Association of TLR-9 polymorphisms with the development of gastroduodenal ulcer: A hospital-based study in a Chinese cohort

Abstract

Helicobacter pylori infections have been one of the major factors associated with gastroduodenal ulcer. Toll-like receptors (TLRs) of human recognize mycobacterium-induced immune response and protect subjects from disease pathogenesis. Variants in TLR genes are believed to influence immune responses to H. pylori and clinical severity. TLR-9 polymorphisms have been associated with susceptibility to gastroduodenal ulcer in different populations. In this study, we investigate the role of common TLR-9 variants in susceptibility/resistance to the development of gastroduodenal ulcer in a Chinese cohort. The present hospital-based case–control study enrolled 580 patients with abdominal discomfort, and based on endoscopic investigation, the patients were categorized into (1) gastric ulcer (n = 154), (2) duodenal ulcer (n = 70), (3) gastric and duodenal ulcers (n = 25), (4) gastritis (n = 195), and (5) healthy stomach (n = 136). A total of 520 healthy controls from similar geographical areas were enrolled as controls. TLR-9 (C-1237T, C-1486T, and G+2848A) polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Plasma levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β in both healthy controls and patients were quantified by enzyme-linked immunosorbent assay (ELISA). Furthermore, messenger RNA (mRNA) expressions of TNF-α, IL-6, and IL-1β in biopsy tissues were quantified by real-time polymerase chain reaction (RT-PCR). The prevalence of TLR-9+2848 heterozygotes (CT) was significantly higher in gastroduodenal ulcer patients compared to healthy controls. Sub-categorization of patients revealed higher prevalence of heterozygotes of TLR-9 C+2848T and C-1486T polymorphisms in patients with gastric ulcer (GU), duodenal ulcer (DU), and those with both gastric and duodenal ulcers (GDU) when compared to controls. Patients displayed higher plasma cytokine levels than healthy controls. TLR-9 polymorphisms (C+2848T and C-1486T) correlated with altered cytokine expression in biopsy tissues and their plasma levels. In conclusion, TLR-9 (C+2848T and C-1486T) polymorphisms are associated with gastroduodenal ulcer and correlated with altered cytokine levels.