The role of the rs2297518 of NOS 2 gene as a genetic biomarker of arterial hypertension and “arterial hypertension and tension-type headache” phenotype (the pilot study in East Siberia)

Nitric oxide (NO) plays an important pathogenetic role in vascular relaxation and is a candidate molecule of a common pathogenetic link in the development of arterial hypertension (AH) and tension-type headache (TTH).

Objective of the study was to study the association of the single nucleotide variant (SNV) rs2297518 of the NOS 2 gene with the risk of developing AH and clinical “AH + TTH” phenotype in adults living in a large industrial city of Eastern Siberia.

Design and methods. All participants (N = 91) were divided into two groups: group 1 (patients with AH) — 60 people, including the main subgroup (patients with AH without headache) — 30 people and a comparable subgroup (patients with clinical phenotype “AH + TTH”) — 30 people; group 2 (control — healthy volunteers) — 31 people. Carriage of the SNV rs2297518 gene NOS 2 (locus 17q11.2) was determined using real-time polymerase chain reaction.

Results. The minor allele A rs2297518 of the NOS 2 gene was statistically significantly associated with a high risk of developing AH (odds ratio (OR) = 8,43 [95 % confidence interval (CI): 2,33–30,46], p = 0,000223) and phenotype “AH + TTH” (OR = 5,44 [95 % CI: 1,46–20,21], p = 0,006) compared with the control group. The heterozygous genotype GA rs2297518 of the NOS 2 gene also was statistically significantly associated with a high risk of developing AH (OR = 8,17 [95 % CI: 2,03–32,79], p = 0,001).

Conclusions. The study demonstrated that the minor allele A of the SNV rs2297518 (26096597 G > A) of the NOS 2 gene, which encodes the inducible NO-synthase (iNOS), can be considered as a clinically significant genetic biomarker, first of all, of AH in the Caucasian population of Eastern Siberia. At the same time, future studies may clarify the role of this SNV as a genetic biomarker of the “AH + TTH” phenotype.

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