Association of peroxisome proliferator-activated receptor gamma polymorphisms with inflammatory bowel disease in a Hungarian cohort

Póliska, Szilárd; Penyige, András; Lakatos, Péter L.; Papp, Mária; Palatka, Károly; Lakatos, László; Molnár, Tamás; Nagy, László

doi:10.1002/ibd.21798

Cited by 14 publications

(14 citation statements)

References 51 publications

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“…3 studies recruited healthy blood donors as controls [10], [20], [21]. One study recruited healthy medical staff as controls [11].…”

Section: Resultsmentioning

confidence: 99%

“…The association between the PPARγ Pro12Ala polymorphism and UC in the European Caucasian population was investigated in 2 studies with 598 UC cases and 1271 controls [10], [21]. There was no significant association between the Pro12Ala polymorphism and UC in the European Caucasian population (Pro vs Ala: OR = 1.047, 95%CI = 0.858–1.277, P = 0.651, Bon = 1.000; ProPro vs ProAla: OR = 1.157, 95%CI = 0.917–1.459, P = 0.219, Bon = 1.000; ProPro vs AlaAla: OR = 0.680, 95%CI = 0.346–1.335, P = 0.263, Bon = 1.000; ProAla vs AlaAla: OR = 0.586, 95%CI = 0.293–1.173, P = 0.131, Bon = 0.917; Pro homozygotes vs Ala positives: OR = 1.109, 95%CI = 0.886–1.388, P = 0.365, Bon = 1.000; Pro positives vs Ala homozygotes: OR = 0.653, 95%CI = 0.334–1.280, P = 0.215, Bon = 1.000; heterozygotes vs all homozygotes: OR = 0.854, 95%CI = 0.678–1.077, P = 0.183, Bon = 1.000).…”

Section: Resultsmentioning

confidence: 99%

“…One case-control study conducted in Japan indicated that the Pro12Ala mutation was more frequently found in UC patients [9]. Another study showed a significant association between this mutation and the development of CD [10]. However, a research conducted in China and Holland failed to confirm the association between the Pro12Ala polymorphism and IBD [11].…”

Section: Introductionmentioning

confidence: 99%

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Association between the Pro12Ala Polymorphism of Peroxisome Proliferator-Activated Receptor Gamma 2 and Inflammatory Bowel Disease: A Meta-Analysis

et al. 2012

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BackgroundPeroxisome proliferator-activated receptor gamma (PPARγ), a nuclear receptor, has been implicated playing a role in the development of inflammatory bowel disease (IBD). However, previous studies evaluating the association between the PPARγ2 Pro12Ala polymorphism and IBD are inconsistent. We performed a meta-analysis to determine whether the PPARγ2 Pro12Ala mutation was associated with the presence of IBD.Methods and FindingsElectronic databases were searched for case-control studies evaluating the association between the Pro12Ala mutation and the presence of IBD. Effects were summarized with the methods recommended by the Cochrane Collaboration. A total of 7 studies including 1002 ulcerative colitis (UC) cases, 1090 Crohǹs disease (CD) cases and 1983 controls were involved in this meta-analysis. In the overall analysis, no significant association of this polymorphism with UC or CD was found. In the subgroup analyses in different populations, AlaAla genotype seemed to protect the European Caucasian population against the development of CD (Pro vs Ala: OR = 1.135, 95%CI = 0.951–1.354, P = 0.162, Bon = 1.000; ProPro vs ProAla: OR = 1.042, 95%CI = 0.852–1.273, P = 0.690, Bon = 1.000; ProPro vs AlaAla: OR = 2.379, 95%CI = 1.110–5.100, P = 0.026, Bon = 0.156; ProAla vs AlaAla: OR = 2.315, 95%CI = 1.064–5.037, P = 0.034, Bon = 0.204; Pro homozygotes vs Ala positives: OR = 1.094, 95%CI = 0.899–1.330, P = 0.371, Bon = 1.000; Pro positives vs Ala homozygotes: OR = 2.360, 95%CI = 1.103–5.053, P = 0.027, Bon = 0.162; heterozygotes vs all homozygotes: OR = 0.976, 95%CI = 0.799–1.192, P = 0.809, Bon = 1.000). There was no significant association of this polymorphism with UC or CD in the East Asian population and the Turkish population.ConclusionAlaAla genotype may be a protective factor in the European Caucasian population against the development of CD in a recessive way.

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“…3 studies recruited healthy blood donors as controls [10], [20], [21]. One study recruited healthy medical staff as controls [11].…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Association between the Pro12Ala Polymorphism of Peroxisome Proliferator-Activated Receptor Gamma 2 and Inflammatory Bowel Disease: A Meta-Analysis

et al. 2012

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“…15, 16, 17 The PPAR γ agonists inhibit Th17 cell differentiation in lung myeloid dendritic cells and promote Treg cell differentiation in the white adipose tissue of mice. 18, 19, 20, 21 Meanwhile, various pentacyclic triterpenes were reported to activate PPAR γ . 22, 23 These findings suggested that the triterpenes in C. asiatica might restore the Th17/Treg balance through the PPAR γ pathway.…”

mentioning

confidence: 99%

Madecassic acid, the contributor to the anti-colitis effect of madecassoside, enhances the shift of Th17 toward Treg cells via the PPARγ/AMPK/ACC1 pathway

Wang

Wei

et al. 2017

Cell Death Dis

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The imbalance between Th17 and Treg cells substantially contributes to the intestinal immune disturbance and subsequent tissue injury in ulcerative colitis. The triterpenoid-rich fraction of Centella asiatica was able to ameliorate dextran sulfate sodium-induced colitis in mice. Here we explored its active ingredient and underlying mechanism with a focus on restoring the Th17/Treg balance. The four main triterpenoids occurring in C. asiatica were shown to attenuate colitis in mice by oral administration. The most effective ingredient madecassoside lost anti-colitis effect when applied topically in the colon, and madecassic acid was recognized to be the active form of madecassoside. Oral administration of madecassic acid decreased the percentage of Th17 cells and downregulated the expression of RORγt, IL-17A, IL-17F, IL-21 and IL-22 and increased the percentage of Treg cells and the expression of Foxp3 and IL-10 in the colons of mice with colitis, but it did not affect Th1 and Th2 cells. Under Th17-polarizing conditions, madecassic acid downregulated ACC1 expression and enhanced the shift of Th17 cells toward Treg cells, but it did not affect the differentiation of Treg cells under Treg-polarizing conditions. Both compound C and AMPK siRNA inhibited the madecassic acid-mediated downregulation of ACC1 expression and shift of Th17 cells to Treg cells under Th17-polarizing conditions. GW9662, T0070907 and PPARγ siRNA blocked the effect of madecassic acid on AMPK activation, ACC1 expression and shift of Th17 cells to Treg cells. Furthermore, madecassic acid was identified as a PPARγ agonist, as it promoted PPARγ transactivation. The correlation between activation of PPARγ and AMPK, downregulation of ACC1 expression, restoration of Th17/Treg balance and attenuation of colitis by madecassic acid was validated in mice with DSS-induced colitis. In conclusion, madecassic acid was the active form of madecassoside in ameliorating colitis by restoring the Th17/Treg balance via regulating the PPARγ/AMPK/ACC1 pathway.

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“…PPAR-γ2 is a sub-type of PPAR that is only expressed in adipose tissue (14). The Pro 12 Ala single nucleotide (rs1801282) polymorphism is a C/G mutation that may be associated with the modifications of the risk of a number of diseases (15)(16)(17)(18).…”

Section: Introductionmentioning

confidence: 99%

Peroxisome proliferator-activated receptor γ2 Pro12Ala (rs1801282) polymorphism and breast cancer susceptibility: A meta-analysis

Mao

Guo

Gao

et al. 2013

Molecular Medicine Reports

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Abstract. Several studies have investigated the correlation between the peroxisome proliferator-activated receptor γ2 (PPAR-γ2) Pro 12 Ala (rs1801282) polymorphism and the risk of breast cancer, with inconsistent results. For this reason, a meta-analysis was conducted to identify the potential correlation after pooling data from eligible case-control studies. Search strategies were conducted in PubMed, EMBASE and the COCHRANE Library in English and from VIP, CNKI and Sinomed in Chinese (all the papers were published before November 11, 2012) using appropriate terms. A total of 2,279 cases and 2,360 controls from four related case-control studies were included in this meta-analysis. According to the three eligible populations, the odds ratios (ORs) and 95% confidence intervals (CIs) on the risk of breast cancer for the CG versus CC and GG versus CC genotypes and the G versus C allele were 0.84 and 0.72-0.98, 0.92 and 0.32-2.61, and 0.98 and 0.84-1.13, respectively. The OR and 95% CI for CG+GG versus CC from the four study populations were 0.85 and 0.73-0.98, respectively. This meta-analysis supported the fact that the G allele of PPAR-γ2 Pro 12 Ala (rs1801282) modestly affects the risk of breast cancer. Nevertheless, further studies are required to enrich the evidence of this correlation.

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Association of peroxisome proliferator-activated receptor gamma polymorphisms with inflammatory bowel disease in a Hungarian cohort

Abstract: In the present study we demonstrated a significant association between PPARγ polymorphisms and the development of CD and UC at single loci level and also in haplotype combinations.

Cited by 14 publications

References 51 publications

Association between the Pro12Ala Polymorphism of Peroxisome Proliferator-Activated Receptor Gamma 2 and Inflammatory Bowel Disease: A Meta-Analysis

Association between the Pro12Ala Polymorphism of Peroxisome Proliferator-Activated Receptor Gamma 2 and Inflammatory Bowel Disease: A Meta-Analysis

Madecassic acid, the contributor to the anti-colitis effect of madecassoside, enhances the shift of Th17 toward Treg cells via the PPARγ/AMPK/ACC1 pathway

Peroxisome proliferator-activated receptor γ2 Pro12Ala (rs1801282) polymorphism and breast cancer susceptibility: A meta-analysis

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