Lipoprotein lipase mutation S447X associated with pancreatic calcification and steatorrhea in hyperlipidemic pancreatitis.
BACKGROUND
The factors that whether and how genes involving lipid metabolism including lipoprotein lipase (LPL) and apolipoprotein CII (apo CII) influence occurrence of acute attack of pancreatitis and chronic pancreatitis is not clear.


OBJECTIVE
The aim of this study was to determine the association of LPL and apo CII genes with acute attack of pancreatitis and chronic pancreatitis in patients with hyperlipidemic pancreatitis (HLP) and hypertriglyceridemia (HTG).


METHODS
We performed genetic analysis of 134 patients in Taiwan with HTG (53 with HLP and 81 without HLP). The entire coding and intronic regions of the LPL and apo CII genes were identified with heteroduplex analytical techniques or high resolution melting analysis. All mutations were confirmed by sequencing analysis. Correlation of phenotype and genotype was also analyzed.


RESULTS
The frequency of LPL gene mutation rates in HLP patients (17.0%, 9 of 53) was significantly higher than that without HLP attack (4.9%, 4 of 81) (P<0.0001). A total of 10.4% (14 of 134) of our HTG patients carried LPL or apo CII mutation. The most common LPL gene mutation was S447X. There is a high prevalence (77.8%) of HLP attack in HTG patients carrying S447X mutation. Multivariate analysis in HLP patients indicated that the presence of LPL mutation and episode of acute attack were independent risks for pancreatic calcification and steatorrhea.


CONCLUSIONS
This is the first complete genetic study analyzing the association of LPL and apo CII mutation in a HLP population. LPL S447X mutation is associated with a higher risk of pancreatic calcification and steatorrhea than those previously known factors in HLP patients.
Chang
Yu-Ting
YT
Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.
Chang
Ming-Chu
MC
Su
Ta-Chen
TC
Liang
Po-Chin
PC
Su
Yi-Ning
YN
Kuo
Chun-Hung
CH
Wei
Shu-Chen
SC
Wong
Jau-Min
JM
D000328:Adult; D053304:Apolipoprotein C-II / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D006949:Hyperlipidemias / Q000235:genetics* / Q000473:pathology; D015228:Hypertriglyceridemia / Q000235:genetics / Q000473:pathology; D008071:Lipoprotein Lipase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010179:Pancreas / Q000473:pathology; D010195:Pancreatitis / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D045602:Steatorrhea / Q000235:genetics; D013624:Taiwan
D053304:Apolipoprotein C-II; D008071:Lipoprotein Lipase