No evidence for a causal link between Helicobacter pylori infection and nonalcoholic fatty liver disease: A bidirectional Mendelian randomization study

Abstract

Although clinical studies have shown the possible relationship between Helicobacter pylori (H. pylori) infection and the development of nonalcoholic fatty liver disease (NAFLD), their causal relationship is still unknown. This bidirectional Mendelian randomization (MR) study aimed to investigate the causal link between H. pylori infection and NAFLD. Two previously reported genetic variants SNPs rs10004195 and rs368433 were used as the instrumental variables (IVs) of H. pylori infection. The genetic variants of NAFLD were extracted from the largest genome-wide association study (GWAS) summary data with 1,483 cases and 17,781 controls. The exposure and outcome data were obtained from the publicly available GWAS dataset. Then, a bidirectional MR was carried out to evaluate the causal relationship between H. pylori infection and NAFLD. In addition, the GWAS data were also collected to explore the causal relationship between H. pylori infection and relevant clinical traits of NAFLD, including triglycerides, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), fasting blood glucose (FBG), and body mass index (BMI). Genetically predicted H. pylori infection showed no association with NAFLD both in FinnGen GWAS (OR, 1.048; 95% CI, 0.778–1.411; value of p = 0.759) and the GWAS conducted by Anstee (OR, 0.775; 95% CI, 0.475–1.265; value of p = 0.308). An inverse MR showed no causal effect of NAFLD on H. pylori infection (OR,0.978;95% CI, 0.909–1.052; value of p = 0.543). No significant associations were observed between H. pylori infection and the levels of triglycerides, LDL-C, HDL-C, or FBG, while H. pylori infection was associated with an increase in BMI. These results indicated that there was no genetic evidence for a causal link between H. pylori and NAFLD, suggesting that the eradication or prevention of H. pylori infection might not benefit NAFLD and vice versa.

Causal Effect ofHelicobacter PyloriInfection on Coronary Heart Disease is mediated by Body Mass Index: A Mendelian Randomization Study

“…Based on previous studies, SNP rs10004195 (T > A) and SNP rs368433 (T > C) are strongly related to H. pylori infection, 24 We therefore used the two SNPs as IVs of H. pylori infection to predict the relationship between H. pylori infection and the diagnosis of CHD, MI, and angina pectoris. 23 Genetically predicted H. pylori infection showed no association with the occurrence of CHD (IEU) [odds ratio (OR), 0.991; 95% confidence interval (CI), 0.904–1.078; p -value = 0.842], CHD (Finn) (OR, 1.049; 95% CI, 0.980–1.118; p -value = 0.178), angina pectoris (OR, 1.105; 95% CI, 1.019–1.191; p -value = 0.023), or MI (OR, 0.993; 95% CI, 0.896–1.091; p -value = 0.889) under the IVW method.…”

“…Based on previous studies, SNP rs10004195 (T > A) and SNP rs368433 (T > C) are strongly related to H. pylori infection, 24 We therefore used the two SNPs as IVs of H.…”

Interactions between Helicobacter pylori infection and host metabolic homeostasis: A comprehensive review

“…Furthermore, a glycosylated hemoglobin level of 10.8% was identified as a threshold indicating an inverse relationship between glycosylated hemoglobin levels and the risk of H. pylori infection 18 . However, Mendelian randomization analysis conducted by FinnGen and Anstee, adjusting for SNP variants rs10004195 and rs368433, did not support bidirectional causal effects between NAFLD and H. pylori infection 19 …”

“…18 However, Mendelian randomization analysis conducted by FinnGen and Anstee, adjusting for SNP variants rs10004195 and rs368433, did not support bidirectional causal effects between NAFLD and H. pylori infection. 19 Regarding histological severity in NAFLD patients with H. pylori infection, a small-scale study with 64 eligible participants demonstrated that the presence of H. pylori significantly increased the prevalence of hepatic steatosis, inflammation, fibrosis, nonalcoholic steatohepatitis (NASH) (β = 3.27; p = 0.002), and severe NASH (β = 2.37; p = 0.018). 20 However, due to the limited sample size and single-center study design, further research is necessary to strengthen these conclusions.…”

Helicobacter pylori infection exacerbates nonalcoholic fatty liver disease through lipid metabolic pathways: a transcriptomic study.

“…However, other studies have found no association between H. pylori infection and NAFLD. A Mendelian randomization study by Liu et al revealed no causal link between H. pylori infection and NAFLD and no signi cant association between H. pylori infection and TGs, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), or FBG levels [19]. Interestingly, a cross-sectional study by Kang et al indicated that Cag A status may be critical to in uencing the relationship between the two, and there was no association between the Cag A positive H. pylori group and NAFLD (OR: 1.05; 95% CI: 0.81-1.37), and in multivariate analysis, the Cag A negative (Cag A-) H. pylori group was signi cantly associated with NAFLD (OR: 1.30; 95% CI: 1.01-1.67) [20].…”