The PNPLA3 rs738409 C &gt; G polymorphism is associated with the risk of progression to cirrhosis in NAFLD patients

Gentilucci, Umberto Vespasiani; Gallo, Paolo; Porcari, Aldostefano; Carotti, Simone; Galati, Giovanni; Piccioni, Livia; Vincentis, Antonio De; Dell’Unto, C.; Vorini, Ferruccio; Morini, Sergio; Riva, Elisabetta; Picardi, Antonio

doi:10.3109/00365521.2016.1161066

Cited by 24 publications

(15 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Indeed, the I148M variant has been associated with the degree of hepatic injury and all the histopathological aspects of NAFLD, including the presence of NASH, fibrosis, and development of HCC [ 5 , 22 ]. More recently, we have reported that the rs738409 PNPLA3 SNP is associated not only generically with NAFLD fibrosis but also specifically with the evolution to NASH cirrhosis [ 23 ]. To date, the rs58542926 SNP in the TM6SF2 locus should be considered in the second place of importance.…”

Section: Discussionmentioning

confidence: 99%

Combining Genetic Variants to Improve Risk Prediction for NAFLD and Its Progression to Cirrhosis: A Proof of Concept Study

Gentilucci

Dell’Unto

Vincentis

et al. 2018

Canadian Journal of Gastroenterology and Hepatology

Self Cite

View full text Add to dashboard Cite

Background & Aims Identifying NAFLD patients at risk of progression is crucial to orient medical care and resources. We aimed to verify if the effects determined by different single nucleotide polymorphisms (SNPs) could add up to multiply the risk of NAFLD and NASH-cirrhosis. Methods Three study populations, that is, patients diagnosed with NASH-cirrhosis or with noncirrhotic NAFLD and healthy controls, were enrolled. PNPLA3 rs738409, TM6SF2 rs58542926, KLF6 rs3750861, SOD2 rs4880, and LPIN1 rs13412852 were genotyped. Results One hundred and seven NASH-cirrhotics, 93 noncirrhotic NAFLD, and 90 controls were enrolled. At least one difference in allele frequency between groups was significant, or nearly significant, for the PNPLA3, TM6SF2, and KLF6 variants (p < 0.001, p < 0.05, and p = 0.06, resp.), and a risk score based on these SNPs was generated. No differences were observed for SOD2 and LPIN1 SNPs. When compared to a score of 0, a score of 1-2 quadrupled, and a score of 3-4 increased 20-fold the risk of noncirrhotic NAFLD; a score of 3-4 quadrupled the risk of NASH-cirrhosis. Conclusions The effects determined by disease-associated variants at different loci can add up to multiply the risk of NAFLD and NASH-cirrhosis. Combining different disease-associated variants may represent the way for genetics to keep strength in NAFLD diagnostics.

show abstract

Section: Discussionmentioning

confidence: 99%

Combining Genetic Variants to Improve Risk Prediction for NAFLD and Its Progression to Cirrhosis: A Proof of Concept Study

Gentilucci

Dell’Unto

Vincentis

et al. 2018

Canadian Journal of Gastroenterology and Hepatology

Self Cite

View full text Add to dashboard Cite

show abstract

“… 2015 China 11.81 ± 2.20 11.44 ± 2.99 162 865 23 Uygun, A [ 42 ]. 2017 Turkey 42.1 ± 11.4 34.1 ± 12.8 216 150 24 Valenti, L. [ 43 ] 2012 Italy 49.5 ± 12 48(1 ± 2 144 257 25 Valenti, L. [ 44 ] 2010 Italy 46.4 ± 11 48.4 ± 13 253 179 26 Vespasiani-Gentilucci, U [ 45 ]. 2016 Italy 51.5 ± 12.3 40.1 ± 13.1 60 125 27 Wang, C. W [ 18 ].…”

Section: Resultsmentioning

confidence: 99%

Association between PNPLA3 rs738409 polymorphism and nonalcoholic fatty liver disease: a systematic review and meta-analysis

et al. 2021

View full text Add to dashboard Cite

Background Non-alcoholic fatty liver disease (NAFLD) is a common disorder that is known to be the leading cause of chronic liver disease worldwide. This study aims to systematically review and meta-analyze the association between PNPLA3 rs738409 polymorphism and non-alcoholic fatty liver. Methods Following a systematic review and meta-analysis method, articles without any time limitation, were extracted from SID, MagIran, IranDoc, Scopus, Embase, Web of Science (WoS), PubMed and ScienceDirect international databases. Random effects model was used for analysis, and heterogeneity of studies was investigated considering the I2 index and using Comprehensive Meta-Analysis software. Results The odds ratio of CC genotype in patients with non-alcoholic fatty liver demonstrates the protective effect of CC genotype with the ratio of 0.52, whereas CG genotype presents an increasing effect of CG genotype with the ratio of 0.19, and GG genotype also showed an increasing effect of GG genotype with the ratio of 1.05. Moreover, CG + GG genotypes as a single group demostrated an odds rartio of 0.88. Conclusion This meta-analysis highlights that people with CC genotype has 52% lower chance of developing non-alcoholic fatty liver disease, and those with CG genotype had 19% higher risk of developing non-alcoholic fatty liver. Those with GG genotype were 105% more likely to develop non-alcoholic fatty liver than others. Moreover, those present in a population with CG + GG genotypes were 88% more likely to have non-alcoholic fatty liver disease.

show abstract

“…[ 18 ] Additionally, recent studies revealed that this polymorphism was also associated with liver damage diseases such as NASH, fibrosis, cirrhosis, and hepatocellular carcinoma. [ 8 , 12 , 21 , 22 , 24 , 39 ] In order to show the involvement of rs738409 in other liver damages in our cohort, further studies are required with a larger group of patients and controls.…”

Section: Discussionmentioning

confidence: 99%

The influence of RS738409 I148M polymorphism of patatin-like phospholipase domain containing 3 gene on the susceptibility of non-alcoholic fatty liver disease

et al. 2021

View full text Add to dashboard Cite

We aimed to elucidate the frequency of polymorphic genotypes and alleles of patatin-like phospholipase domain containing 3 rs738409 polymorphism and its possible associations with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis in a cohort from Turkey. We enrolled 200 patients diagnosed with NAFLD and genotyped for rs738409 I148M polymorphism by real-time polymerase chain reaction, particularly by melting curve analysis. SPSS analysis software was used for statistical significance. Continuous variable values were expressed as mean ± standard deviation. Significant statistical level was chosen as p = 0.05. Our results demonstrate in a cohort from Turkey that rs738409 C > G polymorphism (I148M) of patatin-like phospholipase domain containing 3 gene is significantly able to affect individuals to have NAFLD in unadjusted regression model. Consistent with the previous studies in other populations, our study group showed a significantly higher risk of having NAFLD in unadjusted regression model but not in the adjusted model indicating that non-genetic factors such as age and sex may be responsible for the association. However, independent studies need to validate our findings with a larger group of NAFLD patients, as well as in different ethnic cohorts.

show abstract

The PNPLA3 rs738409 C > G polymorphism is associated with the risk of progression to cirrhosis in NAFLD patients

Cited by 24 publications

References 28 publications

Combining Genetic Variants to Improve Risk Prediction for NAFLD and Its Progression to Cirrhosis: A Proof of Concept Study

Combining Genetic Variants to Improve Risk Prediction for NAFLD and Its Progression to Cirrhosis: A Proof of Concept Study

Association between PNPLA3 rs738409 polymorphism and nonalcoholic fatty liver disease: a systematic review and meta-analysis

The influence of RS738409 I148M polymorphism of patatin-like phospholipase domain containing 3 gene on the susceptibility of non-alcoholic fatty liver disease

Contact Info

Product

Resources

About