Shin H D, Park K S, Park B L, Cheong H S, Cho Y M, Lee H K, Lee J-Y, Lee J-K, Kim H T, Han B G, Kim J W, Koh I, Kim Y J, Oh B, Kimm K, Park C
Department of Genetic Epidemiology, SNP Genetics, Inc., Seoul, Korea.
Diabet Med. 2006 Jan;23(1):72-6. doi: 10.1111/j.1464-5491.2005.01732.x.
Growing evidence supports the hypothesis that chronic low-grade inflammation related to innate immunity may play an important role in the pathophysiology of Type 2 diabetes mellitus (T2DM). The monocyte differentiation antigen CD14 gene (CD14) acts as the receptor for lipopolysaccharide (LPS) and augments monocyte/macrophage inflammatory responses.
We have sequenced the gene, including all exons, exon/intron boundaries, and the -1.5 kb of the 5' flanking region. Two common loci (minor allele frequency > 0.05) were genotyped in 775 T2DM patients and 316 control subjects recruited in the Korean T2DM Study.
Eight polymorphisms, including four non-synonymous forms, were identified in CD14. No polymorphisms were found in association with T2DM. However, one common promoter SNP (-260T>C) was significantly associated with both the serum triglyceride level (TG) and body mass index (BMI) in non-diabetic control subjects. Individuals who carried the minor allele (C) had higher TG levels (1.65 +/- 0.81 vs. 1.46 +/- 0.80 mmol/l; P = 0.0007) and BMI (23.96 +/- 3.00 vs. 23.28 +/- 3.22 kg/m(2); P = 0.04) as compared with subjects carrying T/T genotypes.
Our data suggest that lipid metabolism and obesity, important pathophysiological elements of T2DM and the metabolic syndrome, are regulated by complex mechanisms that include the CD14 gene polymorphism-mediated genetic propensity to non-specific inflammatory responses.
越来越多的证据支持这样一种假说，即与先天免疫相关的慢性低度炎症可能在2型糖尿病（T2DM）的病理生理学中起重要作用。单核细胞分化抗原CD14基因（CD14）作为脂多糖（LPS）的受体，可增强单核细胞/巨噬细胞的炎症反应。
我们对该基因进行了测序，包括所有外显子、外显子/内含子边界以及5'侧翼区域的-1.5 kb。在韩国T2DM研究中招募的775例T2DM患者和316例对照受试者中，对两个常见位点（次要等位基因频率>0.05）进行了基因分型。
在CD14中鉴定出8种多态性，包括4种非同义形式。未发现与T2DM相关的多态性。然而，一个常见的启动子单核苷酸多态性（-260T>C）在非糖尿病对照受试者中与血清甘油三酯水平（TG）和体重指数（BMI）均显著相关。与携带T/T基因型的受试者相比，携带次要等位基因（C）的个体TG水平更高（1.65±0.81 vs. 1.46±0.80 mmol/l；P = 0.0007），BMI更高（23.96±3.00 vs. 23.28±3.22 kg/m²；P = 0.04）。
我们的数据表明，脂质代谢和肥胖是T2DM和代谢综合征的重要病理生理因素，它们受复杂机制调节，其中包括CD14基因多态性介导的对非特异性炎症反应的遗传倾向。
