Introduction: Alcohol-induced osteonecrosis of the femoral head (ONFH), a progressive disease, is caused by excessive drinking and genetic factors. Currently, it remains to represent a significant challenge. The association between alcohol-induced ONFH and RAB40C  gene polymorphisms may provide a direction for the mechanism of alcoholic ONFH.
Methods: A total of 201 alcohol-induced ONFH patients and 201 healthy controls were recruited in this case–control study. The polymorphisms of RAB40C  gene were genotyped in blood samples by Agena MassARRAY RS1000. Pearson chi-square test was used to calculate difference in allele frequencies of gene polymorphisms between the cases and controls. Alcohol-induced ONFH risk was estimated using odds ratios (ORs) and 95% confidence intervals (CIs).
Results: In the overall analysis, the allele “G” of rs62030917 was significantly increased alcohol-induced ONFH risk (OR = 1.47, 95% CI = 1.07– 2.02, p = 0.017) in the allele model. In the genetic analysis, rs62030917 also increased the risk of alcohol-induced ONFH in the dominant model (adjusted OR = 1.52, 95% CI=1.02– 2.26, p = 0.039) and the log-additive model (adjusted OR = 1.42, 95% CI=1.05– 1.93, p = 0.025). Age stratification analysis suggested that rs62030917 increased the risk of alcohol-induced ONFH among the individuals younger than 42 years old. Moreover, carriers of AA, GA and GG genotypes in rs2269556 had LDL-C levels that were significantly different (p = 0.047). Among them, carriers of GG genotype had the highest LDL-C levels.
Conclusion: This study revealed rs62030917 in RAB40C  gene might increase the risk of alcohol-induced ONFH, providing a theoretical basis for the mechanism of RAB40C  in alcohol-induced ONFH.
Keywords: alcohol-induced ONFH, RAB40C , single nucleotide polymorphisms