Genetic Variation in ABCB1 , ADRB1 , CYP3A4 , CYP3A5 , NEDD4L and NR3C2 Confers Differential Susceptibility to Resistant Hypertension among South Africans.

Resistant hypertension (RHTN) prevalence ranges from 4 to 19% in Africa. There is a paucity of data on the role of genetic variation on RHTN among Africans. We set out to investigate the role of polymorphisms in ABCB1 , ADRB1 , CYP3A4 , CYP3A5 , NEDD4L, and NR3C2 , on RHTN susceptibility among South Africans. Using a retrospective matched case-control study, 190 RHTN patients (cases: blood pressure (BP) ≥ 140/90 mmHg on ≥3 anti-hypertensives or BP < 140/90 mmHg on >3 anti-hypertensives) and 189 non-RHTN patients (controls: <3 anti-hypertensives, BP < 140/90 or ≥140/90 mmHg), 12 single nucleotide polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), quantitative PCR and Sanger sequencing. Genetic association analyses were conducted using the additive model and multivariable logistic regression. Homozygosity for CYP3A5 rs776746C/C genotype ( p = 0.02; OR: 0.44; CI: 0.22-0.89) was associated with reduced risk for RHTN. Homozygous ADRB1 rs1801252G/G ( p = 0.02; OR: 3.30; CI: 1.17-10.03) and NEDD4L rs4149601A/A genotypes ( p = 0.001; OR: 3.82; CI: 1.67-9.07) were associated with increased risk for RHTN. Carriers of the of ADRB1 rs1801252-rs1801253 G-C haplotype had 2.83-fold odds of presenting with RHTN ( p = 0.04; OR: 2.83; CI: 1.05-8.20). These variants that are associated with RHTN may have clinical utility in the selection of antihypertensive drugs in our population.