Table 3.
Single nucleotide polymorphisms associated with BP response in genome-wide association analyses of amlodipine-treated patients
| Gene | SNP | Treatment outcome | Population | References |
|---|---|---|---|---|
| ABCB1 | rs1045642 | Gender differences and SNPs in ABCB1 gene (2677G/T and 3435C/T) showed increased oral clearance of amlodipine. Males require higher concentration of amlodipine. |
Asian | [40, 41] |
| ACE | rs200148 rs4291 |
For SNP rs200148 in the African-American cohort, the A allele frequency is higher in the chlorthalidone treatment group as compared to the amlodipine group. Promoter mutations in rs4291 were associated with lower fasting glucose for the model AA/AT compared to the TT. |
African-American and Caucasian | [42] |
| CACNA1D | rs312481 rs3774426 |
A significant reduction in BP was observed for the combined presence of the identified SNPs (rs312481G/A and rs3774426C/T). Individuals with CC genotype responded better as measured by lowered SBP. |
Asian | [43, 44] |
| CACNA1C | rs527974 rs2239050 and rs2238032 |
Identified SNP 527974G/A was able to decrease BP significantly after treatment. However, none of the identified SNPs were similar to those identified in the Brenner study. | Asian | [43–45] |
| Estonian Genome Project found that patients with the combined identified SNP had an increased efficacy to amlodipine treatment outcome. | Caucasian | |||
| CYP3A4 | rs2246709 rs2740574 |
Blood pressure response was gender specific and associated with African-American population with genotypes (16090T/C and 392 A/G). | African-American and | [22, 42, 46–48] |
| Gender differences was observed but not significant and, CYP3A5*3 does not affect amlodipine efficacy. | Asian | |||
| CYP3A5 | rs776746 |
CYP3A5 6986A/G was not associated with decrease in BP response in African-American population. But, a significant reduction in BP occurred in Chinese and Korean cohort, CYP3A5*3/*3 carriers exhibited lower plasma amlodipine concentrations than CYP3A5*1 carriers. Gender differences was observed but not significant and, CYP3A5*3 does not affect amlodipine efficacy. |
African-American/Asian | [46–49] |
| GNB3 | rs5443 | Splice variant is associated with the DBP lowering effect of telmisartan but not amlodipine in Chinese. | Asian | [50] |
| MDR1 | G2677T/C3435T | Discordant results with the C3435T found that the plasma drug concentration of amlodipine in healthy volunteers of the MDR1 C3435T mutant allele carrier was lower than that of the CC type. However, according to the study of Cai and colleagues, the MDR1 C3435T mutant did not influence the effect of amlodipine in renal transplant patients with hypertension. Therefore, further investigations are required to elucidate the impact of the MDR1 C3435T polymorphism on the pharmacokinetics and efficacy of amlodipine. | Caucasian and Asian | [42, 51] |
| NOS1AP | rs10494366 | Significance (SNPs at this gene as relevant to stroke pharmacogenetics. | African-American | [52] |
| NPPA | rs5065 | The 2238T/C variant had lower event rates were for the C allele carriers than for the TT homozygous when comparing chlorthalidone and amlodipine. The AA genotype responds better to amlodipine. | Multiple races and ethnic groups | [53] |
| NUMA1 | rs10898815 | Increased response as determined by a greater decrease in DBP but SBP blood pressure. | Multiple races and ethnic groups | [44] |
| PICALM | rs588076 | Patients with the GG genotype and hypertension may have a greater decrease in blood pressure. | Multiple races and ethnic groups | [44] |
| POR | rs1057868 | 1509 C/T genotypes had no significant impact on the blood drug concentration and efficacy of amlodipine due to sample size. | Asian | [42] |
| RYR3 | rs877087 | Reduced BP response was observed. | Caucasian | [54] |
| TANC2 | rs2429427 | Reduced BP response was observed. | Multiple races | [44] |
ABCB1 ATP-binding cassette subfamily B member 1, ACE angiotensin I converting enzyme, AGT angiotensinogen, CACN1D calcium channel voltage-dependent, L type, alpha 1D subunit, CACNA1C calcium channel voltage-dependent, L type, alpha 1C subunit, CYP3A4 cytochrome P450 family 3 subfamily A member 4, CYP3A5 cytochrome P450 family 3 subfamily A member 5, GNB3 G Protein Subunit Beta 3, NOS1AP Nitric Oxide Synthase 1 Adaptor Protein, NPPA Natriuretic Peptide A, NUMA1 nuclear mitotic apparatus protein 1, PICALM phosphatidylinositol binding clathrin assembly protein, POR cytochrome p450 oxireductase, RYR3 Ryanodine Receptor 3, TANC2 tetratricopeptide repeat, ankyrin repeat and coiled-coil containing 2