An eQTL variant of ALDH1A2 is associated with Kashin-Beck disease in Chinese population

Introduction The aims of the study were to investigate the relationship between aldehyde dehydrogenase 1 family member A2 ( ALDH1A2 ) and Kashin-Beck disease (KBD), explore the effects of the rs3204689 polymorphism and methylation status on the expression levels of ALDH1A2, and further clarify the pathogenesis of KBD. Materials and methods The genotype of ALDH1A2 rs3204689 was detected by PCR–RFLP in 103 KBD patients and 109 healthy controls in the whole blood. The mRNA level of ALDH1A2 was measured by qRT-PCR, and the protein expression was detected using IHC staining and Western blotting. The MSP-PCR was used to identify the ALDH1A2 methylation level. Results There were significant differences in G/G, G/C, and C/C frequencies of ALDH1A2 rs3204689 between the KBD and control groups ( χ 2 = 7.113, P = 0.029); the minor allele G of ALDH1A2 was associated with the risk of KBD ( χ 2 = 5.984, P = 0.014). The mRNA and protein levels of ALDH1A2 were increased in the whole blood and cartilage of KBD patients compared with the controls ( P = 0.049, P < 0.0001, P = 0.019). Meanwhile, a statistically significant difference was observed between G/G, G/C and C/C genotype on mRNA expression ( P = 0.039). The methylation level of the ALDH1A2 gene promoter region showed no significant difference between the KBD and control groups ( χ 2 = 0.317, P = 0.573). Conclusion Our case–control study indicates that the common variant rs3204689 near ALDH1A2 is associated with KBD in Chinese population. The risk allele G of rs3204689 is statistically linked to the high expression of ALDH1A2, which is up-regulated in the cartilage and whole blood of KBD patients. Our findings suggest a potential role of ALDH1A2 in the pathogenesis of KBD.