Medical and Dental Consultantsí Association of Nigeria
Home - About us - Editorial board - Search - Ahead of print - Current issue - Archives - Submit article - Instructions - Subscribe - Advertise - Contacts - Login 
  Users Online: 1985   Home Print this page Email this page Small font sizeDefault font sizeIncrease font size
 

  Table of Contents 
REVIEW ARTICLE
Year : 2019  |  Volume : 22  |  Issue : 2  |  Page : 149-153

Association between IL-10 polymorphisms rs1800896 and rs1800871 and risk of acute pancreatitis in Chinese Han population: An update systemic review and meta-analysis


Department of Surgery, The Second Affiliated Hospital of Zhejiang University, Hangzhou, P.R. China

Date of Acceptance19-Oct-2018
Date of Web Publication7-Feb-2019

Correspondence Address:
Dr. Y Zhu
Department of Surgery, The Second Affiliated Hospital of Zhejiang University, No. 88 Jiefang Road, Hangzhou
P.R. China
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/njcp.njcp_57_18

Rights and Permissions
   Abstract 


The association between interleukin-10 (IL-10) promoter region (1082 A/G (rs1800896), 819 C/T (rs1800871)) polymorphisms, and acute pancreatitis (AP) is inconclusive in Chinese Han population. In this study, six eligible studies extracted from the databases of PubMed, Web of Science, and Cochrane Library were evaluated. The results revealed a significant association between 1082 A/G (rs1800896) polymorphism and AP risk in all these five models (AG/AA: OR = 1.19, 95% Cl = 1.02–1.40, P = 0.03; GG/AA: OR = 1.80, 95% Cl = 1.38–2.23, P = 0.01; AG+GG/AA: OR = 1.29, 95% Cl = 1.11–1.50, P = 0.01; GG/AG+AA: OR = 1.62, 95% Cl = 1.27–2.08, P = 0.01; G/A: OR = 1.29, 95% Cl = 1.15–1.45, P = 0.01). In contrast, no statistically significant association was found in all these five models for 819 C/T (rs1800871) polymorphism. In summary, IL-10 polymorphism 1082 A/G (rs1800896) could increase the risk of AP in Chinese Han population.

Keywords: Acute pancreatitis, Chinese Han population, IL-10 polymorphism


How to cite this article:
Dong L, Zhu Y. Association between IL-10 polymorphisms rs1800896 and rs1800871 and risk of acute pancreatitis in Chinese Han population: An update systemic review and meta-analysis. Niger J Clin Pract 2019;22:149-53

How to cite this URL:
Dong L, Zhu Y. Association between IL-10 polymorphisms rs1800896 and rs1800871 and risk of acute pancreatitis in Chinese Han population: An update systemic review and meta-analysis. Niger J Clin Pract [serial online] 2019 [cited 2019 May 24];22:149-53. Available from: http://www.njcponline.com/text.asp?2019/22/2/149/251798




   Introduction Top


Acute pancreatitis (AP) is a severe inflammatory condition of the pancreas that is mainly caused by gallstone or alcohol consumption.[1],[2] The typical symptoms of AP including abdominal pain, nausea, and vomiting are usually mild in a majority of patients. However, severe AP can lead to systemic organ dysfunction, and the mortality of the disease is up to 20%. To date, the etiology of AP is not completely understood.[3] The fact that not all patients with exposure to similar factors develop AP indicates that genetic factors play an important role in the initiation and development of the disease, such as interleukin-1 gene, heme oxygenase-1 gene, Toll-like receptor gene, tumor necrosis factor alpha gene, and heat-shock protein 70-2 gene.[4],[5],[6],[7]

Interleukin (IL) is a member of the inflammatory cytokine families and participates in the inflammatory response. Previous studies reported that enhanced secretion of IL-1b, IL-6, IL-8, and IL-10 could promote the pathological development of AP and serum levels of IL could be regulated at the transcriptional level.[8],[9],[10] Some polymorphisms in the IL promoter region could control gene transcription and its secretion. Recent evidences have shown that the IL-10 is associated with many inflammation-related diseases,[11],[12] and high concentration of IL-10 in serum is important in promoting the pathological process of AP.[13] Two important polymorphisms in the IL-10 promoter region (1082 A/G (rs1800896), 819 C/T (rs1800871)) were associated with IL-10 gene transcription and its secretion.[14],[15] Therefore, many studies focused on the associations between these two polymorphisms, and the risk of AP and the results were inconclusive. Some researchers found that the rs1800896 and rs1800871 were not associated with the risk of AP in British subjects.[16] However, studies focused on the Chinese patients demonstrated that these two polymorphisms could contribute to AP progression in the Chinese Han population.[17],[18] In recent years, many new studies focused on the association between IL-10 polymorphisms and the risk of AP in Chinese Han population were reported, and no systemic reviews were carried out to summarize the new results.

In this study, we collected all published case-control studies focused on the relationship between AP and IL-10 polymorphism rs1800896 and rs1800871 in Chinese subjects. A meta-analysis was carried out and our aim was to clarify the controversial results.


   Materials and Methods Top


Publication search and data extraction

Studies published in English (from their inception to December 2016) were mainly identified by conducting a systematic search in PubMed, Web of Science, and Cochrane Library databases using the following terms: “IL-10,” “1082 A/G (rs1800896),” “819 C/T (rs1800871),” and “polymorphism.” Reference lists from relevant articles were also examined to find additional publications. Data were extracted independently by two authors using standard forms. The collected data included author name, publication year, country, study design, genotyping method, and genotype distributions. All the included studies met the following criteria: (1) case-control study focused on Chinese Han population, (2) evaluation of the association between IL-10 promoter region (1082 A/G (rs1800896), 819 C/T (rs1800871)) polymorphism, and AP risks, (3) including details of genotype frequency in cases and controls and the frequency was tested by Hardy-Weinberg equilibrium (HWE). Studies were excluded when they were: (1) not case-control study, (2) review, comment, or editorial articles, (3) insufficient data, and (4) repetitive studies. Evaluation of evidence strength was carried out according to the modified Newcastle–Ottawa Scale [Supplementary Table 1].[19]



Statistical analysis

Revman 5.3 (Cochrane Collaboration, Oxford, UK) and STATA 14.0 software (StataCorp, CollegeStation, TX, USA) was used for meta-analysis. Study heterogeneity between studies was assessed using the I2 statistic. Dichotomous variables were quoted as odds ratios (ORs) with 95% confidence intervals (CI). The random-effects model was used when I2> 50%. Otherwise, calculations were performed using the fixed-effects model.[20],[21] We used the codominant model (AG/AA, GG/AA, or CT/CC, TT/CC), dominant model (AG+GG/AA or CT+TT/CC), recessive model (GG/AG+AA or TT/CC+CT), and allele model (G/A or T/C) to evaluate the association between polymorphism and AP risk. Sensitivity analysis and publication bias were also performed.[22],[23] P < 0.05 was considered statistically significant.


   Results Top


Characteristics of the studies

Study flow diagram is shown in [Figure 1]. Eight studies of IL-10 promoter region (1082 A/G (rs1800896), 819 C/T (rs1800871)) polymorphism, and AP risks were found in a primary literature search in PubMed, Web of Science, and Cochrane Library databases. After reviewing each publication, two articles were found inappropriate in the current meta-analysis because they focused on British and Spanish populations. Six studies with 1403 cases and 1384 controls shown in [Table 1] were identified appropriate for the current meta-analysis.[17],[24],[25],[26],[27],[28] The genotype distribution of the control population was in agreement with Hardy–Weinberg equilibrium in all six studies [Table 2].
Figure 1: Study flow diagram

Click here to view
Table 1: Characteristics of studies included in this meta-analysis

Click here to view
Table 2: Genotype distribution and HWE for rs1800896 and rs1800871 polymorphism included in this mea-analysis

Click here to view


Quantitative synthesis

We analyzed the association between IL-10 promoter region (1082 A/G (rs1800896), 819 C/T (rs1800871)) polymorphism, and AP risk within five genetic models as mentioned in the Methods section. The quantitative synthesis results are presented in [Table 3]. Interestingly, the pooled results revealed a significant association between 1082 A/G (rs1800896) polymorphism and AP risk in all these five models (AG/AA: OR = 1.19, 95% Cl = 1.02–1.40, P = 0.03; GG/AA: OR = 1.80, 95% Cl = 1.38–2.23, P = 0.01; AG+GG/AA: OR = 1.29, 95% Cl = 1.11–1.50, P = 0.01; GG/AG+AA: OR = 1.62, 95% Cl = 1.27–2.08, P = 0.01; G/A: OR = 1.29, 95% Cl = 1.15–1.45, P = 0.01). In contrast, no statistically significant association was found in all these five models (CT/CC: OR = 1.14, 95% Cl = 0.94–1.36, P = 0.14; TT/CC: OR = 1.14, 95% Cl = 0.91–1.43, P = 0.25; CT+TT/CC: OR = 1.14, 95% Cl = 0.97–1.35, P = 0.11; TT/CT+CC: OR = 1.07, 95% Cl = 0.87–1.31, P = 0.55; T/C: OR = 1.09, 95% Cl = 0.97–1.22, P = 0.15) for 819 C/T (rs1800871) polymorphism.
Table 3: Pooled ORs and 95% CIs of the overall meta-analysis for codominant model, dominant model, recessive model, and allele model for rs1800896 and rs1800871 polymorphism

Click here to view


Publication bias

The funnel plot was performed to estimate the publication bias. The shape of the funnel plots was symmetrical, suggesting that there was no evidence of publication bias for the IL-10 promoter region (1082 A/G (rs1800896), 819 C/T (rs1800871)) polymorphism [Figure 2]. Begg's test showed no evidence of publication bias (P = 0.851).
Figure 2: Funnel plots for assessing publication bias in the meta-analysis

Click here to view


Sensitivity analysis

To assess the stability of the results, sensitivity analysis was performed. The sensitivity analysis did not detect any individual study, which affected the results using the exclusion method step by step [Figure 3].
Figure 3: Sensitive analysis of studies in the meta-analysis

Click here to view



   Discussion Top


The IL-10 gene plays an important role in regulating immunity response. Previous studies have reported that the IL-10 polymorphism (1082 A/G (rs1800896), 819 C/T (rs1800871) might be involved in the development of AP although the results were inconclusive.[17],[24],[25],[26],[27],[28] In this study, we conducted a systemic meta-analysis to determine the possible association between these two SNPs and the risk of AP. Our results revealed a significant association between 1082 A/G (rs1800896) polymorphism and AP risk in all these five models. In contrast, no statistically significant association was found in all these five models for 819 C/T (rs1800871) polymorphism.

Previous studies reported that IL-10 1082 A/G (rs1800896) polymorphism did not increase the risk of AP in Caucasians.[18],[29] However, this polymorphism could increase the risk of AP in Chinese Han population according to our results. These contrasting findings could be explained by different genetic and environmental factors such as gallstone, alcohol consumption, and lipid level in the blood. A stratified analysis between IL-10 1082 A/G (rs1800896) polymorphism and AP risk based on demographic and lifestyle characteristics showed significant interaction between IL-10 1082A/G (rs1800896) polymorphism and gender, age, family history, body mass index, tobacco smoking, and alcohol drinking in the susceptibility to AP.[27] In addition, some researchers reported that a significant difference was only found in the distribution of IL-10 1082A/G (rs1800896) polymorphism between septic shock patients and nonseptic shock patients.[18] The researchers also focused on the relationship between IL-10 1082 A/G (rs1800896) polymorphism and chronic pancreatitis and found that this polymorphism did not play a dominant role in this disease.[30],[31] In addition, more studies were required to investigate the possible biophysical mechanisms of IL-10 1082 A/G (rs1800896) polymorphism in coordination with other mutations.

Limitations in our analysis should also be considered. First, many other clinical factors such as age, sex, or other mixed mutations in each study might lead to bias and had not been considered in our study. Second, we restricted our search to studies published in English. Third, more subgroup analysis should have been carried out, but no details could be extracted from the original articles. For example, the definition of AP was inconsistent. This disease could be divided to the mild type and severe type, and the pathogenesis of these two subgroups were completely different.

In conclusion, we suggest that IL-10 1082 A/G (rs1800896) polymorphism could contribute to the pathogenesis of AP, and IL-10 819 C/T (rs1800871) polymorphism does not correlate with the increased risk of this disease in Chinese Han population and further investigations are needed to support our findings.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Dufour MC, Adamson MD. The epidemiology of alcohol-induced pancreatitis. Pancreas 2003;27:286-90.  Back to cited text no. 1
    
2.
Venneman NG, Renooij W, Rehfeld JF, VanBerge-Henegouwen GP, Go PM, Broeders IA, et al. Small gallstones, preserved gallbladder motility, and fast crystallization are associated with pancreatitis. Hepatology 2005;41:738-46.  Back to cited text no. 2
    
3.
Frossard JL, Morel P, Pastor CM. Why clinical trials might succeed in acute pancreatitis when they failed in septic shock. JOP 2003;4:11-6.  Back to cited text no. 3
    
4.
Ozhan G, Yanar HT, Ertekin C, Alpertunga B. Polymorphisms in tumour necrosis factor alpha (TNFalpha) gene in patients with acute pancreatitis. Mediators Inflamm 2010;2010:482950.  Back to cited text no. 4
    
5.
Bishehsari F, Sharma A, Stello K, Toth C, O'Connell MR, Evans AC, et al. TNF-alpha gene (TNFA) variants increase risk for multi-organ dysfunction syndrome (MODS) in acute pancreatitis. Pancreatology 2012;12:113-8.  Back to cited text no. 5
    
6.
Srivastava P, Shafiq N, Bhasin DK, Rana SS, Pandhi P, Behera A, et al. Differential expression of heat shock protein (HSP) 70-2 gene polymorphism in benign and malignant pancreatic disorders and its relationship with disease severity and complications. JOP 2012;13:414-9.  Back to cited text no. 6
    
7.
Gulla A, Evans BJ, Navenot JM, Pundzius J, Barauskas G, Gulbinas A, et al. Heme oxygenase-1 gene promoter polymorphism is associated with the development of necrotizing acute pancreatitis. Pancreas 2014;43:1271-6.  Back to cited text no. 7
    
8.
Tang B, Chen YK, Luo WJ, Fu J, Sun JM. Association between interleukin-10 -1082A/G, -819C/T and -592C/A polymorphisms with deep venous thrombosis. Hum Immunol 2014;75:203-7.  Back to cited text no. 8
    
9.
Ying B, Shi Y, Pan X, Song X, Huang Z, Niu Q, et al. Association of polymorphisms in the human IL-10 and IL-18 genes with rheumatoid arthritis. Mol Biol Rep 2011;38:379-85.  Back to cited text no. 9
    
10.
Kang JM, Kim N, Lee DH, Park JH, Lee MK, Kim JS, et al. The effects of genetic polymorphisms of IL-6, IL-8, and IL-10 on Helicobacter pylori-induced gastroduodenal diseases in Korea. J Clin Gastroenterol 2009;43:420-8.  Back to cited text no. 10
    
11.
de Beaux AC, Goldie AS, Ross JA, Carter DC, Fearon KC. Serum concentrations of inflammatory mediators related to organ failure in patients with acute pancreatitis. Br J Surg 1996;83:349-53.  Back to cited text no. 11
    
12.
Berney T, Gasche Y, Robert J, Jenny A, Mensi N, Grau G, et al. Serum profiles of interleukin-6, interleukin-8, and interleukin-10 in patients with severe and mild acute pancreatitis. Pancreas 1999;18:371-7.  Back to cited text no. 12
    
13.
Chen CC, Wang SS, Lee FY, Chang FY, Lee SD. Proinflammatory cytokines in early assessment of the prognosis of acute pancreatitis. Am J Gastroenterol 1999;94:213-8.  Back to cited text no. 13
    
14.
Eskdale J, Gallagher G, Verweij CL, Keijsers V, Westendorp RG, Huizinga TW. Interleukin 10 secretion in relation to human IL-10 locus haplotypes. Proc Natl Acad Sci U S A 1998;95:9465-70.  Back to cited text no. 14
    
15.
Kilpinen S, Huhtala H, Hurme M. The combination of the interleukin-1alpha (IL-1alpha-889) genotype and the interleukin-10 (IL-10 ATA) haplotype is associated with increased interleukin-10 (IL-10) plasma levels in healthy individuals. Eur Cytokine Netw 2002;13:66-71.  Back to cited text no. 15
    
16.
Sargen K, Demaine AG, Kingsnorth AN. Cytokine gene polymorphisms in acute pancreatitis. JOP 2000;1:24-35.  Back to cited text no. 16
    
17.
Jiang BZ, Tang L, Xue H, Liu DP. Role of IL-10 gene polymorphisms in the development of acute pancreatitis. Genet Mol Res 2016;15. doi: 10.4238/gmr. 1502774.  Back to cited text no. 17
    
18.
Zhang DL, Zheng HM, Yu BJ, Jiang ZW, Li JS. Association of polymorphisms of IL and CD14 genes with acute severe pancreatitis and septic shock. World J Gastroenterol 2005;11:4409-13.  Back to cited text no. 18
    
19.
Zhao L, Roffey DM and Chen S. Association Between the Estrogen Receptor Beta (ESR2) Rs1256120 Single Nucleotide Polymorphism and Adolescent Idiopathic Scoliosis: A Systematic Review and Meta-Analysis. Spine (Phila Pa 1976) 2017;42:871-8.  Back to cited text no. 19
    
20.
Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997;315:629-34.  Back to cited text no. 20
    
21.
Lau J, Ioannidis JP, Schmid CH. Quantitative synthesis in systematic reviews. Ann Intern Med 1997;127:820-6.  Back to cited text no. 21
    
22.
Wang X, Lu X, Fang Y, Chen H, Deng X, Peng C, et al. Association between mir34b/c polymorphism rs4938723 and cancer risk: A meta-analysis of 11 studies including 6169 cases and 6337 controls. Med Sci Monit 2014;20:1977-82.  Back to cited text no. 22
    
23.
Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics 1994;50:1088-101.  Back to cited text no. 23
    
24.
Zhang DL, Zheng HM, Yu BJ, Jiang ZW, Li JS. Association of polymorphisms of IL and CD14 genes with acute severe pancreatitis and septic shock. World J Gastroenterol 2005;11:4409-13.  Back to cited text no. 24
    
25.
Li D, Li J, Wang L, Zhang Q. Association between IL-1beta, IL-8, and IL-10 polymorphisms and risk of acute pancreatitis. Genet Mol Res 2015;14:6635-41.  Back to cited text no. 25
    
26.
Jia HL, Sun PL, Lu CQ. Investigation of the association between interleukin-10 polymorphisms and risk of acute pancreatitis in a Chinese population. Genet Mol Res 2015;14:15876-81.  Back to cited text no. 26
    
27.
Cai F, Cui N, Ma H, Wang X, Qiao G, Liu D. Interleukin-10 -1082A/G polymorphism is associated with the development of acute pancreatitis in a Chinese population. Int J Clin Exp Pathol 2015;8:15170-6.  Back to cited text no. 27
    
28.
Bao XB, Ma Z, Gu JB, Wang XQ, Li HG, Wang WY. IL-8 -251T/A polymorphism is associated with susceptibility to acute pancreatitis. Genet Mol Res 2015;14:1508-14.  Back to cited text no. 28
    
29.
de-Madaria E, Martinez J, Sempere L, Lozano B, Sanchez-Paya J, Uceda F, et al. Cytokine genotypes in acute pancreatitis: Association with etiology, severity, and cytokine levels in blood. Pancreas 2008;37:295-301.  Back to cited text no. 29
    
30.
Schneider A, Barmada MM, Slivka A, Martin JA, Whitcomb DC. Analysis of tumor necrosis factor-alpha, transforming growth factor-beta 1, interleukin-10, and interferon-gamma polymorphisms in patients with alcoholic chronic pancreatitis. Alcohol 2004;32:19-24.  Back to cited text no. 30
    
31.
Schneider A, Barmada MM, Slivka A, Martin JA, Whitcomb DC. Transforming growth factor-beta1, interleukin-10 and interferon-gamma cytokine polymorphisms in patients with hereditary, familial and sporadic chronic pancreatitis. Pancreatology 2004;4:490-4.  Back to cited text no. 31
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

Top
  
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
    Abstract
   Introduction
    Materials and Me...
   Results
   Discussion
    References
    Article Figures
    Article Tables

 Article Access Statistics
    Viewed506    
    Printed25    
    Emailed0    
    PDF Downloaded175    
    Comments [Add]    

Recommend this journal