Mutations in the lipoprotein lipase gene as a cause of hypertriglyceridemia and pancreatitis in Taiwan.
BACKGROUND
Familial lipoprotein lipase (LPL) deficiency is inherited as an autosomal recessive trait and is characterized by chylomicronemia, eruptive xanthoma, hepatosplenomegaly, and recurrent pancreatitis.


OBJECTIVE
Two unrelated Chinese of Han descent with hypertriglyceridemia were enrolled in this study, and another six Han Chinese with no family history of hypertriglyceridemia and diabetes were recruited as normal controls. LPL activity was determined with use of an artificial substrate of 14C-trioleine and Arabic gum, and release of 14C free fatty acid was determined by the liquid-liquid partitioning system. LPL mass was measured by enzyme immunoassay. Genomic DNA was extracted from EDTA-preserved whole blood, and PCR was used to amplify the nine coding exons and the minimal promoter of the LPL gene.


RESULTS
DNA sequence analysis revealed that mutations were identified in both patients; one patient had compound heterozygous mutations in codon 252 [CTG(Leu) --> GTG(Val)] and in codon 264 [TGC(Cys) --> TGa(Ter)] of exon 6, and the other patient had homozygous L252V mutation. These subjects had > or =90% reduction in LPL mass and > or =60% reduction in LPL activity.


CONCLUSIONS
The mutated and truncated LPLs caused hypertriglyceridemia in these patients in Taiwan with hypertriglyceridemia and pancreatitis.
Jap
Tjin-Shing
TS
Section of Biochemistry, Department of Pathology and Laboratory Medicine, Veterans General Hospital-Taipei, Taiwan, ROC. tsjap@vghtpe.gov.tw
Jenq
Shwu-Fen
SF
Wu
Yi-Chi
YC
Chiu
Chih-Yang
CY
Cheng
Hon-Mei
HM
D000328:Adult; D001483:Base Sequence; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D006801:Humans; D015228:Hypertriglyceridemia / Q000235:genetics / Q000473:pathology*; D008071:Lipoprotein Lipase / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010195:Pancreatitis / Q000235:genetics / Q000473:pathology*; D010375:Pedigree; D011110:Polymorphism, Genetic; D012008:Recurrence; D013624:Taiwan
D004247:DNA; D008071:Lipoprotein Lipase