title: Association of cystic fibrosis transmembrane conductance regulator (CFTR) mutation/variant/haplotype and tumor necrosis factor (TNF) promoter polymorphism in hyperlipidemic pancreatitis.
abstract: BACKGROUND
  The mechanism by which hypertriglyceridemia (HTG) leads to pancreatitis is not clear. We sought to determine whether the genes involved in pancreatic ductal or acinar cell injury, including the cationic trypsinogen gene [protease, serine, 1 (trypsin 1) (PRSS1)], the pancreatic secretory trypsin inhibitor gene [serine peptidase inhibitor, Kazal type 1 (SPINK1)], the cystic fibrosis transmembrane conductance regulator gene [cystic fibrosis transmembrane conductance regulator (ATP-binding cassette subfamily C, member 7) (CFTR)], and inflammation genes such as tumor necrosis factor [tumor necrosis factor, TNF superfamily, member 2 (TNF)] are associated with hyperlipidemic pancreatitis (HLP) in patients with HTG.
  
  
  METHODS
  We performed genetic analysis of 126 HTG patients in Taiwan (46 with HLP and 80 without HLP). The entire coding and intronic regions of the PRSS1, SPINK1, and CFTR genes were identified by heteroduplex analysis techniques and were confirmed by sequencing analysis. The presence of 125G/C, 1001 + 11C>T, 1540A>G (Met470Val), 2694T>G, and 4521G>A in CFTR, the presence of 272C>T in SPINK1, and TNF promoter polymorphisms (nucleotide positions 1031, 863, 857, 308, and 308) were measured by direct sequencing.
  
  
  RESULTS
  Of the 126 HTG patients, 13 (10.3%) carried a CFTR mutation. No PRSS1 or SPINK1 mutations were detected in our patients or in HTG controls. The CFTR gene mutation rates in HTG with and without HLP were 26.1% (12 of 46) and 1.3% (1 of 80), respectively (P <0.0001). The CFTR gene mutations were all Ile556Val. A multivariate analysis of HTG patients indicated that triglycerides, CFTR 470Val, and TNF promoter 863A were independent risk markers for HLP.
  
  
  CONCLUSIONS
  This genetic study is the first one to address the association of HLP with the CFTR mutation/variant/haplotype and TNF promoter polymorphism in a Chinese HTG population. The results suggest that the occurrence of HLP is multifactorial and polygenic.
authors.affiliation: Department of Internal Medicine, College of Medicine, National Taiwan University, National Taiwan University Hospital, No. 7 Chung Shan South Road, Taipei, Taiwan.
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Chang
authors.forename: Ming-Chu
authors.initials: MC
authors.lastname: Chang
authors.forename: Ta-Chen
authors.initials: TC
authors.lastname: Su
authors.forename: Po-Chin
authors.initials: PC
authors.lastname: Liang
authors.forename: Yi-Ning
authors.initials: YN
authors.lastname: Su
authors.forename: Chun-Hung
authors.initials: CH
authors.lastname: Kuo
authors.forename: Shu-Chen
authors.initials: SC
authors.lastname: Wei
authors.forename: Jau-Min
authors.initials: JM
authors.lastname: Wong
mesh_terms: D000328:Adult; D044466:Asian People; D002352:Carrier Proteins / Q000235:genetics; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D006949:Hyperlipidemias / Q000150:complications / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010195:Pancreatitis / Q000209:etiology / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D014357:Trypsin; D014359:Trypsin Inhibitor, Kazal Pancreatic; D014362:Trypsinogen / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; C486642:SPINK1 protein, human; D014409:Tumor Necrosis Factor-alpha; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D014359:Trypsin Inhibitor, Kazal Pancreatic; D014362:Trypsinogen; C489303:PRSS1 protein, human; D014357:Trypsin