[6]SHI Y Y,HE L.SHEsis,a powerful software platform for analyses of linkage disequilibrium,haplotype construction,and genetic association at polymorphism loci[J].Cell research,2005,15(2):97-98.
[7]YOON K H,LEE J H,KIM J W,et al.Epidemic obesity and type 2 diabetes in Asia[J].Lancet,2006,368(9548):1681-1688.
[8]ALMAWI W Y,NEMR R,KELESHIAN S H,et al.A replication study of 19 GWAS-validated type 2 diabetes at-risk variants in the Lebanese population[J].Diabetes Research and Clinical Practice,2013,102(2):117-122.
[9]CHANG Y C,LIU P H,YU Y H,et al.Validation of type 2 diabetes risk variants identified by genome-wide association studies in Han Chinese population:a replication study and meta-analysis[J].Plo S one,2014,9(4):e95045.
[10]PALMER N D,MCDONOUGH C W,HICKS P J,et al.A genome-wide association search for type 2 diabetes genes in African Americans[J].Plo S one,2012,7(1):e29202.
[11]CHEN X,HU Z,LI W,et al.Synergistic combined effect between CD40-1C>T and CTLA-4+6230G>A polymorphisms in Graves'disease[J].Gene,2015,567(2):154-158.
[12]ZHOU G,WANG Y,FANG Z,et al.CD40-1C>T polymorphism and the risk of lung cancer in a Chinese population[J].International Journal of Clinical and Experimental Pathology,2015,8(11):15163-15169.
[13]王小娜,张禹,王培智,等.云南汉族人群CD40基因多态性与肺癌发生发展的相关性[J].贵州医科大学学报,2017,42(4):383-388.
[14]CHEN J M,GUO J,WEI C D,et al.The association of CD40 polymorphisms with CD40 serum levels and risk of systemic lupus erythematosus[J].BMC genetics,2015,16(1):21.
[15]LEE Y H,BAE S C,CHOI S J,et al.Associations between the functional CD40 rs4810485 G/T polymorphism and susceptibility to rheumatoid arthritis and systemic lupus erythematosus:a meta-analysis[J].Lupus,2015,24(11):1177-1183.
[16]VAZGIOURAKIS V M,ZERVOU M I,CHOULAKI C,et al.A common SNP in the CD40 region is associated with systemic lupus erythematosus and correlates with altered CD40 expression:implications for the pathogenesis[J].Annals of the Rheumatic Diseases,2011,70(12):2184-2190.
[17]WANG M,LI Y,LI W,et al.The CD40 gene polymorphism rs1883832 is associated with risk of acute coronary syndrome in a Chinese case-control study[J].DNA and cell biology,2011,30(3):173-178.
[18]YUN Y,MA C,MA X.The SNP rs1883832 in CD40gene and risk of atherosclerosis in Chinese population:a meta-analysis[J].Plo S one,2014,9(5):e97289.
[2]LI W,HUANG E.An update on type 2 diabetes mellitus as a risk factor for dementia[J].Journal of Alzheimer's disease:JAD,2016,53(2):393-402.
[3]CHAN J C N,MALIK V,JIA W,et al.Diabetes in Asia[J].Journal of the American Medical Association,2009,301(20):2129-2140.
[4]CHATZIGEORGIOU A,SEIJKENS T,ZARZYCKA B,et al.Blocking CD40-TRAF6 signaling is a therapeutic target in obesity-associated insulin resistance[J].Proceedings of the National Academy of Sciences of the United States of America,2014,111(7):2686-2691.
[5]UMEGAKI H.Type 2 diabetes as a risk factor for cognitive impairment:current insights[J].Clinical interventions in aging,2014,9(10):11-19.
[6]SHI Y Y,HE L.SHEsis,a powerful software platform for analyses of linkage disequilibrium,haplotype construction,and genetic association at polymorphism loci[J].Cell research,2005,15(2):97-98.
[7]YOON K H,LEE J H,KIM J W,et al.Epidemic obesity and type 2 diabetes in Asia[J].Lancet,2006,368(9548):1681-1688.
[8]ALMAWI W Y,NEMR R,KELESHIAN S H,et al.A replication study of 19 GWAS-validated type 2 diabetes at-risk variants in the Lebanese population[J].Diabetes Research and Clinical Practice,2013,102(2):117-122.
[9]CHANG Y C,LIU P H,YU Y H,et al.Validation of type 2 diabetes risk variants identified by genome-wide association studies in Han Chinese population:a replication study and meta-analysis[J].Plo S one,2014,9(4):e95045.
[10]PALMER N D,MCDONOUGH C W,HICKS P J,et al.A genome-wide association search for type 2 diabetes genes in African Americans[J].Plo S one,2012,7(1):e29202.
[11]CHEN X,HU Z,LI W,et al.Synergistic combined effect between CD40-1C>T and CTLA-4+6230G>A polymorphisms in Graves'disease[J].Gene,2015,567(2):154-158.
[12]ZHOU G,WANG Y,FANG Z,et al.CD40-1C>T polymorphism and the risk of lung cancer in a Chinese population[J].International Journal of Clinical and Experimental Pathology,2015,8(11):15163-15169.
[13]王小娜,张禹,王培智,等.云南汉族人群CD40基因多态性与肺癌发生发展的相关性[J].贵州医科大学学报,2017,42(4):383-388.
[14]CHEN J M,GUO J,WEI C D,et al.The association of CD40 polymorphisms with CD40 serum levels and risk of systemic lupus erythematosus[J].BMC genetics,2015,16(1):21.
[15]LEE Y H,BAE S C,CHOI S J,et al.Associations between the functional CD40 rs4810485 G/T polymorphism and susceptibility to rheumatoid arthritis and systemic lupus erythematosus:a meta-analysis[J].Lupus,2015,24(11):1177-1183.
[16]VAZGIOURAKIS V M,ZERVOU M I,CHOULAKI C,et al.A common SNP in the CD40 region is associated with systemic lupus erythematosus and correlates with altered CD40 expression:implications for the pathogenesis[J].Annals of the Rheumatic Diseases,2011,70(12):2184-2190.
[17]WANG M,LI Y,LI W,et al.The CD40 gene polymorphism rs1883832 is associated with risk of acute coronary syndrome in a Chinese case-control study[J].DNA and cell biology,2011,30(3):173-178.
[18]YUN Y,MA C,MA X.The SNP rs1883832 in CD40gene and risk of atherosclerosis in Chinese population:a meta-analysis[J].Plo S one,2014,9(5):e97289.