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首页> 外文期刊>Cell metabolism >Heterozygosity for a loss-of-function mutation in GALNT2 improves plasma triglyceride clearance in man.
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Heterozygosity for a loss-of-function mutation in GALNT2 improves plasma triglyceride clearance in man.

机译：GALNT2中功能丧失突变的杂合性改善了人血浆甘油三酸酯的清除率。

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摘要

Genome-wide association studies have identified GALNT2 as a candidate gene in lipid metabolism, but it is not known how the encoded enzyme ppGalNAc-T2, which contributes to the initiation of mucin-type O-linked glycosylation, mediates this effect. In two probands with elevated plasma high-density lipoprotein cholesterol and reduced triglycerides, we identified a mutation in GALNT2. It is shown that carriers have improved postprandial triglyceride clearance, which is likely attributable to attenuated glycosylation of apolipoprotein (apo) C-III, as observed in their plasma. This protein inhibits lipoprotein lipase (LPL), which hydrolyses plasma triglycerides. We show that an apoC-III-based peptide is a substrate for ppGalNAc-T2 while its glycosylation by the mutant enzyme is impaired. In addition, neuraminidase treatment of apoC-III which removes the sialic acids from its glycan chain decreases its potential to inhibit LPL. Combined, these data suggest that ppGalNAc-T2 can affect lipid metabolism through apoC-III glycosylation, thereby establishing GALNT2 as a lipid-modifying gene.
机译：全基因组关联研究已确定GALNT2是脂质代谢中的候选基因，但尚不清楚编码的酶ppGalNAc-T2如何介导粘蛋白型O型糖基化的介导介导这种作用。在血浆高密度脂蛋白胆固醇升高和甘油三酯降低的两个先证者中，我们发现了GALNT2中的突变。结果表明，如在血浆中观察到的，载体具有改善的餐后甘油三酯清除率，这很可能归因于载脂蛋白（apo）C-III的糖基化减弱。该蛋白质抑制脂蛋白脂肪酶（LPL），后者可水解血浆甘油三酸酯。我们显示，基于apoC-III的肽是ppGalNAc-T2的底物，而其突变酶的糖基化作用受损。另外，apoC-III的神经氨酸酶处理可从其聚糖链中除去唾液酸，从而降低了其抑制LPL的潜力。综合来看，这些数据表明ppGalNAc-T2可通过apoC-III糖基化影响脂质代谢，从而将GALNT2建立为脂质修饰基因。

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