ApoAI-CⅢ-AIV基因簇多态性对痛风伴胰岛素抵抗患者高脂血症的作用

The Role of the Polymorphisms of the Apolipoprotein AI-CⅢ-AIV Gene Cluster for Hyperlipidemia in Gout with Insulin Resistance

[目的]研究痛风伴胰岛素抵抗相关基因载脂蛋白AI-CⅢ-AIV(ApoAI-CⅢ-AIV)多态性,探讨该基因簇多态性对痛风伴胰岛素抵抗患者高脂血症的影响。[方法]痛风及痛风伴胰岛素抵抗病例均来自2008年2～12月在山东省随机选取的5个医院内科确诊的患者(分别为55、52例),同时,选取同期在该医院内科体检的健康志愿者作为对照(48人)。3组年龄、性别等经统计学分析无明显差异。应用多聚酶链反应、限制性片段长度多态性技术(PCR-RFLP)及生化分析方法,探讨ApoAI-CⅢ-AIV基因簇不同基因型与基因频率的分布,以及基因突变与血脂之间的相关,分析痛风伴胰岛素抵抗患者高脂血症与ApoAI-CⅢ-AIV基因簇之间的关系。[结果]痛风伴胰岛素抵抗患者血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、血尿酸(SUA)、血糖(FBG)及血浆胰岛素(FNS)水平高于痛风患者及健康志愿者(P<0.05或<0.01)。痛风伴胰岛素抵抗患者ApoAI-CⅢ-AIV基因簇-75位点A、+83位点T等位基因的频率及Xmn I位点突变型等位基因X2的频率较健康志愿者明显增高(P<0.05)。ApoAI-CⅢ-AIV基因簇MspI 1位点具有A/A基因型者血清TG、高密度脂蛋白胆固醇(HDL-C)及载脂蛋白AI(ApoAI)水平较具有G/G基因型者显著升高,ApoAI-CⅢ-AIV基因簇XmnI位点具有X2X2基因型者血清TG水平较具有X1X1基因型者为高(P<0.05)。痛风伴胰岛素抵抗患者TG水平升高是MspI 1位点A等位基因及XmnI位点X2等位基因两个多态位点联合作用的结果。[结论]痛风伴胰岛素抵抗患者ApoAI-CⅢ-AIV基因簇基因型和等位基因变化导致脂蛋白水平等相应改变,且与两个多态位点的协同效应有关。该基因簇与痛风伴胰岛素抵抗密切相关,提示痛风患者应积极预防控制代谢综合征相关疾病的发生发展和相互作用。

[Objective]To study the polymorphisms of the apolipoprotein AI-CⅢ-AIV gene cluster in gout with insulin resistance and explore the impact of the ApoAI-C Ⅲ-AIV gene cluster on hyperlipidemia in gout with insulin resistance. [Methods]The cases in gout and gout with insulin resistance were from 5 hospitals in Shandong province during February- December,2008,and selecting healthy volunteers who undergowent a medical examination in the hospital in the identical time as a control. Three groups had no significant difference in age,gender etc. by statistical analysis. PCR-RELP and biochemistry methods were used to explore the distribution of different genotypes and gene frequencies of ApoAI-CⅢ-AIV gene cluster, to investigate the correlation between the gene mutation and blood lipids, and analyze the relationship between hyperlipidemia in gout with insulin resistance and ApoAI-CⅢ-AIV gene cluster. [Results]The patients of gout with insulin resistance had a significantly higher serum levels of TC, TG and LDL-CⅢ and higher serum concentrations of SUA, FBG and FNS compared with the subjects of gout and healthy volunteer（ P 〈0.05 or 〈0.01）. The A allele at position -75 bp and the T allele at position ＋83 hp in the ApoAI-CⅢ-AIV gene cluster were more common in gout with insulin resistance than those in controls（ P %0.05）. The X2 allele at Xmn I sites of ApoAI-CⅢ-AIV＇ gene cluster was more in gout with insulin resistance than that in controls（ P %0.05）. The levels of serum TG, HDL-C and apoAI in MspI 1 site with A/A genotyp were significantly higher than those with the genotype G/G（ P %0.05）. The levels of serum TG in Xmn I site with X2X2 genotvD were higher than that with X1 X1 genotvDe（ P d0.05）. Higher levels of TG in gout with insulin resistance was result that the A allele at position MspI 1 and the X2 alele at Xmn I sites combined operations. [Conclusion] The genotype and allele change of the apolipoprotein AI- CⅢ-AIV gene cluster in gout with insulin resistance result in change of lipoprotein levels etc. It is related to combined operations of two genotypes. The results suggest that the ApoAI-CⅢ-AIV gene cluster is closely related to gout with insulin resistance. Prompted gout patients should actively prevent and control the development and interaction of the occurrence of the metabolic syndrome related diseases.