Apolipoprotein M gene (APOM) polymorphism modifies metabolic and disease traits in type 2 diabetes.
Apolipoprotein M gene (APOM) polymorphism modifies metabolic and disease traits in type 2 diabetes.
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DOI：
10.1371/journal.pone.0017324
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发表时间：
2011-02-24
期刊：
影响因子：
3.7
通讯作者：
Ho YY
中科院分区：
文献类型：
--
作者：
Zhou JW;Tsui SK;Ng MC;Geng H;Li SK;So WY;Ma RC;Wang Y;Tao Q;Chen ZY;Chan JC;Ho YY
本研究的目的是证实载脂蛋白M基因（APOM）与2型糖尿病（T2D）以及与代谢性状的关系。此外，APOM基因的功能进行了进一步表征，以阐明其在胆固醇代谢中的活性。对NCBI数据库中记录的17个APOM SNP进行基因分型。在我们的1234名T2D和606名对照参与者的研究队列中确认了5个SNP。5个SNPs中有3个处于连锁不平衡（LD）状态，分别为rs707921（C+1871A）、rs707922（G+1837T）和rs805264（G+203A）。我们选择rs707922标记该LD区域用于下游关联分析，并在分子水平上表征该SNP的功能。在我们的中国香港队列中未检测到APOM与T2D易感性之间的关联。有趣的是，rs805297的C等位基因与超过10年的T2D持续时间显著相关（OR = 1.245，p = 0.015）。 在T2D患者中，rs707922 TT基因型与血浆总胆固醇和LDL胆固醇水平升高显著相关（分别为p = 0.006和p =0.009）。 对rs707922的分子分析发现了一种新型转录本APOM5以及该基因第5号外显子的神秘性质。APOM 5转录本的异位表达证实了转录本在体外改变胆固醇稳态中的rs707922等位基因依赖性活性。因此，本研究结果不支持APOM是中国香港地区T2D易感基因。然而，在T2D患者中，APOM SNP的子集与疾病持续时间和代谢特征相关。进一步的分子生物学分析证实了rs707922在APOM表达和调节细胞胆固醇含量中的功能活性。
This study aimed at substantiating the associations of the apolipoproein M gene (APOM) with type 2 diabetes (T2D) as well as with metabolic traits in Hong Kong Chinese. In addition, APOM gene function was further characterized to elucidate its activity in cholesterol metabolism. Seventeen APOM SNPs documented in the NCBI database were genotyped. Five SNPs were confirmed in our study cohort of 1234 T2D and 606 control participants. Three of the five SNPs rs707921(C+1871A), rs707922(G+1837T) and rs805264(G+203A) were in linkage disequilibrium (LD). We chose rs707922 to tag this LD region for down stream association analyses and characterized the function of this SNP at molecular level. No association between APOM and T2D susceptibility was detected in our Hong Kong Chinese cohort. Interestingly, the C allele of rs805297 was significantly associated with T2D duration of longer than 10 years (OR = 1.245, p = 0.015). The rs707922 TT genotype was significantly associated with elevated plasma total- and LDL- cholesterol levels (p = 0.006 and p = 0.009, respectively) in T2D patients. Molecular analyses of rs707922 lead to the discoveries of a novel transcript APOM5 as well as the cryptic nature of exon 5 of the gene. Ectopic expression of APOM5 transcript confirmed rs707922 allele-dependent activity of the transcript in modifying cholesterol homeostasis in vitro. In conclusion, the results here did not support APOM as a T2D susceptibility gene in Hong Kong Chinese. However, in T2D patients, a subset of APOM SNPs was associated with disease duration and metabolic traits. Further molecular analysis proved the functional activity of rs707922 in APOM expression and in regulation of cellular cholesterol content.
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