Association of APOA5 rs2075291 and CIDEB rs2144492 Polymorphisms with Hypertriglyceridemia in Individuals with Traditional Chinese Medicine Dampness Syndrome: A Case-Control Study

Na Liu¹Hongli Zeng¹Xiangsheng Cai¹Shuo Yang¹Xinyan Chen²Guli Jiang¹Jiamin Yuan²Jianxiong Cai^2*Hui Zhou^1*

• ¹Guangzhou Eleventh People's Hospital, Guangzhou, China
• ²The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China

Purpose：To investigate the association between polymorphisms of the APOA5 rs2075291 and CIDEB rs2144492 loci and hypertriglyceridemia (HTG) in a population with Traditional Chinese Medicine (TCM) dampness syndrome. Methods：A case-control study was conducted, enrolling 100 HTG patients and 100 age-matched controls with normal triglyceride levels from the physical examination cohort at Guangzhou Eleventh People’s Hospital (January–December 2023). Peripheral blood samples were collected to analyze APOA5 rs2075291 and CIDEB rs2144492 polymorphisms using PCR and sequencing. Lipid profiles were measured via an automated biochemical analyzer. Statistical analyses (chi-square tests, correlation analysis, and logistic regression) evaluated associations  among gene polymorphisms, dampness syndrome, and HTG. Results：The observation group showed significant differences in genotype frequencies of APOA5 rs2075291 (OR=2.916, 95% CI:1.160-7.334, χ²p=0.019) and CIDEB rs2144492 (OR=1.688, 95% CI:0.886-3.141, χ²p=0.042) versus the control group. Significant intergroup differences were also observed in allele frequencies of APOA5 rs2075291 (OR=2.727, 95% CI:1.113-6.682, χ²p=0.023) and CIDEB rs2144492 (OR=1.837, 95% CI:1.040-3.244, χ²p=0.034). Stratified by dampness syndrome status, in the dampness syndrome subgroup, the HTG group had a higher frequency of CIDEB rs2144492 TG/TT genotypes than controls, though the difference was not significant (OR=2.065, 95% CI:0.816–5.226, χ² p=0.146). No significant difference in gene frequency was observed after FDR correction (p=0.043, FDR threshold=0.042). APOA5 rs2075291 showed no significant genotype/allele frequency differences (p>0.05). In the non-dampness subgroup, FDR correction (p ≤ 0.033) revealed no significant differences in APOA5 rs2075291 genotype (OR=4.083, 95% CI:0.977-17.063, χ²p=0.041) or allele frequencies (p=0.05), nor in CIDEB rs2144492 genotypes/allele frequencies (p>0.05). Triglyceride levels did not differ significantly between dampness/non-dampness groups across genotypes (p>0.05). Multivariate logistic regression identified male gender, higher BMI, dampness syndrome, and APOA5 rs2075291 genotype as independent risk factors for HTG (p<0.05), while CIDEB rs2144492 trended toward significance (p=0.05). Conclusion：APOA5 rs2075291 and CIDEB rs2144492  polymorphisms are associated with hypertriglyceridemia. Dampness syndrome individuals with CIDEB rs2144492 variants may have increased HTG predisposition. Larger cohort studies are warranted to validate these findings and explore underlying mechanisms.