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Background H-type hypertension seriously affects people's health and quality of life. Currently, the clinical treatment of hypertension mainly selects drugs based on the experience, and the antihypertensive effect is not ideal. It is urgent to explore the pharmacogenetic polymorphisms of antihypertensive drugs and provide individualized medication guidance for hypertensive patients. Objective To investigate pharmacogenetic polymorphisms and the intervention effects of folic acid combined with vitamin D in patients with H-type hypertension in Jinan community, and provide reference for the implementation of integrated precision medicine for hypertension. Methods From June 2020 to June 2022, 200 hypertensive patients with poorly controlled blood pressure in 20 community health service centers of Huaiyin District, Jinan City, Shandong Province were randomly selected as the research objects. Before treatment, the gene polymorphisms of five commonly used individualized antihypertensive drugs, including diuretics, β-blockers, angiotensin-converting enzyme inhibitors (ACEI) , calcium channel inhibitors (CCB) , angiotensin-Ⅱ receptor antagonists (ARB) , were detected. Patients were randomly divided into the gene-directed treatment group (genome group) and gene-directed synergistic folic acid and vitamin D treatment group (gene-directed group) , with 100 cases in each group. The genome group adjusted the drug according to the characteristics of the detected hypertension gene loci; the gene-directed group received folic acid and vitamin D in addition to the genomic therapy regimen. Sitting systolic and diastolic blood pressures in the morning without antihypertensive drugs were collected from patients at the initial intervention (M0) , 3 months of intervention (M3) , and 6 months of intervention (M6) . Case status, adverse reactions and stroke were recorded, gene sequencing was performed, and serum homocysteine (Hcy) concentration was detected. Pearson correlation analysis or Spearman's rank correlation analysis were used to explore the correlation between sex, age, systolic blood pressure, diastolic blood pressure and Hcy. Results Gender (rs=-0.463) , systolic blood pressure (r=0.181) and diastolic blood pressure (r=0.188) were correlated with Hcy level (PC) , CYP2D6 (c.100C>T) were associated with polymorphism loci of drug metabolism enzyme genes, respectively. ADRB1, ACEI (I/D) , AGTR1 and NPPA were associated with the polymorphic loci of drug target sensitivity genes. Genome A6986G:CYP3A5*1/*1 (AA) , ACEI (I/D) :D/D, C.100 C>T:CYP2D6*1/*1 (CC) patients at M3 and M6 had lower diastolic blood pressure than M0, A6986G:CYP3A5a1/a3 (AG) , ADRB1 C.1165 G>C:GG, c.1075A>C:CYP2C9*1/*3 (AC) , c.1075A>c:CYP2C9*3/*3 (CC) patients at M6 had lower systolic and diastolic blood pressure than M0, A6986G:CYP3A5*3/*3 (GG) , ADRB1 C.1165 G>C:CC, ACEI (I/D) :I/I, c.1075A>C:CYP2C9*1/*1 (AA) , AGTR1 C.1166A>c:AA, NPPA T2238C:TT, c.100 C>T:CYP2D6*10/*10 (TT) patients at M3 and M6 had lower systolic and diastolic blood pressure than M0, ADRB1 C.1165 G>C:GC, ACEI (I/D) :I/D, c.100 C>T:CYP2D6*1/*10 (CT) patients at M6 had lower systolic blood pressure than M0, and lower diastolic blood pressure than M0, the difference was statistically significant (P