Exploring the Relationship between ACE Gene Variants and Systemic Lupus Erythematosus Susceptibility in the Hainan Population through Genetic Association Analysis

Background: The purpose of this study was to determine the association between single nucleotide polymorphisms (SNPs) at the rs4331, rs4341, and rs4351 loci of the angiotensin- converting enzyme (ACE) gene and genetic susceptibility to systemic lupus erythematosus (SLE) in the Hainan population. Methods: This study involved a total of 428 participants, with 214 individuals diagnosed with SLE and an equal number of healthy controls. The SNaPshot sequencing technique was used to determine the base sequences at the ACE gene rs4331, rs4341, and rs4351 loci in the study subjects. Logistic regression was employed to compare the frequency distribution of genotypes and allele frequencies at each locus between the case group and the control group. HaploView 4.2 software was used to analyze the relationship between haplotypes at each locus and genetic susceptibility to SLE. Results: The GG genotype and G allele frequency at the rs4341 locus were higher in the case group compared to the control group. In the rs4341 recessive model, carriers of the GG genotype were more likely to develop SLE compared to carriers of the CG+CC genotype (OR = 1.889, 95% CI: 1.195-2.988, P = 0.006). In the rs4351 overdominant model, carriers of the AC genotype had an increased risk of developing SLE compared to carriers of the AA+CC genotype (OR = 1.514, 95% CI: 1.033-2.219, P = 0.033). The rs4341 and rs4351 loci exhibited linkage disequilibrium, and the CA haplotype (OR = 0.630, 95% CI: 0.481-0.826, P = 0.001) was a protective factor against SLE. The GA haplotype (OR = 2.849, 95% CI: 1.901-4.270, P < 0.01) and the CC haplotype (OR = 2.309, 95% CI: 1.210-4.405, P = 0.009) were risk factors for genetic susceptibility to SLE in the Hainan population. Conclusion: The rs4341 locus of the ACE gene is associated with genetic susceptibility to SLE in the Hainan population.