Genetic and phenotypic frequency distribution of ACE, ADRB1, AGTR1, CYP2C9*3, CYP2D6*10, CYP3A5*3, NPPA and factors associated with hypertension in Chinese Han hypertensive patients

Abstract

We analyzed the polymorphisms of 7 antihypertensive drugs-related genes and the factors associated with hypertension in hypertensive patients of Han ethnicity in Qingyang, China. A total of 354 hypertensive patients of Han ethnicity were enrolled from Qingyang, China. The ACE (I/D), ADRB1 (1165G > C), AGTR1 (1166A > C), CYP2C9*3, CYP2D6*10, CYP3A5*3 and NPPA (T2238C) polymorphisms were assessed. Clinical data of patients was also obtained. The influencing factors of hypertension were evaluated. The genotype frequencies of ACE, ADRB1, AGTR1, CYP2C9, CYP3A5 and NPPA loci were in Hardy-Weinberg equilibrium, with mutation frequencies of 39.27%, 74.29%, 6.21%, 4.80%, 72.46% and 0.71%, respectively. CYP2D6 locus was not in Hardy-Weinberg equilibrium. There was no statistical difference in allele frequencies between different genders (P > .05). There was significant difference in the frequencies of ACE (I/D) and NPPA (T2238C) loci among different regions of China (P < .05). Gender, ACE (I/D) and ADRB1 (1165G > C) gene polymorphism, smoking, homocysteine and HDL levels were associated hypertension. The mutation frequencies of ADRB1 (1165G > C) and CYP3A5*3 were high in hypertensive patients of Han ethnicity in Qingyang, suggesting these patients may be more sensitive to beta-blockers and calcium ion antagonists. Meanwhile, hypertension was associated with gender, ACE (I/D) and ADRB1 (1165G > C) gene polymorphisms, smoking, homocysteine and HDL levels. Abbreviations: ACEI = angiotensin-converting enzyme inhibitor, ADA = adenosine deaminase, ALT = alanine aminotransferase, BUN = urea nitrogen, Cre = creatinine, Hcy = homocysteine, HWE = Hardy-Weinberg equilibrium, HDL-C = high density lipoprotein cholesterol, LDL-C = low density lipoprotein cholesterol, NPPA = natriuretic peptide precursor protein A, RBP = retinol binding protein, TC = total cholesterol, UA = uric acid, γ-GGT = γ-glutamyl aminotransferase.

Genetic diet interactions of ACE: the increased hypertension predisposition in the Latin American population

“…Additionally, in the province where the study was performed, the diet included a high salt intake, and when the participants were overweight, the risk increased, suggesting a correlation between diet, obesity, and hypertension ( 34 ). These results align with those of Wang et al ( 32 ), where a correlation between a high-salt diet and increased hypertension prevalence was described ( 32 ). More studies regarding the impact of rs4343 have been performed for different populations, including samples from Europe, and Asia, with similar outcomes, associating rs4343 with an increased hypertension risk ( 35 ).…”

“…As previously described, the ACE gene has been strongly associated with hypertension ( 7 , 32 ). Moreover, single nucleotide polymorphisms (SNPs) within the gene have also been correlated with disease risk to varying degrees based on factors such as diet, individual traits, race, and region ( 7 ).…”

“…Hypertension incidence is growing worldwide, and factors such as population aging, obesity, and an unhealthy diet, further increase the issue ( 7 , 41 ). Furthermore, the genetic composition of a population could also significantly increase hypertension predisposition ( 32 ), highlighting the importance of gene–environment interactions involved in this disease. Moreover, LMICs are the most affected by the increase in hypertension prevalence, with more than 1.04 billion people living with this disease in these regions ( 42 ).…”

Association of Antihypertensive Drug-Related Gene Polymorphisms with Stroke in the Chinese Hypertensive Population

“…In addition, we observed that CYP2D6∗10 , AGTR1 ( 1166A > C ), and NPPA ( 2238T > C ) genes do not conform to the Hardy–Weinberg equilibrium test. Another study conducted in Chinese Han hypertensive patients also found that CYP2D6∗10 was not in HWE [ 16 ]; this might be because CYP2D6∗10 , AGTR1 ( 1166A > C ), and NPPA ( 2238T > C ) genes were associated with the development of hypertension [ 23 , 35 , 36 ]. Studies revealed that alleles associated with disease etiology often deviate from the expected allele or genotype frequency [ 37 ].…”

“…Certain genotypes exhibit a greater reduction in blood pressure (BP) and/or long-term benefit with antihypertensive drug use [ 15 ]. In particular, the CC genotype of ADRB1 ( 1165G > C ), DD genotype of ACE ( I / D ), C allele carrier of AGTR1 ( 1166A > C ), and NPPA ( 2238T > C ) are reported to be associated with a significant reduction in BP [ 16 – 19 ]. Mutations in cytochrome P450 enzyme family members, such as CYP2D6 , CYP2C9 , and CYP3A5 , mainly affect the activities of metabolic enzymes.…”