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目的 探索Toll样受体4(Toll-like receptor 4,TLR4)基因多态性与2型糖尿病并发肺结核(type 2 diabetes mellitus complicated with pulmonary tuberculosis,T2DM-PTB)患者发生糖尿病性下肢血管病变(lower extremity arterial disease,LEAD)的关系.方法 选取2013年9月至2015年6月期间,在黑龙江省传染病防治院就诊的T2DM-PTB发生LEAD的患者87例(观察组)及T2DM-PTB未发生LEAD患者68例(对照组),所有患者于纳入研究时采集基本信息及血液样本.基因组DNA提取试剂盒提取血液DNA,采用实时荧光定量PCR技术(Taqman探针法)对TLR4基因的3个基因位点(rs7873784、rs1927911及rs1927914)进行基因多态性检测.结果 观察组和对照组的TLR4基因单核苷酸多态性(single nucleotide polymorphisms,SNPs)位点等位基因分布:rs7873784位点G等位基因两组分别为91.38％(159/174)、91.18％(124/136),C等位基因两组分别为8.62％(15/174)、8.82％(12/136),两组间差异无统计学意义(x2=0.00,P=0.950);rs1927911位点T等位基因两组分别为59.20％(103/174)、61.76％(84/136),C等位基因两组分别为40.80％(71/174)、38.24％(52/136),两组间差异无统计学意义(x2 =0.21,P=0.646);rs1927914位点T等位基因两组分别为59.77％(104/174)、64.71％(88/136),C等位基因两组分别为40.23％(70/174)、35.29％(48/136),两组间差异无统计学意义(x2=0.79,P=0.374).观察组和对照组的TLR4基因SNP位点基因型分布:rs7873784位点GG基因型两组分别为82.76％(72/87)、82.35 ％(56/68),GC基因型两组分别为17.24％(15/87)、17.65％(12/68),两组间差异无统计学意义(x2=0.00,P=0.947);rs1927911位点TT基因型两组分别为32.18％(28/87)、35.30％(24/68),CT基因型两组分别为54.02％(47/87)、52.94％(36/68),CC基因型两组分别为13.80％(12/87)、11.76％(8/68),两组间差异无统计学意义(x2 =0.24,P=0.887);rs1927914位点TT基因型两组分别为33.33％(29/87)、42.65％(29/68),CT基因型两组分别为52.87％(46/87)、44.12％(30/68),CC基因型两组分别为13.80％(12/87)、13.23％(9/68),两组间差异无统计学意义(x2=1.49,P=0.475).TLR4基因rs7873784位点:与野生纯合基因型GG相比,GC基因型的调整OR值为0.90(95％CI:0.39～2.06,P=0.80).rs1927911位点:与野生纯合基因型TT相比,CT基因型及CC基因型的调整OR值分别为1.00(95％CI:0.51～1.97,P=1.00)和1.29(95％CI:0.46～3.66,P=0.63);rs1927914位点:与野生纯合基因型TT相比,CT基因型及CC基因型的调整OR值分别为1.27(95％CI:0.64～2.51,P=0.49)和1.24(95％CI:0.47～3.27,P=0.67).3个基因位点各基因型间的差异均无统计学意义(P值均＞0.05).结论 TLR4基因rs7873784、rs1927911和rs1927914位点多态性与T2DMTB患者发生LEAD无关.“,”Objective To investigate the relationship between TLR4 gene polymorphism and LEAD in patients with T2DM-PTB.Methods We recruited 87 cases with T2DM-PTB patients complicated with LEAD and 68 cases with T2DM-PTB from Infectious Hospital of Heilongjiang Province between September 2013 and June 2015.The basic information of both T2DM-PTB patients complicated with LEAD and T2DM-PTB patients were collected.Meanwhile,peripheral blood was collected in order to undergo gene polymorphism analysis.DNA was extracted by genomic DNA extraction kits and genotyping was accomplished by using Real-time PCR (Taqman probe method).Three TLR4 gene loci (rs 7873784,rs1927911,rs1927914) were tested.Results Allele distribution of TLR4 gene SNPs locus in the observation group and the control group:The G allele of rs7873784 were 91.38％ (159/174) and 91.18％ (124/136) in the two groups,and the C allele were 8.62％ (15/174) and 8.82％ (12/136) in the two groups,respectively.There was no significant difference between the two groups (x2=0.00,P =0.950);The T allele of rs1927911 in two groups were 59.20％ (103/174) and 61.76％ (84/136),respectively,and the C allele were 40.80％ (71/174) and 38.24％ (52/136),respectively.There was no significant difference between the two groups (x2 =0.21,P=0.646);The T allele of rs1927914 in two groups were 59.77％ (104/174) and 64.71％ (88/136),respectively,and the C allele were 40.23％ (70/174) and 35.29％ (48/136),respectively.There was no significant difference between the two groups (x2 =0.79,P=0.374).Genotype distribution of TLR4gene SNP locus in the observation group and the control group:The GG genotypes of rs7873784 were 82.76％ (72/87) and 82.35％ (56/68) in two group,and the GC genotype of the two groups were 17.24％ (15/87) and 17.65％ (12/68),respectively.The difference between the two groups was not statistically significant (x2=0.00,P=0.947).The TT genotypes of rs1927911 were 32.18％ (28/87) and 35.30％ (24/68) in two groups,the CT genotype of the two groups were 54.02％ (47/87) and 52.94％ (36/68),and the CC genotype of the two groups were 13.80％ (12/87),11.76％ (8/68),respectively.The difference between the two groups was not statistically significant (x2 =0.24,P=0.887).The TT genotypes of rs1927914 were 33.33％ (29/87) and 42.65％ (29/68) in two groups,the CT genotypes of two groups were 52.87％ (46/87) and 44.12％ (30/68),and the CC genotypes of two groups were 13.80％ (12/87),13.23％ (9/68),respectively.The difference between the two groups was not statistically significant (x2 =1.49,P =0.475).Rs7873784 gene locus of TLR4:compared with wild homozygous genotype GG,the adjusted OR value of GC genotype was 0.90 (95％CI:0.39-2.06,P=0.80).Rs1927911 gene locus of TLR4:compared with wild homozygous genotype TT,the adjusted OR values of CT genotype and CC genotype were 1.00 (95％CI:0.51-1.97,P=1.00) and 1.29 (95％CI:0.46-3.66,P=0.63),respectively.Rs1927914 gene locus of TLR4:compared with wild homozygous genotype TT,the adjusted OR values of CT genotype and CC genotype were 1.27 (95％CI:0.64-2.51,P=0.49) and 1.24 (95％CI:0.47-3.27,P=0.67),respectively.There was no significant difference between the 3 genotypes at different loci (P ＞ 0.05).Conclusion The polymorphisms of rs7873784,rs1927911 and rs1927914 in TLR4 gene are not associated with LEAD in T2DM-PTB patients.