甘露糖结合凝集素基因与中国北方汉族人群2型糖尿病的关系

Association between mannose-binding-lectin gene and type 2 diabetic patients in Chinese population living in the northern areas of China

目的探讨甘露糖结合凝集素（MBL）基因与中国北方汉族人群2型糖尿病（T2DM）的关系。方法收集318例北方汉族T2DM患者和448名血糖正常健康对照，应用多重SNaPshot技术检测MBL2基因rs1800450、rs1800451和rs11003125位点多态性。logistic回归分析该基因变异和其他危险因素对T2DM的作用。Haploview软件对3个位点进行连锁不平衡分析和单倍型分析。结果rs1800451位点检测到的基因型均为CC，在病例和对照中均不存在变异，rs1800450和rs11003125位点多态性的分布符合Hardy-Weinberg平衡。rs1800450多态位点基因型频率和等位基因频率在病例组和对照组中分布的差异均有统计学意义（P=0．006和P=0．003），rs11003125多态位点基因型频率和等位基凶频率的差异也均有统计学意义（P=0．010和P=0．004）。多元logistic回归模型分析显示超重、中心性肥胖、高胆固醇血症是T2DM的危险因素。携带rs1800450位点GG基因型以及rs11003125位点（GC＋CC）基因型患T2DM危险显著增高。单倍型分析结果显示rs1800450和rs11003125单倍型构成为GC患糖尿病的风险明显增高（OR=2．21，95％CI：1．47～3．33，P=0．000）。结论MBL2基因第1外显子rs1800450多态、启动子rs11003125多态与T2DM可能相关。携带rs1800450位点G等位基因以及rs11003125位点C等位基因可能是汉族人群发生T2DM的危险因素。

Objective To investigate whether the mannose-binding-lectin 2 （MBL2） gene was associated with type 2 diabetes in the populations living the northern part of China. Methods The study involved 318 type 2 diabetic patients and 448 normoglycemic controls. The variances of rs 1800450, rs 1800451 and rs 11003125 were determined by the Multiplex SNaPshot method. Fasting blood-glucose, triglyceride and total cholesterol were also measured. All of these results were analyzed by logistic regression method. Linkage disequilibrium and Haplotype measures were computed in all samples using Haploview. Results There seemed no mutation on rs 1800451 while the rs 1800450 and rs11003125 polymorphism was consistent with Hardy-Weinberg expectations in both the case and the control groups. Genotypes and allele frequencies of rs1800450 as well as rs11003125 were observed （P = 0.006, P = 0.003 ） and （P = 0.010, P= 0.004）, respectively. Data from logistic regression analysis revealed that factors as overweight, abdominal obesity, hypercholesterolemia, GG genotype frequencies of Exonl rs1800450 polymorphism as well as （GC ＋ CC） genotype frequencies of rs11003125 polymorphism in MBL2 conferred increased risks for type 2 diabetes. Haplotype analyses of the two SNPs （rs1800450, rs11003125） revealed similar effects as compared with the single SNP associations. Only haplotype constructed from GC alleles conferred increased trends for type 2 diabetes （OR=2.21, 95% CI： 1.47-3.33, P=0.000）. Conclusion Our result suggested that the Exonl rs1800450 polymorphism and promoter region rs11003125 polymorphism in MBL2 gene were both associated with type 2 diabetes in the Chinese population living in the northern areas of China. The G allele of rs 1800450 and C allele of rs 11003125 might be the risk factors of type 2 diabetes.