Limits...
Lack of association between peroxisome proliferator-activated receptors alpha and gamma2 polymorphisms and progressive liver damage in patients with non-alcoholic fatty liver disease: a case control study.

Dongiovanni P, Rametta R, Fracanzani AL, Benedan L, Borroni V, Maggioni P, Maggioni M, Fargion S, Valenti L - BMC Gastroenterol (2010)

Bottom Line: The frequency of the evaluated SNPs did not differ between patients and 346 healthy controls.The PPARα 162Val and PPARγ2 12Ala alleles were not associated with the severity of steatosis, necroinflammation, or fibrosis.Because of the limited power of the present sample, larger studies are needed to exclude a minor effect of the PPARγ2 12Ala allele on necroinflammation/fibrosis in NAFLD.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Internal Medicine, Metabolic Liver Diseases Research Center, Università degli Studi di Milano, Fondazione Ospedale Policlinico Ca' Granda IRCCS, Milano, Italy.

ABSTRACT

Background: Peroxisome proliferator-activated receptors (PPARs) play key roles in the pathogenesis of nonalcoholic fatty liver disease (NAFLD).

Aim: to assess the effect of functional single nucleotide polymorphisms (SNPs) of PPARα and PPARγ2, previously associated with insulin resistance and dyslipidemia, on liver damage in NAFLD, whose progression is influenced by metabolic abnormalities and inherited factors.

Methods: The Leu162Val PPARα and Pro12Ala PPARγ2 SNPs were evaluated by restriction analysis. We considered 202 Italian patients with biopsy-proven NAFLD.

Results: The frequency of the evaluated SNPs did not differ between patients and 346 healthy controls. The presence of the PPARα 162Val allele (prevalence 57%), but not of the PPARγ2 12Ala allele (prevalence 18%), was associated with higher insulin resistance (HOMA-IR index 4.71 ± 3.8 vs. 3.58 ± 2.7, p = 0.026), but not with hyperglycemia. The PPARα 162Val and PPARγ2 12Ala alleles were not associated with the severity of steatosis, necroinflammation, or fibrosis.

Conclusions: The presence of the PPARα 162Val allele was associated with insulin resistance, but not with liver damage in NAFLD. Because of the limited power of the present sample, larger studies are needed to exclude a minor effect of the PPARγ2 12Ala allele on necroinflammation/fibrosis in NAFLD.

Show MeSH

Related in: MedlinePlus

Prevalence of severe histological activity (NASH activity score (NAS) > 5) in 202 biopsied patients with non-alcoholic fatty liver disease (NAFLD), subdivided according to the presence or absence of the PPARα 162Val and PPARγ2 12Ala SNPs.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2944335&req=5

Figure 2: Prevalence of severe histological activity (NASH activity score (NAS) > 5) in 202 biopsied patients with non-alcoholic fatty liver disease (NAFLD), subdivided according to the presence or absence of the PPARα 162Val and PPARγ2 12Ala SNPs.

Mentions: The effect of inherited factors on the severity of liver disease, evaluated as presence of severe histological activity (NAS > 5) and of severe fibrosis (Kleiner > 1), is shown in figure 2 and 3 respectively. No significant effect of the PPARα 162Val and PPARγ2 12Ala alleles was observed on liver damage. The prevalence of NAS > 5 was similar between patients positive and negative for the PPARα 162Val allele (6% vs. 8%; p = ns). In patients positive for the PPARγ2 12Ala allele, the prevalence of NAS > 5 was lower compared to that observed in negative patients (3% vs. 8%; p = ns). Although the PPARγ2 12Ala allele was associated with a lower prevalence of severe histological activity, the sample size is too small to cross the statistical significance threshold. The prevalence of fibrosis > 1 was 22% in patients positive for PPARα 162Val and 14% in those negative for this allele (p = ns). Also for the PPARγ2 SNP, the prevalence of fibrosis > 1 was similar in patients carrying the 12Ala allele compared to the negative ones (19% vs. 18%; p = ns).


Lack of association between peroxisome proliferator-activated receptors alpha and gamma2 polymorphisms and progressive liver damage in patients with non-alcoholic fatty liver disease: a case control study.

Dongiovanni P, Rametta R, Fracanzani AL, Benedan L, Borroni V, Maggioni P, Maggioni M, Fargion S, Valenti L - BMC Gastroenterol (2010)

Prevalence of severe histological activity (NASH activity score (NAS) > 5) in 202 biopsied patients with non-alcoholic fatty liver disease (NAFLD), subdivided according to the presence or absence of the PPARα 162Val and PPARγ2 12Ala SNPs.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2944335&req=5

Figure 2: Prevalence of severe histological activity (NASH activity score (NAS) > 5) in 202 biopsied patients with non-alcoholic fatty liver disease (NAFLD), subdivided according to the presence or absence of the PPARα 162Val and PPARγ2 12Ala SNPs.
Mentions: The effect of inherited factors on the severity of liver disease, evaluated as presence of severe histological activity (NAS > 5) and of severe fibrosis (Kleiner > 1), is shown in figure 2 and 3 respectively. No significant effect of the PPARα 162Val and PPARγ2 12Ala alleles was observed on liver damage. The prevalence of NAS > 5 was similar between patients positive and negative for the PPARα 162Val allele (6% vs. 8%; p = ns). In patients positive for the PPARγ2 12Ala allele, the prevalence of NAS > 5 was lower compared to that observed in negative patients (3% vs. 8%; p = ns). Although the PPARγ2 12Ala allele was associated with a lower prevalence of severe histological activity, the sample size is too small to cross the statistical significance threshold. The prevalence of fibrosis > 1 was 22% in patients positive for PPARα 162Val and 14% in those negative for this allele (p = ns). Also for the PPARγ2 SNP, the prevalence of fibrosis > 1 was similar in patients carrying the 12Ala allele compared to the negative ones (19% vs. 18%; p = ns).

Bottom Line: The frequency of the evaluated SNPs did not differ between patients and 346 healthy controls.The PPARα 162Val and PPARγ2 12Ala alleles were not associated with the severity of steatosis, necroinflammation, or fibrosis.Because of the limited power of the present sample, larger studies are needed to exclude a minor effect of the PPARγ2 12Ala allele on necroinflammation/fibrosis in NAFLD.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Internal Medicine, Metabolic Liver Diseases Research Center, Università degli Studi di Milano, Fondazione Ospedale Policlinico Ca' Granda IRCCS, Milano, Italy.

ABSTRACT

Background: Peroxisome proliferator-activated receptors (PPARs) play key roles in the pathogenesis of nonalcoholic fatty liver disease (NAFLD).

Aim: to assess the effect of functional single nucleotide polymorphisms (SNPs) of PPARα and PPARγ2, previously associated with insulin resistance and dyslipidemia, on liver damage in NAFLD, whose progression is influenced by metabolic abnormalities and inherited factors.

Methods: The Leu162Val PPARα and Pro12Ala PPARγ2 SNPs were evaluated by restriction analysis. We considered 202 Italian patients with biopsy-proven NAFLD.

Results: The frequency of the evaluated SNPs did not differ between patients and 346 healthy controls. The presence of the PPARα 162Val allele (prevalence 57%), but not of the PPARγ2 12Ala allele (prevalence 18%), was associated with higher insulin resistance (HOMA-IR index 4.71 ± 3.8 vs. 3.58 ± 2.7, p = 0.026), but not with hyperglycemia. The PPARα 162Val and PPARγ2 12Ala alleles were not associated with the severity of steatosis, necroinflammation, or fibrosis.

Conclusions: The presence of the PPARα 162Val allele was associated with insulin resistance, but not with liver damage in NAFLD. Because of the limited power of the present sample, larger studies are needed to exclude a minor effect of the PPARγ2 12Ala allele on necroinflammation/fibrosis in NAFLD.

Show MeSH
Related in: MedlinePlus