Gene–gene interaction and association of Wnt/Β-catenin signalling pathway gene polymorphisms with ankylosing spondylitis susceptibility in the Chinese Han population

Abstract

Objectives: To explore the genetic interaction between Wnt/β-catenin signalling pathway genes and ankylosing spondylitis (AS) in the Chinese population.

Methods: Six single-nucleotide polymorphisms (SNPs) in DKK1, LRP5, LRP6, and SOST genes were genotyped in 673 AS patients and 687 healthy controls by using SNPs can Technic. Single marker genetic association analysis was performed. Haplotypes were constructed after linkage disequilibrium analysis; additive, multiplicative, and higher-order interactions were analysed.

Results: The DKK1 gene rs1569198 polymorphism was significantly associated with AS susceptibility in females (χ² = 4.55, p = .03), but the association disappeared after Bonferroni correction. Moreover, a haplotype (T-G) in the DKK1 gene showed a protective role in AS susceptibility in females (p = .04). Significant additive interactions were observed between DKK1: rs1896368 and LRP5: rs3736228, relative excess risk due to interaction (RERI) = 0.40, 95% CI = 0.08 – 0.71; attributable proportion due to interaction (AP) = 51%, 95% CI = 0.07 – 0.94, DKK1: rs1569198 and LRP5: rs3736228 (RERI = 0.49, 95% CI = 0.12 – 0.86; AP = 49%, 95% CI = 0.17 – 0.82), LRP5: rs3736228 and SOST: rs4792909 (RERI = 0.33, 95% CI = 0.002 – 0.65; AP = 41%, 95% CI = 0.01 – 0.81) in the dominant model.

Conclusions: Our research implies a potential gene–gene interaction, thus revealing the importance of the Wnt/β-catenin signalling pathway for understanding the genetic architecture of AS.

Keywords:

• Ankylosing spondylitis
• polymorphism
• interaction
• gene
• Wnt/β-catenin

Acknowledgments

This paper was supported by the First Affiliated Hospital of Anhui Medical University. The authors thank all the participants and staffs who made this study possible.

Compliance with ethical standards

This study conformed to the Declaration of Helsinki, and the design of the work was reviewed and approved by the Ethics Committee of Anhui Medical University. All participants agreed to participate in this study and provided their written informed consents.

Author contributions statements

FMP had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study design: RL and XZ. Study conduct: RL, XZ, GMJ, YBM, JJY, WM, RFH, MYC, YPY and XXH. Data collection: RL, XZ, GMJ, YBM, JJY, WM, RFH, MYC, YPY and XXH. Data analysis: RL, XZ, GMJ, GXP, YFZ and FMP. Data interpretation: RL and FMP. Drafting manuscript: RL. Revising manuscript content: SQX, JHX, ZWS and FMP.

Disclosure of interest

The authors report no conflict of interest.

Additional information

Funding

This study was supported by grants from the National Natural Science Foundation of China [30771849, 30972530, 81273169, 81573218, 81773514] and was supported by grants from the Academic and Technical Leaders Foundation of Anhui province [2017D140].