INVESTIGADORES
PIROLA Carlos Jose
artículos
Título:
Meta-analysis of the influence of I148M variant of patatin-like phospholipase domain containing 3 gene (PNPLA3) on susceptibility and histological severity of nonalcoholic fatty liver disease.
Autor/es:
SOOKOIAN S; PIROLA CJ
Revista:
HEPATOLOGY (BALTIMORE, MD.)
Editorial:
JOHN WILEY & SONS INC
Referencias:
Año: 2011 vol. 53 p. 1883 - 1894
ISSN:
0270-9139
Resumen:
Our objective was to estimate the strength of the effect of the I148M (rs738409 C/G) patatin-
like phospholipase domain containing 3 (PNPLA3) variant on nonalcoholic fatty liver
(NAFLD) and disease severity across different populations. We performed a systematic
review by a meta-analysis; literature searches identified 16 studies. Our results showed that
rs738409 exerted a strong influence not only on liver fat accumulation (GG homozygous
showed 73% higher lipid fat content when compared with CC ones, data from 2,937 subjects;
(NAFLD) and disease severity across different populations. We performed a systematic
review by a meta-analysis; literature searches identified 16 studies. Our results showed that
rs738409 exerted a strong influence not only on liver fat accumulation (GG homozygous
showed 73% higher lipid fat content when compared with CC ones, data from 2,937 subjects;
PNPLA3) variant on nonalcoholic fatty liver
(NAFLD) and disease severity across different populations. We performed a systematic
review by a meta-analysis; literature searches identified 16 studies. Our results showed that
rs738409 exerted a strong influence not only on liver fat accumulation (GG homozygous
showed 73% higher lipid fat content when compared with CC ones, data from 2,937 subjects;
P < 1 3 1029), but also on the susceptibility of a more aggressive disease (GG homozygous
had 3.24-fold greater risk of higher necroinflammatory scores and 3.2-fold greater
risk of developing fibrosis when compared with CC homozygous; P < 1 3 1029; data
from 1,739 and 2,251 individuals, respectively). Nonalcoholic steatohepatitis (NASH) was
more frequently observed in GG than CC homozygous (odds ratio [OR] 3.488, 95% confi-
dence interval [CI] 1.859-6.545, random model; P < 2 3 1024; data from 2,124 patients).
Evaluation of the risk associated with heterozygosity for the variant suggests that the additive
genetic model best explains the effect of rs738409 on the susceptibility to develop
NAFLD. Nevertheless, carrying two G alleles does not seem to increase the risk of severe
histological features. Meta-regression showed a negative correlation between male sex and
the effect of rs738409 on liver fat content (slope: 22.45 6 1.04; P < 0.02). The rs738409
GG genotype versus the CC genotype was associated with a 28% increase in serum alanine
aminotransferase levels. Conclusion: By summarizing the amount of evidence, this study
provided unequivocal evidence of rs738409 as a strong modifier of the natural history of
NAFLD in different populations around the world. (HEPATOLOGY 2011;53:1883-1894)
provided unequivocal evidence of rs738409 as a strong modifier of the natural history of
NAFLD in different populations around the world. (HEPATOLOGY 2011;53:1883-1894)
GG genotype versus the CC genotype was associated with a 28% increase in serum alanine
aminotransferase levels. Conclusion: By summarizing the amount of evidence, this study
provided unequivocal evidence of rs738409 as a strong modifier of the natural history of
NAFLD in different populations around the world. (HEPATOLOGY 2011;53:1883-1894)
provided unequivocal evidence of rs738409 as a strong modifier of the natural history of
NAFLD in different populations around the world. (HEPATOLOGY 2011;53:1883-1894)
Evaluation of the risk associated with heterozygosity for the variant suggests that the additive
genetic model best explains the effect of rs738409 on the susceptibility to develop
NAFLD. Nevertheless, carrying two G alleles does not seem to increase the risk of severe
histological features. Meta-regression showed a negative correlation between male sex and
the effect of rs738409 on liver fat content (slope: 22.45 6 1.04; P < 0.02). The rs738409
GG genotype versus the CC genotype was associated with a 28% increase in serum alanine
aminotransferase levels. Conclusion: By summarizing the amount of evidence, this study
provided unequivocal evidence of rs738409 as a strong modifier of the natural history of
NAFLD in different populations around the world. (HEPATOLOGY 2011;53:1883-1894)
provided unequivocal evidence of rs738409 as a strong modifier of the natural history of
NAFLD in different populations around the world. (HEPATOLOGY 2011;53:1883-1894)
GG genotype versus the CC genotype was associated with a 28% increase in serum alanine
aminotransferase levels. Conclusion: By summarizing the amount of evidence, this study
provided unequivocal evidence of rs738409 as a strong modifier of the natural history of
NAFLD in different populations around the world. (HEPATOLOGY 2011;53:1883-1894)
provided unequivocal evidence of rs738409 as a strong modifier of the natural history of
NAFLD in different populations around the world. (HEPATOLOGY 2011;53:1883-1894)
from 1,739 and 2,251 individuals, respectively). Nonalcoholic steatohepatitis (NASH) was
more frequently observed in GG than CC homozygous (odds ratio [OR] 3.488, 95% confi-
dence interval [CI] 1.859-6.545, random model; P < 2 3 1024; data from 2,124 patients).
Evaluation of the risk associated with heterozygosity for the variant suggests that the additive
genetic model best explains the effect of rs738409 on the susceptibility to develop
NAFLD. Nevertheless, carrying two G alleles does not seem to increase the risk of severe
histological features. Meta-regression showed a negative correlation between male sex and
the effect of rs738409 on liver fat content (slope: 22.45 6 1.04; P < 0.02). The rs738409
GG genotype versus the CC genotype was associated with a 28% increase in serum alanine
aminotransferase levels. Conclusion: By summarizing the amount of evidence, this study
provided unequivocal evidence of rs738409 as a strong modifier of the natural history of
NAFLD in different populations around the world. (HEPATOLOGY 2011;53:1883-1894)
provided unequivocal evidence of rs738409 as a strong modifier of the natural history of
NAFLD in different populations around the world. (HEPATOLOGY 2011;53:1883-1894)
GG genotype versus the CC genotype was associated with a 28% increase in serum alanine
aminotransferase levels. Conclusion: By summarizing the amount of evidence, this study
provided unequivocal evidence of rs738409 as a strong modifier of the natural history of
NAFLD in different populations around the world. (HEPATOLOGY 2011;53:1883-1894)
provided unequivocal evidence of rs738409 as a strong modifier of the natural history of
NAFLD in different populations around the world. (HEPATOLOGY 2011;53:1883-1894)
Evaluation of the risk associated with heterozygosity for the variant suggests that the additive
genetic model best explains the effect of rs738409 on the susceptibility to develop
NAFLD. Nevertheless, carrying two G alleles does not seem to increase the risk of severe
histological features. Meta-regression showed a negative correlation between male sex and
the effect of rs738409 on liver fat content (slope: 22.45 6 1.04; P < 0.02). The rs738409
GG genotype versus the CC genotype was associated with a 28% increase in serum alanine
aminotransferase levels. Conclusion: By summarizing the amount of evidence, this study
provided unequivocal evidence of rs738409 as a strong modifier of the natural history of
NAFLD in different populations around the world. (HEPATOLOGY 2011;53:1883-1894)
provided unequivocal evidence of rs738409 as a strong modifier of the natural history of
NAFLD in different populations around the world. (HEPATOLOGY 2011;53:1883-1894)
GG genotype versus the CC genotype was associated with a 28% increase in serum alanine
aminotransferase levels. Conclusion: By summarizing the amount of evidence, this study
provided unequivocal evidence of rs738409 as a strong modifier of the natural history of
NAFLD in different populations around the world. (HEPATOLOGY 2011;53:1883-1894)
provided unequivocal evidence of rs738409 as a strong modifier of the natural history of
NAFLD in different populations around the world. (HEPATOLOGY 2011;53:1883-1894)
had 3.24-fold greater risk of higher necroinflammatory scores and 3.2-fold greater
risk of developing fibrosis when compared with CC homozygous; P < 1 3 1029; data
from 1,739 and 2,251 individuals, respectively). Nonalcoholic steatohepatitis (NASH) was
more frequently observed in GG than CC homozygous (odds ratio [OR] 3.488, 95% confi-
dence interval [CI] 1.859-6.545, random model; P < 2 3 1024; data from 2,124 patients).
Evaluation of the risk associated with heterozygosity for the variant suggests that the additive
genetic model best explains the effect of rs738409 on the susceptibility to develop
NAFLD. Nevertheless, carrying two G alleles does not seem to increase the risk of severe
histological features. Meta-regression showed a negative correlation between male sex and
the effect of rs738409 on liver fat content (slope: 22.45 6 1.04; P < 0.02). The rs738409
GG genotype versus the CC genotype was associated with a 28% increase in serum alanine
aminotransferase levels. Conclusion: By summarizing the amount of evidence, this study
provided unequivocal evidence of rs738409 as a strong modifier of the natural history of
NAFLD in different populations around the world. (HEPATOLOGY 2011;53:1883-1894)
provided unequivocal evidence of rs738409 as a strong modifier of the natural history of
NAFLD in different populations around the world. (HEPATOLOGY 2011;53:1883-1894)
GG genotype versus the CC genotype was associated with a 28% increase in serum alanine
aminotransferase levels. Conclusion: By summarizing the amount of evidence, this study
provided unequivocal evidence of rs738409 as a strong modifier of the natural history of
NAFLD in different populations around the world. (HEPATOLOGY 2011;53:1883-1894)
provided unequivocal evidence of rs738409 as a strong modifier of the natural history of
NAFLD in different populations around the world. (HEPATOLOGY 2011;53:1883-1894)
Evaluation of the risk associated with heterozygosity for the variant suggests that the additive
genetic model best explains the effect of rs738409 on the susceptibility to develop
NAFLD. Nevertheless, carrying two G alleles does not seem to increase the risk of severe
histological features. Meta-regression showed a negative correlation between male sex and
the effect of rs738409 on liver fat content (slope: 22.45 6 1.04; P < 0.02). The rs738409
GG genotype versus the CC genotype was associated with a 28% increase in serum alanine
aminotransferase levels. Conclusion: By summarizing the amount of evidence, this study
provided unequivocal evidence of rs738409 as a strong modifier of the natural history of
NAFLD in different populations around the world. (HEPATOLOGY 2011;53:1883-1894)
provided unequivocal evidence of rs738409 as a strong modifier of the natural history of
NAFLD in different populations around the world. (HEPATOLOGY 2011;53:1883-1894)
GG genotype versus the CC genotype was associated with a 28% increase in serum alanine
aminotransferase levels. Conclusion: By summarizing the amount of evidence, this study
provided unequivocal evidence of rs738409 as a strong modifier of the natural history of
NAFLD in different populations around the world. (HEPATOLOGY 2011;53:1883-1894)
provided unequivocal evidence of rs738409 as a strong modifier of the natural history of
NAFLD in different populations around the world. (HEPATOLOGY 2011;53:1883-1894)
from 1,739 and 2,251 individuals, respectively). Nonalcoholic steatohepatitis (NASH) was
more frequently observed in GG than CC homozygous (odds ratio [OR] 3.488, 95% confi-
dence interval [CI] 1.859-6.545, random model; P < 2 3 1024; data from 2,124 patients).
Evaluation of the risk associated with heterozygosity for the variant suggests that the additive
genetic model best explains the effect of rs738409 on the susceptibility to develop
NAFLD. Nevertheless, carrying two G alleles does not seem to increase the risk of severe
histological features. Meta-regression showed a negative correlation between male sex and
the effect of rs738409 on liver fat content (slope: 22.45 6 1.04; P < 0.02). The rs738409
GG genotype versus the CC genotype was associated with a 28% increase in serum alanine
aminotransferase levels. Conclusion: By summarizing the amount of evidence, this study
provided unequivocal evidence of rs738409 as a strong modifier of the natural history of
NAFLD in different populations around the world. (HEPATOLOGY 2011;53:1883-1894)
provided unequivocal evidence of rs738409 as a strong modifier of the natural history of
NAFLD in different populations around the world. (HEPATOLOGY 2011;53:1883-1894)
GG genotype versus the CC genotype was associated with a 28% increase in serum alanine
aminotransferase levels. Conclusion: By summarizing the amount of evidence, this study
provided unequivocal evidence of rs738409 as a strong modifier of the natural history of
NAFLD in different populations around the world. (HEPATOLOGY 2011;53:1883-1894)
provided unequivocal evidence of rs738409 as a strong modifier of the natural history of
NAFLD in different populations around the world. (HEPATOLOGY 2011;53:1883-1894)
Evaluation of the risk associated with heterozygosity for the variant suggests that the additive
genetic model best explains the effect of rs738409 on the susceptibility to develop
NAFLD. Nevertheless, carrying two G alleles does not seem to increase the risk of severe
histological features. Meta-regression showed a negative correlation between male sex and
the effect of rs738409 on liver fat content (slope: 22.45 6 1.04; P < 0.02). The rs738409
GG genotype versus the CC genotype was associated with a 28% increase in serum alanine
aminotransferase levels. Conclusion: By summarizing the amount of evidence, this study
provided unequivocal evidence of rs738409 as a strong modifier of the natural history of
NAFLD in different populations around the world. (HEPATOLOGY 2011;53:1883-1894)
provided unequivocal evidence of rs738409 as a strong modifier of the natural history of
NAFLD in different populations around the world. (HEPATOLOGY 2011;53:1883-1894)
GG genotype versus the CC genotype was associated with a 28% increase in serum alanine
aminotransferase levels. Conclusion: By summarizing the amount of evidence, this study
provided unequivocal evidence of rs738409 as a strong modifier of the natural history of
NAFLD in different populations around the world. (HEPATOLOGY 2011;53:1883-1894)
provided unequivocal evidence of rs738409 as a strong modifier of the natural history of
NAFLD in different populations around the world. (HEPATOLOGY 2011;53:1883-1894)
< 1 3 1029), but also on the susceptibility of a more aggressive disease (GG homozygous
had 3.24-fold greater risk of higher necroinflammatory scores and 3.2-fold greater
risk of developing fibrosis when compared with CC homozygous; P < 1 3 1029; data
from 1,739 and 2,251 individuals, respectively). Nonalcoholic steatohepatitis (NASH) was
more frequently observed in GG than CC homozygous (odds ratio [OR] 3.488, 95% confi-
dence interval [CI] 1.859-6.545, random model; P < 2 3 1024; data from 2,124 patients).
Evaluation of the risk associated with heterozygosity for the variant suggests that the additive
genetic model best explains the effect of rs738409 on the susceptibility to develop
NAFLD. Nevertheless, carrying two G alleles does not seem to increase the risk of severe
histological features. Meta-regression showed a negative correlation between male sex and
the effect of rs738409 on liver fat content (slope: 22.45 6 1.04; P < 0.02). The rs738409
GG genotype versus the CC genotype was associated with a 28% increase in serum alanine
aminotransferase levels. Conclusion: By summarizing the amount of evidence, this study
provided unequivocal evidence of rs738409 as a strong modifier of the natural history of
NAFLD in different populations around the world. (HEPATOLOGY 2011;53:1883-1894)
provided unequivocal evidence of rs738409 as a strong modifier of the natural history of
NAFLD in different populations around the world. (HEPATOLOGY 2011;53:1883-1894)
GG genotype versus the CC genotype was associated with a 28% increase in serum alanine
aminotransferase levels. Conclusion: By summarizing the amount of evidence, this study
provided unequivocal evidence of rs738409 as a strong modifier of the natural history of
NAFLD in different populations around the world. (HEPATOLOGY 2011;53:1883-1894)
provided unequivocal evidence of rs738409 as a strong modifier of the natural history of
NAFLD in different populations around the world. (H