Genotypic and functional roles of IL-1B and IL-1RN on the risk of gastroesophageal reflux disease

the presence of IL-1B-511*T/IL-1RN*1 (T1) haplotype may protect against the disease

Dipti Chourasia, B R Achyut, Shweta Tripathi, Balraj Mittal, Rama D Mittal, Uday C Ghoshal

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

OBJECTIVES: We aimed at evaluating the role of interleukin-1B (IL-1B) and IL-1RN polymorphisms, which may modulate the gastric mucosal expression of IL-1beta, thus altering acid secretion, which influences the severity of gastroesphageal reflux disease (GERD).

METHODS: In a prospective study, 144 patients with GERD (diagnosed by at least two of these criteria: Carlsson-Dent score of 6, endoscopic evidence of GERD, histopathological evidence of esophagitis, percentage time esophageal pH <4 for >5% on 24-h pH monitoring, and response to omeprazole 20 mg/day) and 368 healthy controls were genotyped for IL-1B-511 C/T and IL-1RN VNTR polymorphism (by PCR-restriction fragment length polymorphism (RFLP) and PCR, respectively). Gastric mucosal IL-1beta levels (picogram/milligram of biopsy sample) were measured (using enzyme-linked immunosorbent assay (ELISA)) in 71 patients. Helicobacter pylori diagnosis was conducted using anti-H. pylori immunoglobulin G (IgG) ELISA.

RESULTS: Patients (41.1+/-13.3 years old, 96 (66.7%) men) were comparable with healthy controls (43.4+/-11.8 years old, 238 (64.7%) men) with respect to age and gender. The IL-1B-511 CC genotype and C allele were associated with higher risk of GERD than the TT genotype (P=0.01, odds ratio (OR)=2.0, 95% confidence interval (CI)=1.12-3.57) and the T allele (P=0.04, OR=1.3, 95% CI=1.0-1.7), respectively. TT and C noncarriers had more IL-1beta than CT (33.2 (2.6-161.3) vs. 16.7 (2.8-121.9), P=0.04) and C carriers (33.2 (2.6-161.3) vs. 15.16 (1.5-121.9), P=0.04), respectively. IL-1RN "1,2" and "2 carriers" had higher risk (P<0.001, OR=2.0, 95% CI=1.31-3.1; P=0.01, OR=1.6, 95% CI=1.1-2.4, respectively). "2,2" Had lower IL-1beta levels than both "1,1" and "1,2" (9.2 (1.5-70.7) vs. 26.8 (5.7-161.3), P=0.006; 9.2 (1.5-70.7) vs. 24.4 (2.6-78.0), P=0.02). However, "2 carriers" tended to have lower IL-1beta levels than "2 noncarriers" (21.7 (1.5-78.0) vs. 26.8 (5.7-161.3), P=0.09). The IL-1B-511*T/IL-1RN*1 ("T1") haplotype showed lower risk (P=0.05, OR=0.7, 95% CI=0.5-1.0). "T1" had higher IL-1beta levels than both "T1 carriers" and "T1 noncarriers" (43.5 (18.2-161.3) vs. 23.9 (2.6-121.9), P=0.02; 43.5 (18.2-161.3) vs. 10.9 (1.5-82.6), P=0.06, respectively). The presence of H. pylori infection was associated with the stronger risk of the IL-1B-511*CC genotype. The "T1" haplotype was strongly protective against GERD among patients with H. pylori infection.

CONCLUSIONS: The T1 haplotype was associated with the reduced risk of GERD, particularly among patients with H. pylori infection, probably because of higher gastric mucosal IL-1beta levels.

Original languageEnglish (US)
Pages (from-to)2704-13
Number of pages10
JournalAmerican Journal of Gastroenterology
Volume104
Issue number11
DOIs
StatePublished - Nov 2009

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Interleukins
Gastroesophageal Reflux
Interleukin-1
Haplotypes
Helicobacter pylori
Odds Ratio
Confidence Intervals
Helicobacter Infections
Stomach
Genotype
Enzyme-Linked Immunosorbent Assay
Alleles
Polymerase Chain Reaction
Omeprazole
Esophagitis
Restriction Fragment Length Polymorphisms
Immunoglobulin G
Prospective Studies
Biopsy
Acids

Keywords

  • Adult
  • Biopsy, Needle
  • Case-Control Studies
  • Confidence Intervals
  • Enzyme-Linked Immunosorbent Assay
  • Esophagoscopy
  • Female
  • Follow-Up Studies
  • Gastroesophageal Reflux
  • Gene Expression Regulation
  • Genetic Predisposition to Disease
  • Genotype
  • Haplotypes
  • Helicobacter Infections
  • Helicobacter pylori
  • Humans
  • Immunohistochemistry
  • Incidence
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1beta
  • Male
  • Middle Aged
  • Minisatellite Repeats
  • Odds Ratio
  • Polymerase Chain Reaction
  • Polymorphism, Genetic
  • Probability
  • Prospective Studies
  • Severity of Illness Index
  • Statistics, Nonparametric
  • Comparative Study
  • Journal Article
  • Research Support, Non-U.S. Gov't

Cite this

Genotypic and functional roles of IL-1B and IL-1RN on the risk of gastroesophageal reflux disease : the presence of IL-1B-511*T/IL-1RN*1 (T1) haplotype may protect against the disease. / Chourasia, Dipti; Achyut, B R; Tripathi, Shweta; Mittal, Balraj; Mittal, Rama D; Ghoshal, Uday C.

In: American Journal of Gastroenterology, Vol. 104, No. 11, 11.2009, p. 2704-13.

Research output: Contribution to journalArticle

Chourasia, Dipti ; Achyut, B R ; Tripathi, Shweta ; Mittal, Balraj ; Mittal, Rama D ; Ghoshal, Uday C. / Genotypic and functional roles of IL-1B and IL-1RN on the risk of gastroesophageal reflux disease : the presence of IL-1B-511*T/IL-1RN*1 (T1) haplotype may protect against the disease. In: American Journal of Gastroenterology. 2009 ; Vol. 104, No. 11. pp. 2704-13.
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abstract = "OBJECTIVES: We aimed at evaluating the role of interleukin-1B (IL-1B) and IL-1RN polymorphisms, which may modulate the gastric mucosal expression of IL-1beta, thus altering acid secretion, which influences the severity of gastroesphageal reflux disease (GERD).METHODS: In a prospective study, 144 patients with GERD (diagnosed by at least two of these criteria: Carlsson-Dent score of 6, endoscopic evidence of GERD, histopathological evidence of esophagitis, percentage time esophageal pH <4 for >5{\%} on 24-h pH monitoring, and response to omeprazole 20 mg/day) and 368 healthy controls were genotyped for IL-1B-511 C/T and IL-1RN VNTR polymorphism (by PCR-restriction fragment length polymorphism (RFLP) and PCR, respectively). Gastric mucosal IL-1beta levels (picogram/milligram of biopsy sample) were measured (using enzyme-linked immunosorbent assay (ELISA)) in 71 patients. Helicobacter pylori diagnosis was conducted using anti-H. pylori immunoglobulin G (IgG) ELISA.RESULTS: Patients (41.1+/-13.3 years old, 96 (66.7{\%}) men) were comparable with healthy controls (43.4+/-11.8 years old, 238 (64.7{\%}) men) with respect to age and gender. The IL-1B-511 CC genotype and C allele were associated with higher risk of GERD than the TT genotype (P=0.01, odds ratio (OR)=2.0, 95{\%} confidence interval (CI)=1.12-3.57) and the T allele (P=0.04, OR=1.3, 95{\%} CI=1.0-1.7), respectively. TT and C noncarriers had more IL-1beta than CT (33.2 (2.6-161.3) vs. 16.7 (2.8-121.9), P=0.04) and C carriers (33.2 (2.6-161.3) vs. 15.16 (1.5-121.9), P=0.04), respectively. IL-1RN {"}1,2{"} and {"}2 carriers{"} had higher risk (P<0.001, OR=2.0, 95{\%} CI=1.31-3.1; P=0.01, OR=1.6, 95{\%} CI=1.1-2.4, respectively). {"}2,2{"} Had lower IL-1beta levels than both {"}1,1{"} and {"}1,2{"} (9.2 (1.5-70.7) vs. 26.8 (5.7-161.3), P=0.006; 9.2 (1.5-70.7) vs. 24.4 (2.6-78.0), P=0.02). However, {"}2 carriers{"} tended to have lower IL-1beta levels than {"}2 noncarriers{"} (21.7 (1.5-78.0) vs. 26.8 (5.7-161.3), P=0.09). The IL-1B-511*T/IL-1RN*1 ({"}T1{"}) haplotype showed lower risk (P=0.05, OR=0.7, 95{\%} CI=0.5-1.0). {"}T1{"} had higher IL-1beta levels than both {"}T1 carriers{"} and {"}T1 noncarriers{"} (43.5 (18.2-161.3) vs. 23.9 (2.6-121.9), P=0.02; 43.5 (18.2-161.3) vs. 10.9 (1.5-82.6), P=0.06, respectively). The presence of H. pylori infection was associated with the stronger risk of the IL-1B-511*CC genotype. The {"}T1{"} haplotype was strongly protective against GERD among patients with H. pylori infection.CONCLUSIONS: The T1 haplotype was associated with the reduced risk of GERD, particularly among patients with H. pylori infection, probably because of higher gastric mucosal IL-1beta levels.",
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author = "Dipti Chourasia and Achyut, {B R} and Shweta Tripathi and Balraj Mittal and Mittal, {Rama D} and Ghoshal, {Uday C}",
year = "2009",
month = "11",
doi = "10.1038/ajg.2009.382",
language = "English (US)",
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pages = "2704--13",
journal = "American Journal of Gastroenterology",
issn = "0002-9270",
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TY - JOUR

T1 - Genotypic and functional roles of IL-1B and IL-1RN on the risk of gastroesophageal reflux disease

T2 - the presence of IL-1B-511*T/IL-1RN*1 (T1) haplotype may protect against the disease

AU - Chourasia, Dipti

AU - Achyut, B R

AU - Tripathi, Shweta

AU - Mittal, Balraj

AU - Mittal, Rama D

AU - Ghoshal, Uday C

PY - 2009/11

Y1 - 2009/11

N2 - OBJECTIVES: We aimed at evaluating the role of interleukin-1B (IL-1B) and IL-1RN polymorphisms, which may modulate the gastric mucosal expression of IL-1beta, thus altering acid secretion, which influences the severity of gastroesphageal reflux disease (GERD).METHODS: In a prospective study, 144 patients with GERD (diagnosed by at least two of these criteria: Carlsson-Dent score of 6, endoscopic evidence of GERD, histopathological evidence of esophagitis, percentage time esophageal pH <4 for >5% on 24-h pH monitoring, and response to omeprazole 20 mg/day) and 368 healthy controls were genotyped for IL-1B-511 C/T and IL-1RN VNTR polymorphism (by PCR-restriction fragment length polymorphism (RFLP) and PCR, respectively). Gastric mucosal IL-1beta levels (picogram/milligram of biopsy sample) were measured (using enzyme-linked immunosorbent assay (ELISA)) in 71 patients. Helicobacter pylori diagnosis was conducted using anti-H. pylori immunoglobulin G (IgG) ELISA.RESULTS: Patients (41.1+/-13.3 years old, 96 (66.7%) men) were comparable with healthy controls (43.4+/-11.8 years old, 238 (64.7%) men) with respect to age and gender. The IL-1B-511 CC genotype and C allele were associated with higher risk of GERD than the TT genotype (P=0.01, odds ratio (OR)=2.0, 95% confidence interval (CI)=1.12-3.57) and the T allele (P=0.04, OR=1.3, 95% CI=1.0-1.7), respectively. TT and C noncarriers had more IL-1beta than CT (33.2 (2.6-161.3) vs. 16.7 (2.8-121.9), P=0.04) and C carriers (33.2 (2.6-161.3) vs. 15.16 (1.5-121.9), P=0.04), respectively. IL-1RN "1,2" and "2 carriers" had higher risk (P<0.001, OR=2.0, 95% CI=1.31-3.1; P=0.01, OR=1.6, 95% CI=1.1-2.4, respectively). "2,2" Had lower IL-1beta levels than both "1,1" and "1,2" (9.2 (1.5-70.7) vs. 26.8 (5.7-161.3), P=0.006; 9.2 (1.5-70.7) vs. 24.4 (2.6-78.0), P=0.02). However, "2 carriers" tended to have lower IL-1beta levels than "2 noncarriers" (21.7 (1.5-78.0) vs. 26.8 (5.7-161.3), P=0.09). The IL-1B-511*T/IL-1RN*1 ("T1") haplotype showed lower risk (P=0.05, OR=0.7, 95% CI=0.5-1.0). "T1" had higher IL-1beta levels than both "T1 carriers" and "T1 noncarriers" (43.5 (18.2-161.3) vs. 23.9 (2.6-121.9), P=0.02; 43.5 (18.2-161.3) vs. 10.9 (1.5-82.6), P=0.06, respectively). The presence of H. pylori infection was associated with the stronger risk of the IL-1B-511*CC genotype. The "T1" haplotype was strongly protective against GERD among patients with H. pylori infection.CONCLUSIONS: The T1 haplotype was associated with the reduced risk of GERD, particularly among patients with H. pylori infection, probably because of higher gastric mucosal IL-1beta levels.

AB - OBJECTIVES: We aimed at evaluating the role of interleukin-1B (IL-1B) and IL-1RN polymorphisms, which may modulate the gastric mucosal expression of IL-1beta, thus altering acid secretion, which influences the severity of gastroesphageal reflux disease (GERD).METHODS: In a prospective study, 144 patients with GERD (diagnosed by at least two of these criteria: Carlsson-Dent score of 6, endoscopic evidence of GERD, histopathological evidence of esophagitis, percentage time esophageal pH <4 for >5% on 24-h pH monitoring, and response to omeprazole 20 mg/day) and 368 healthy controls were genotyped for IL-1B-511 C/T and IL-1RN VNTR polymorphism (by PCR-restriction fragment length polymorphism (RFLP) and PCR, respectively). Gastric mucosal IL-1beta levels (picogram/milligram of biopsy sample) were measured (using enzyme-linked immunosorbent assay (ELISA)) in 71 patients. Helicobacter pylori diagnosis was conducted using anti-H. pylori immunoglobulin G (IgG) ELISA.RESULTS: Patients (41.1+/-13.3 years old, 96 (66.7%) men) were comparable with healthy controls (43.4+/-11.8 years old, 238 (64.7%) men) with respect to age and gender. The IL-1B-511 CC genotype and C allele were associated with higher risk of GERD than the TT genotype (P=0.01, odds ratio (OR)=2.0, 95% confidence interval (CI)=1.12-3.57) and the T allele (P=0.04, OR=1.3, 95% CI=1.0-1.7), respectively. TT and C noncarriers had more IL-1beta than CT (33.2 (2.6-161.3) vs. 16.7 (2.8-121.9), P=0.04) and C carriers (33.2 (2.6-161.3) vs. 15.16 (1.5-121.9), P=0.04), respectively. IL-1RN "1,2" and "2 carriers" had higher risk (P<0.001, OR=2.0, 95% CI=1.31-3.1; P=0.01, OR=1.6, 95% CI=1.1-2.4, respectively). "2,2" Had lower IL-1beta levels than both "1,1" and "1,2" (9.2 (1.5-70.7) vs. 26.8 (5.7-161.3), P=0.006; 9.2 (1.5-70.7) vs. 24.4 (2.6-78.0), P=0.02). However, "2 carriers" tended to have lower IL-1beta levels than "2 noncarriers" (21.7 (1.5-78.0) vs. 26.8 (5.7-161.3), P=0.09). The IL-1B-511*T/IL-1RN*1 ("T1") haplotype showed lower risk (P=0.05, OR=0.7, 95% CI=0.5-1.0). "T1" had higher IL-1beta levels than both "T1 carriers" and "T1 noncarriers" (43.5 (18.2-161.3) vs. 23.9 (2.6-121.9), P=0.02; 43.5 (18.2-161.3) vs. 10.9 (1.5-82.6), P=0.06, respectively). The presence of H. pylori infection was associated with the stronger risk of the IL-1B-511*CC genotype. The "T1" haplotype was strongly protective against GERD among patients with H. pylori infection.CONCLUSIONS: The T1 haplotype was associated with the reduced risk of GERD, particularly among patients with H. pylori infection, probably because of higher gastric mucosal IL-1beta levels.

KW - Adult

KW - Biopsy, Needle

KW - Case-Control Studies

KW - Confidence Intervals

KW - Enzyme-Linked Immunosorbent Assay

KW - Esophagoscopy

KW - Female

KW - Follow-Up Studies

KW - Gastroesophageal Reflux

KW - Gene Expression Regulation

KW - Genetic Predisposition to Disease

KW - Genotype

KW - Haplotypes

KW - Helicobacter Infections

KW - Helicobacter pylori

KW - Humans

KW - Immunohistochemistry

KW - Incidence

KW - Interleukin 1 Receptor Antagonist Protein

KW - Interleukin-1beta

KW - Male

KW - Middle Aged

KW - Minisatellite Repeats

KW - Odds Ratio

KW - Polymerase Chain Reaction

KW - Polymorphism, Genetic

KW - Probability

KW - Prospective Studies

KW - Severity of Illness Index

KW - Statistics, Nonparametric

KW - Comparative Study

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1038/ajg.2009.382

DO - 10.1038/ajg.2009.382

M3 - Article

VL - 104

SP - 2704

EP - 2713

JO - American Journal of Gastroenterology

JF - American Journal of Gastroenterology

SN - 0002-9270

IS - 11

ER -