English abstract
Hypertension is one of the most common complex diseases around the world. It results from the interaction of genetic and environmental factors. Previous studies have shown high prevalence of this disease in Oman (21%). In this study, association of 5 SNPs in 3 candidate genes with BP and haemodynamic parameters was tested. The studied population here is an extended pedigree of low admixture (294 members) from an Omani family study is Nizwa district. The family members were phenotypically characterized in the hypertension (HTN) project. Out of the 294 subjects in the pedigree, 232 were normal (106 males & 126 females) and the rest 62 were hypertensives (37 males & 25 females)
The major objective of this study was to test association between selected SNPs in several hypertension candidate genes and different haemodynamic parameters. Previous linkage and association studies on hypertension and BP regulation were the main guides in gene selection. Each of the selected genes should encode a protein that has a known function in BP regulation. The gene locus should have been linked to BP phenotypes in at least 3 independent previous linkage studies. The selected polymorphism in the gene should cause a functional change to the encoded product. Also, it should have been associated to BP variation in 3-5 independent previous association studies or validated in relation to BP in animal experimental studies. Based on these, the following SNPs were selected: E65K and VIIOL in the beta subunit of calcium sensitive potassium channel (KCNMBI), G442V and 7594M in the beta subunit of epithelial Sodium channel (ENaC), and G460W in alpha adducin (ADDI). SNP genotyping was done by RFLP except for the G460W SNP in the ADDI gene, which was detected by automated sequencing, Association between each genotype and different haemodynamic parameters was tested assuming that the study is population Based For cach SNP, the genotype and allelic frequency was calculated. The frequency of mutant alleles of the SNPs E65K, VITOL, G442V. 7594M and G460W was found to be:
0.07, 0.08, 0.04, 0.01 and 0.04 respectively. Generally, the frequency for all mutant alleles was in the lower side compared to other populations, For all SNPs, there was no difference between normal and hypertensive subjects in the frequency of mutant alleles.
In SCNNIB gene, the G442V variant was significantly associated with increased systolic and mean blood pressure at night-time (P:0.042, 0.015) and decreased baroreceptor sensitivity (P: 0.038). The 7594M variant was associated with high sympathovagal balance (LF/HF ratio, P: 0.008). In KCNMB1 gene, there was an association between the E65K variant and decreased R-R interval, LF, HF and increased heart rate at rest (P: 0.004, 0.001, 0.007, and 0.004 respectively). The V110L variant was associated with a higher BMI (P: 0.013) and lower HF and LF values (P: 0,028& 0.026). No significant association was detected between the G460W SNP in the ADDI gene and BP variation or different haemodynamic parameters In summary, the ADDI gene may not play a role in the development of hypertension in Omanis, but the KCNMBI and SCNNIB genes appear to have an important role regulating blood pressure in this population.
