NKG2D基因多态性与云南汉族人群2型糖尿病的相关性
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摘要
目的:研究NKG2D基因中的多态性位点与云南汉族人群2型糖尿病(T2DM)的易感性的关系。方法:采用Taq Man基因分型的方法对343例T2DM患者和325例健康对照人群的NKG2D基因多态性位点(rs2255336和rs2617160)进行基因分型,分析NKG2D基因多态性位点的等位基因和基因型在T2DM组和对照组人群中的分布差异;构建2个多态性位点的单倍型,分析各单倍型在2组中的分布差异。结果:结果显示,rs2255336等位基因在2组被检者中的分布频率比较,差异无统计学意义(P>0.05),rs2617160等位基因在2组被检者的分布频率比较,差异有统计学意义(P=0.030),该位点等位基因A在对照组中的分布频率显著高于对照组,可能是云南汉族人群T2DM的保护性因素(OR=0.79;95%CI为0.64~0.98)。结论:NKG2D基因中的多态性位点rs2617160等位基因A可能是云南汉族人群T2DM的保护性因素。
Objective: To investigate the association of SNP( single nucleotide polymorphisms) in NKG2D gene with type 2 diabetes mellitus( T2DM) in Yunnan Han population. Methods: The polymorphisms of NKG2D( rs2255336 and rs2617160) were genotyped by using Taqman assay in 343 T2DM patients and 325 healthy people. The allelic and genotypic frequencies of the SNP in T2DM group and control group were analyzed. Additionally,the haplotypes of two polymorphisms were constructed and the association of the haplotypes with T2DM group and control group was analyzed.Results: The results showed that the allelic frequency of rs2617160 allele A was significantly higher in control group than T2DM groups( P = 0. 030,OR = 0. 79; 95% CI: 0. 64 ~ 0. 98) likely due to the protective factor of T2DM in Chinese Han population in Yunnan province. However there was no significant difference of the distribution for rs2255336 between T2DM and control group( P > 0. 05). Conclusion: Results indicated that the allele A of rs2617160 in NKG2D gene might be the protective factor of T2DM in Chinese Han population in Yunnan province.
Objective: To investigate the association of SNP( single nucleotide polymorphisms) in NKG2D gene with type 2 diabetes mellitus( T2DM) in Yunnan Han population. Methods: The polymorphisms of NKG2D( rs2255336 and rs2617160) were genotyped by using Taqman assay in 343 T2DM patients and 325 healthy people. The allelic and genotypic frequencies of the SNP in T2DM group and control group were analyzed. Additionally,the haplotypes of two polymorphisms were constructed and the association of the haplotypes with T2DM group and control group was analyzed.Results: The results showed that the allelic frequency of rs2617160 allele A was significantly higher in control group than T2DM groups( P = 0. 030,OR = 0. 79; 95% CI: 0. 64 ~ 0. 98) likely due to the protective factor of T2DM in Chinese Han population in Yunnan province. However there was no significant difference of the distribution for rs2255336 between T2DM and control group( P > 0. 05). Conclusion: Results indicated that the allele A of rs2617160 in NKG2D gene might be the protective factor of T2DM in Chinese Han population in Yunnan province.
引文
[1]PARK M H,FALCONER C,VINER R M,et al.The impact of childhood obesity on morbidity and mortality in adulthood:a systematic review[J].Obesity Reviews,2012,13(11):985-1000.
[2]HU C,JIA W.Diabetes in China:Epidemiology and genetic risk factors and their clinical utility in personalized medication[J].Diabetes,2018,67(1):3-11.
[3]KEANE K N,CRUZAT V F,CARLESSI R,et al.Molecular events linking oxidative stress and inflammation to insulin resistance and 52-cell dysfunction[J].Oxidative Medicine&Cellular Longevity,2015,2015(1):181643.
[4]NIKOLAJCZYK B S,JAGANNATHAN-BOGDAN M,SHIN H,et al.State of the union between metabolism and the immune system in type 2 diabetes[J].Genes&Immunity,2011,12(4):239-250.
[5]RYAN A,MURPHY M,GODSON C,et al.Diabetes mellitus and apoptosis:inflammatory cells[J].Apoptosis,2009,14(12):1435-1450.
[6]GUO H,XU B,GAO L,et al.High frequency of activated natural killer and natural killer T-cells in patients with new onset of type 2 diabetes mellitus[J].Experimental biology and medicine(Maywood,NJ),2012,237(5):556-562.
[7]TSUJIMURA T,MATSUO Y,KEYAKI T,et al.Correlations of sleep disturbance with the immune system in type2 diabetes mellitus[J].Diabetes Research&Clinical Practice,2009,85(3):286-292.
[8]TREMBATH A P,SHARMA N,RAJU S,et al.A Protective role for NKG2D–H60a interaction via homotypic t cell contact in nonobese diabetic autoimmune diabetes pathogenesis[J].Immunohorizons,2017,1(9):198-212.
[9]ASADI-SAGHANDI A,SHAMS A.Peginterferon Alfa-2a/Ribavirin treatment efficacy in chronic hepatitis C patients is related to natural killer group 2D gene rs1049174GC polymorphism[J].2016,27(4):369-374.
[10]MARIASELVAM C M,TAMOUZA R,KRISHNAMOORTHY R,et al.Association of NKG2D gene variants with susceptibility and severity of rheumatoid arthritis[J].Clinical and experimental immunology,2017,187(3):369-375.
[11]TANIGUCHI R,KOYANO S,SUZUTANI T,et al.A Thr72Ala polymorphism in the NKG2D gene is associated with early symptomatic congenital cytomegalovirus disease[J].Infection,2015,43(3):353-359.
[12]杨晓蕾,谭芳,马千里,等.云南汉族人群NKG2D基因多态性与非小细胞肺癌发生和发展的相关性[J].贵州医科大学学报,2017,42(5):508-512,527.
[13]杨晓蕾,戴书颖,王小娜,等.云南汉族人群NKG2D基因多态性与宫颈癌发生发展的相关性[J].贵州医科大学学报,2018,43(3):259-263,304.
[14]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.
[15]LI Z,ZHANG Z,HE Z,et al.A partition-ligation-combination-subdivision EM algorithm for haplotype inference with multiallelic markers:update of the SHEsis(http://analysis.bio-x.cn)[J].Cell research,2009,19(4):519-523.
[16]FEUERER M,HERRERO L,CIPOLLETTA D,et al.Lean,but not obese,fat is enriched for a unique population of regulatory T cells that affect metabolic parameters[J].Nature medicine,2009,15(8):930-939.
[17]GROSCHEL C,HUBSCHER D,NOLTE J,et al.Efficient killing of murine pluripotent stem cells by natural killer(NK)cells requires activation by cytokines and partly depends on the activating NK receptor NKG2D[J].Frontiers in immunology,2017,8(8):70.
[18]MA J,GUO X,WU X,et al.Association of NKG2D genetic polymorphism with susceptibility to chronic hepatitis B in a Han Chinese population[J].Journal of medical virology,2010,82(9):1501-1507.
[19]IWASZKO M,SWIERKOT J,KOLOSSA K,et al.Influence of NKG2D genetic variants on response to Anti-TNF Agents in patients with rheumatoid arthritis[J].Genes,2018,9(2):592-598
[20]PIOTROWSKI P,LIANERI M,OLESIN'SKA M,et al.Prevalence of the NKG2D Thr72Ala polymorphism in patients with systemic lupus erythematosus[J].Molecular biology reports,2012,39(2):1343-1347.
[21]KABALAK G,THOMAS R M,MARTIN J,et al.Association of an NKG2D gene variant with systemic lupus erythematosus in two populations[J].Human immunology,2010,71(1):74-78.
[2]HU C,JIA W.Diabetes in China:Epidemiology and genetic risk factors and their clinical utility in personalized medication[J].Diabetes,2018,67(1):3-11.
[3]KEANE K N,CRUZAT V F,CARLESSI R,et al.Molecular events linking oxidative stress and inflammation to insulin resistance and 52-cell dysfunction[J].Oxidative Medicine&Cellular Longevity,2015,2015(1):181643.
[4]NIKOLAJCZYK B S,JAGANNATHAN-BOGDAN M,SHIN H,et al.State of the union between metabolism and the immune system in type 2 diabetes[J].Genes&Immunity,2011,12(4):239-250.
[5]RYAN A,MURPHY M,GODSON C,et al.Diabetes mellitus and apoptosis:inflammatory cells[J].Apoptosis,2009,14(12):1435-1450.
[6]GUO H,XU B,GAO L,et al.High frequency of activated natural killer and natural killer T-cells in patients with new onset of type 2 diabetes mellitus[J].Experimental biology and medicine(Maywood,NJ),2012,237(5):556-562.
[7]TSUJIMURA T,MATSUO Y,KEYAKI T,et al.Correlations of sleep disturbance with the immune system in type2 diabetes mellitus[J].Diabetes Research&Clinical Practice,2009,85(3):286-292.
[8]TREMBATH A P,SHARMA N,RAJU S,et al.A Protective role for NKG2D–H60a interaction via homotypic t cell contact in nonobese diabetic autoimmune diabetes pathogenesis[J].Immunohorizons,2017,1(9):198-212.
[9]ASADI-SAGHANDI A,SHAMS A.Peginterferon Alfa-2a/Ribavirin treatment efficacy in chronic hepatitis C patients is related to natural killer group 2D gene rs1049174GC polymorphism[J].2016,27(4):369-374.
[10]MARIASELVAM C M,TAMOUZA R,KRISHNAMOORTHY R,et al.Association of NKG2D gene variants with susceptibility and severity of rheumatoid arthritis[J].Clinical and experimental immunology,2017,187(3):369-375.
[11]TANIGUCHI R,KOYANO S,SUZUTANI T,et al.A Thr72Ala polymorphism in the NKG2D gene is associated with early symptomatic congenital cytomegalovirus disease[J].Infection,2015,43(3):353-359.
[12]杨晓蕾,谭芳,马千里,等.云南汉族人群NKG2D基因多态性与非小细胞肺癌发生和发展的相关性[J].贵州医科大学学报,2017,42(5):508-512,527.
[13]杨晓蕾,戴书颖,王小娜,等.云南汉族人群NKG2D基因多态性与宫颈癌发生发展的相关性[J].贵州医科大学学报,2018,43(3):259-263,304.
[14]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.
[15]LI Z,ZHANG Z,HE Z,et al.A partition-ligation-combination-subdivision EM algorithm for haplotype inference with multiallelic markers:update of the SHEsis(http://analysis.bio-x.cn)[J].Cell research,2009,19(4):519-523.
[16]FEUERER M,HERRERO L,CIPOLLETTA D,et al.Lean,but not obese,fat is enriched for a unique population of regulatory T cells that affect metabolic parameters[J].Nature medicine,2009,15(8):930-939.
[17]GROSCHEL C,HUBSCHER D,NOLTE J,et al.Efficient killing of murine pluripotent stem cells by natural killer(NK)cells requires activation by cytokines and partly depends on the activating NK receptor NKG2D[J].Frontiers in immunology,2017,8(8):70.
[18]MA J,GUO X,WU X,et al.Association of NKG2D genetic polymorphism with susceptibility to chronic hepatitis B in a Han Chinese population[J].Journal of medical virology,2010,82(9):1501-1507.
[19]IWASZKO M,SWIERKOT J,KOLOSSA K,et al.Influence of NKG2D genetic variants on response to Anti-TNF Agents in patients with rheumatoid arthritis[J].Genes,2018,9(2):592-598
[20]PIOTROWSKI P,LIANERI M,OLESIN'SKA M,et al.Prevalence of the NKG2D Thr72Ala polymorphism in patients with systemic lupus erythematosus[J].Molecular biology reports,2012,39(2):1343-1347.
[21]KABALAK G,THOMAS R M,MARTIN J,et al.Association of an NKG2D gene variant with systemic lupus erythematosus in two populations[J].Human immunology,2010,71(1):74-78.