Yang Yuhong, Mu Yunxiang, Zhao Yu, Liu Xinyu, Zhao Lili, Wang Junmei, Xie Yonghong
Department of Biochemistry, Tianjin Medical University, Tianjin 300070, China.
J Genet Genomics. 2007 May;34(5):381-91. doi: 10.1016/S1673-8527(07)60041-1.
To investigate the association between the mutations in lipoprotein lipase gene and hypertriglyceridemia (HTG).
The lipoprotein lipase (LPL) gene was screened for mutations in 386 Chinese subjects with (108 cases in the HTG group) or without HTG (278 cases in the control group), by single-strand conformation polymorphism (SSCP) analysis and DNA sequencing.
One novel silent mutation L103L, one missense mutation P207L, three splicing mutations Int3/3'-ass/C(-6) --> T, and the common S447X polymorphism has been identified in the whole coding region and exon-intron junctions of the LPL gene were examined. Heterozygous P207L found in the HTG group was the first case reported in Asia and subsequently another P207L heterozygote was found in the proband's family, all of which suggested that P207L was one of the causes of familial combined hyperlipidemia, but was not so prevalent as that in French Canadian. Int3/3'-ass/C(-6) --> T was found in both groups in the present study although it was regarded as a pathogenic variant to HTG earlier on. Moreover about the beneficial polymorphism S447X, there was also some supportive evidence that the levels of triglycerides (TG) in S447X carriers were significantly lower than noncarriers in the subjects without HTG.
The association between the LPL variants and HTG is quite complicated and versatile, genotyping of LPL in a larger-scale screening should be necessary and justifiable.
探讨脂蛋白脂肪酶基因突变与高甘油三酯血症（HTG）之间的关联。
采用单链构象多态性（SSCP）分析和DNA测序技术，对386名有（HTG组108例）或无HTG（对照组278例）的中国受试者的脂蛋白脂肪酶（LPL）基因进行突变筛查。
在LPL基因的整个编码区和外显子-内含子连接处检测到一个新的沉默突变L103L、一个错义突变P207L、三个剪接突变Int3/3'-ass/C(-6)→T以及常见的S447X多态性。HTG组中发现的杂合子P207L是亚洲报道的首例，随后在先证者家族中又发现了另一例P207L杂合子，所有这些表明P207L是家族性混合性高脂血症的病因之一，但不如法裔加拿大人中那么普遍。本研究中在两组中均发现了Int3/3'-ass/C(-6)→T，尽管它之前被认为是HTG的致病变异。此外，关于有益的多态性S447X，也有一些支持性证据表明，在无HTG的受试者中，S447X携带者的甘油三酯（TG）水平显著低于非携带者。
LPL变异与HTG之间的关联相当复杂且多样，在更大规模的筛查中对LPL进行基因分型是必要且合理的。
