Department of Internal Medicine, University of Genoa, Viale Benedetto XV n. 6, 16132 Genoa, Italy.
Clin Chim Acta. 2011 Nov 20;412(23-24):2194-8. doi: 10.1016/j.cca.2011.08.001. Epub 2011 Aug 7.
Common variants of APOA5 gene affect plasma triglyceride (TG) in the population and a number of rare variants APOA5 have been reported in individuals with hypertriglyceridemia (HTG).
APOA5 was analysed in 98 HTG individuals (plasma TG >9 mmol/L) in whom no mutations in LPL and APOC2 had been found.
Two patients were found to be heterozygous for two novel APOA5 variants. The first variant (p.L253P) was identified in an obese male who consumed a diet rich in fat and simple sugars. He was also a carrier in trans of the common TG-raising p.S19W SNP (53 haplotype). The second variant (c.295-297 del GAG, p.E99 del) was found in a lean male with no life style or metabolic factors known to affect plasma TG. He was a carrier in trans of the TG-raising 52 haplotype and was homozygous for the rare c.1337T allele of a SNP of GCKR gene. No mutations in other genes affecting plasma TG (LMF1 and GPIHBP1) were found in these patients. These APOA5 variants, resulted to be deleterious in silico, were not found in 350 control subjects.
These novel APOA5 variants predispose to HTG in combination with other genetic or nutritional factors.
APOA5 基因的常见变异会影响人群中的血浆甘油三酯（TG）水平，并且已经在高甘油三酯血症（HTG）个体中报道了许多罕见的 APOA5 变异。
在 98 名 HTG 个体（血浆 TG >9 mmol/L）中分析了 APOA5，这些个体中未发现 LPL 和 APOC2 的突变。
发现两名患者为两种新的 APOA5 变异的杂合子。第一个变异（p.L253P）发生在一位肥胖男性身上，他食用富含脂肪和简单糖的饮食。他也是常见的 TG 升高 p.S19W SNP（53 单倍型）的携带者。第二个变异（c.295-297delGAG，p.E99del）发生在一位消瘦的男性身上，没有已知的影响血浆 TG 的生活方式或代谢因素。他是 TG 升高的 52 单倍型的携带者，并且是 GCKR 基因 SNP 的罕见 c.1337T 等位基因的纯合子。在这些患者中没有发现影响血浆 TG 的其他基因（LMF1 和 GPIHBP1）的突变。这些 APOA5 变异在计算机模拟中被认为是有害的，在 350 名对照中未发现。
这些新的 APOA5 变异与其他遗传或营养因素一起导致 HTG 易感性。
