PDIA3 rs2788, a risk factor for metabolic syndrome, interacted negatively with antihypertensive medications

The clinical complex called metabolic syndrome (MetS) is caused by the interaction of genetic and cardiovascular risk factors. Protein disulfide isomerase family A member 3 (PDIA3) is a key endoplasmic reticulum protein which may contribute to MetS. This study aimed to evaluate how PDIA3 polymorphism is linked to MetS and its hypertension. Clinical indicators were measured in 2,379 individuals. The association of PDIA3 rs2788 with MetS was analyzed. Crossover analysis elucidated the crosstalk between PDIA3 rs2788 and antihypertensive treatment, and the synergistic effect on MetS. In this cross-sectional study, linear regression analysis showed that a positive linear correlation of rs2788 with systolic blood pressure (SBP, β = 5.818, p < 0.01) and diastolic blood pressure (DBP, β = 4.324, p < 0.01). Ordered logistic regression revealed that the rs2788 GG genotype was progressive with an increasing number of MetS components (component number: 2-5, both p < 0.05). In the longitudinal analysis, a multivariate logistic regression model adjusted for variable MetS components revealed that PDIA3 rs2788 confers a high risk of MetS incidence (OR: 1.585, 95% CI: 1.011-2.486; p < 0.05). Stratification analysis revealed that PDIA3 rs2788 correlated positively with SBP and DBP among female patients. The synergistic effect of antihypertensive treatment and PDIA3 rs2788 is negative among female patients (S < 1). PDIA3 rs2788 is a strong predictor for MetS in the studied Chinese population. In female patients, PDIA3 rs2788 interacted negatively in the association of MetS with antihypertensive treatment.