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Genetic profiling will probably lead to the redefinition of the RH paradigm and
introduce different diagnosis criteria, identifying an entity by the gene/cluster
involved and not by number of antihypertensive drugs, which will consequently
determine adequate tailoring of treatment or even the design of new therapeutic
solutions (e.g., vaccine).
To date, we cannot attempt an exhaustive description of gene mechanisms
involved, not for RH population subgroup and even more not for the entire essential
hypertension population, as we are in the midst of a hunting for genes direction. The
Millennium Genome Project (MGP) for Hypertension launched at the beginning of
2000 is a complex endeavor, aiming to identify genetic variants conferring suscep-
tibility to hypertension, in the attempt of enriching knowledge and understanding of
HT etiopathogenesis and designing genome-based personalized medical care. The
investigation approach is based on two different multilateral directions: (1) genome-
wide association analysis (GWAS) using single nucleotide polymorphisms (SNPs)
and microsatellite markers and (2) systematic candidate gene analysis, based on the
hypothesis that common variants play a significant role in the etiopathogeny of
common diseases. These approaches singled out ATP2B1 as gene responsible for
hypertension in Japanese and Caucasian populations. The increased risk for high
blood pressure granted by specific alleles of ATP2B1 has been widely replicated in
several populations [ 185 ].
However, the simple identification of genetic variants may not fully explain the
complexity of RH etiopathogenic mechanisms, since their effects may be influenced
by gene-gene or gene-environment interactions. A suggestive example is a recent
study which assessed the interaction between gene polymorphisms for ACE
(rs1799752), angiotensinogen (M235 T, rs 699), and nitric oxide endothelial syn-
thase (Glu 298Asp, rs 1,799,983) and environmental factors (age, gender, biologic
parameters), reporting that the AGT 235 allele represents an independent risk factor
for RH, especially associated with over 50 years of age [ 186 ].
Both in essential and resistant hypertension, gene analysis reveals the involve-
ment of several genes and interactions between genes and nongenetic factors, as
opposed to monogenic conditions where genetic analysis can be complete and clear.
Currently, the gathering of extensive collections of SNPs which can be used as
markers in GWA studies with the aim to identify hypertension susceptibility loci.
Therefore, it is expected that markers interrogating SNPs involved in inheritance of
disease susceptibility will emerge through their association with this trait in the
afflicted population [ 187 ].
There are large studies comprising genetic subinvestigations which have exam-
ined antihypertensive treatment in essential HT and considered the reasons for the
lack of response to various medication classes (NORDIL, GITS, INSIGHT – cal-
cium –antagonists, GENRES, and MILAN, diuretics). Furthermore, the analysis of
response to diuretic (hydrochlorothiazide) is based on SNPs (in PEAR and GERA
studies), while in pharmacogenomics studies it is investigated response to beta
blockers and diuretics [ 188 , 189 ].
A. Burlacu and A. Covic