Background ATG16L1 rs2241880 (T300A), a single-nucleotide variant, plays a controversial role in the development of Crohn’s disease (CD). Aim This meta-analysis aimed to explore the association between rs2241880 and CD among different subgroups by collecting the largest sample size published so far. Methods We retrieved articles from China National Knowledge Infrastructure, PubMed, Web of Science, and Embase databases, adhered to the PRISMA 2020 guidelines. The correlation between the rs2241880 variant and CD was assessed with a combined effect size of the calculated 95% confidence interval (CI) and odds ratio (OR). Heterogeneity was assessed by the I2 value among genetic models. Publication bias was tested using the Egger test and funnel plot. Results The rs2241880 G allele is positively correlated with the risk of CD worldwide, with an OR of 1.33 (95% CI: 1.29–1.37) for the comparison of G vs. A. This variant is identified as a risk factor for CD progression across all racial subgroups, particularly highlighting an association between Mongolians and CD risk (G vs. A: OR = 1.24, 95% CI: 1.15–1.34). Furthermore, there are statistically significant differences observed across age subgroups, with adults showing an OR of 1.33 (95% CI: 1.29–1.38) and children an OR of 1.27 (95% CI: 1.10–1.47). Gender-wise, the risk remains significant with a male vs. female comparison yielding an OR of 1.33 (95% CI: 1.29–1.37). Additionally, when comparing the overall co-dominant models, GA carriers exhibited a lower risk compared to GG carriers. Specifically, GA vs. AA showed an OR of 1.30 (95% CI: 1.23–1.38), while GG vs. AA revealed a higher risk with an OR of 1.76 (95% CI: 1.65–1.88). Conclusion The ATG16L1 rs2241880 G allele is associated with an increased risk of CD globally, acting as a risk factor across various demographics, including age (both adults and children), gender, and particularly within Mongolian populations. A gene dosage-dependent effect may enhance the strength of this association, as GG carriers of the ATG16L1 rs2241880 G/A allele polymorphism exhibit a higher risk for CD compared to GA carriers.

Population stratified differences between ATG16L1 rs2241880 polymorphism with Crohn's disease risk: a systematic review and meta-analysis

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2025年10月15日

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Yiyuan Gao,
Yuan Zhang,
Peidu Jiang

摘要

Background

ATG16L1 rs2241880 (T300A), a single-nucleotide variant, plays a controversial role in the development of Crohn’s disease (CD).

Aim

This meta-analysis aimed to explore the association between rs2241880 and CD among different subgroups by collecting the largest sample size published so far.

Methods

We retrieved articles from China National Knowledge Infrastructure, PubMed, Web of Science, and Embase databases, adhered to the PRISMA 2020 guidelines. The correlation between the rs2241880 variant and CD was assessed with a combined effect size of the calculated 95% confidence interval (CI) and odds ratio (OR). Heterogeneity was assessed by the I² value among genetic models. Publication bias was tested using the Egger test and funnel plot.

Results

The rs2241880 G allele is positively correlated with the risk of CD worldwide, with an OR of 1.33 (95% CI: 1.29–1.37) for the comparison of G vs. A. This variant is identified as a risk factor for CD progression across all racial subgroups, particularly highlighting an association between Mongolians and CD risk (G vs. A: OR = 1.24, 95% CI: 1.15–1.34). Furthermore, there are statistically significant differences observed across age subgroups, with adults showing an OR of 1.33 (95% CI: 1.29–1.38) and children an OR of 1.27 (95% CI: 1.10–1.47). Gender-wise, the risk remains significant with a male vs. female comparison yielding an OR of 1.33 (95% CI: 1.29–1.37). Additionally, when comparing the overall co-dominant models, GA carriers exhibited a lower risk compared to GG carriers. Specifically, GA vs. AA showed an OR of 1.30 (95% CI: 1.23–1.38), while GG vs. AA revealed a higher risk with an OR of 1.76 (95% CI: 1.65–1.88).

Conclusion

The ATG16L1 rs2241880 G allele is associated with an increased risk of CD globally, acting as a risk factor across various demographics, including age (both adults and children), gender, and particularly within Mongolian populations. A gene dosage-dependent effect may enhance the strength of this association, as GG carriers of the ATG16L1 rs2241880 G/A allele polymorphism exhibit a higher risk for CD compared to GA carriers.