Abstract:
AIM:To investigate whether the patatin-like phospholipase domain containing-3 gene (PNPLA3) I148M polymorphism is associated with steatosis, fibrosis stage, and cirrhosis in hereditary hemochromatosis (HH). METHODS:We studied 174 consecutive unrelated homozygous for the C282Y HFE mutation of HH (C282Y+/+ HH) patients from Northern Italy, for whom the presence of cirrhosis could be determined based on histological or clinical criteria, without excessive alcohol intake (< 30/20 g/d in males or females) or hepatitis B virus and hepatitis C virus viral hepatitis. Steatosis was evaluated in 123 patients by histology (n = 100) or ultrasound (n = 23). The PNPLA3 rs738409 single nucleotide polymorphism, encoding for the p.148M protein variant, was genotyped by a Taqman assay (assay on demand, Applied Biosystems). The association of the PNPLA3 I148M protein variant (p.I148M) with steatosis, fibrosis stage, and cirrhosis was evaluated by logistic regression analysis. RESULTS:PNPLA3 genotype was not associated with metabolic parameters, including body mass index (BMI), the presence of diabetes, and lipid levels, but the presence of the p.148M variant at risk was independently associated with steatosis [odds ratio (OR) 1.84 per p.148M allele, 95% confidence interval (CI): 1.05-3.31; P = 0.037], independently of BMI and alanine aminotransaminase (ALT) levels. The p.148M variant was also associated with higher aspartate aminotransferase (P = 0.0014) and ALT levels (P = 0.017) at diagnosis, independently of BMI and the severity of iron overload. In patients with liver biopsy, the 148M variant was independently associated with the severity (stage) of fibrosis (estimated coefficient 0.56 ± 0.27, P = 0.041). In the overall series of patients, the p.148M variant was associated with cirrhosis in lean (P = 0.049), but not in overweight patients (P = not significant). At logistic regression analysis, cirrhosis was associated with BMI ≥ 25 (OR 1.82, 95% CI: 1.02-3.55), ferritin > 1000 ng/mL at diagnosis (OR 19.3, 95% CI: 5.3-125), and with the G allele in patients with BMI < 25 (OR 3.26, 95% CI: 1.3-10.3). CONCLUSION:The PNPLA3 I148M polymorphism may represent a permissive factor for fibrosis progression in patients with C282Y+/+ HH.
journal_name
World J Gastroenteroljournal_title
World journal of gastroenterologyauthors
Valenti L,Maggioni P,Piperno A,Rametta R,Pelucchi S,Mariani R,Dongiovanni P,Fracanzani AL,Fargion Sdoi
10.3748/wjg.v18.i22.2813subject
Has Abstractpub_date
2012-06-14 00:00:00pages
2813-20issue
22eissn
1007-9327issn
2219-2840journal_volume
18pub_type
杂志文章abstract:AIM:To retrospectively analyze factors affecting the long-term survival of patients with pancreatic cancer who underwent pancreatic resection. METHODS:From January 2000 to December 2011, 195 patients underwent pancreatic resection in our hospital. The prognostic factors after pancreatic resection were analyzed in all ...
journal_title:World journal of gastroenterology
pub_type: 杂志文章
doi:10.3748/wjg.v21.i1.262
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journal_title:World journal of gastroenterology
pub_type: 杂志文章
doi:10.3748/wjg.v11.i19.2927
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pub_type: 杂志文章
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journal_title:World journal of gastroenterology
pub_type: 杂志文章
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pub_type: 杂志文章,评审
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pub_type: 杂志文章,评审
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journal_title:World journal of gastroenterology
pub_type: 杂志文章
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journal_title:World journal of gastroenterology
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journal_title:World journal of gastroenterology
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pub_type: 杂志文章,meta分析,评审
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pub_type: 杂志文章,评审
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journal_title:World journal of gastroenterology
pub_type: 杂志文章,评审
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更新日期:2013-04-07 00:00:00
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pub_type: 杂志文章
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journal_title:World journal of gastroenterology
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pub_type: 杂志文章
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更新日期:2014-04-28 00:00:00
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journal_title:World journal of gastroenterology
pub_type: 杂志文章
doi:10.3748/wjg.v18.i9.915
更新日期:2012-03-07 00:00:00
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journal_title:World journal of gastroenterology
pub_type: 杂志文章
doi:10.3748/wjg.v24.i1.35
更新日期:2018-01-07 00:00:00
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journal_title:World journal of gastroenterology
pub_type: 杂志文章
doi:10.3748/wjg.v23.i1.48
更新日期:2017-01-07 00:00:00
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journal_title:World journal of gastroenterology
pub_type: 杂志文章
doi:10.3748/wjg.v17.i19.2407
更新日期:2011-05-21 00:00:00
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journal_title:World journal of gastroenterology
pub_type: 临床试验,杂志文章
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更新日期:2008-03-21 00:00:00
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journal_title:World journal of gastroenterology
pub_type: 杂志文章
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更新日期:2008-03-28 00:00:00
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journal_title:World journal of gastroenterology
pub_type: 杂志文章
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更新日期:2008-05-14 00:00:00
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journal_title:World journal of gastroenterology
pub_type: 评论,杂志文章
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更新日期:2015-03-14 00:00:00
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journal_title:World journal of gastroenterology
pub_type: 杂志文章
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更新日期:2004-08-15 00:00:00