Association of Single-Nucleotide Polymorphisms Rs2779249 (chr17:26128581 C>A) and Rs rs2297518 (chr17: chr17:27769571 G>A) of the NOS2 Gene with Tension-Type Headache and Arterial Hypertension Overlap Syndrome in Eastern Siberia

Polina V Alyabyeva; Marina M Petrova; Diana V Dmitrenko; Natalia P Garganeeva; Galina A Chumakova; Mustafa Al-Zamil; Vera V Trefilova; Regina F Nasyrova; Natalia A Shnayder

doi:10.3390/genes14020513

Association of Single-Nucleotide Polymorphisms Rs2779249 (chr17:26128581 C>A) and Rs rs2297518 (chr17: chr17:27769571 G>A) of the NOS2 Gene with Tension-Type Headache and Arterial Hypertension Overlap Syndrome in Eastern Siberia

Genes (Basel). 2023 Feb 17;14(2):513. doi: 10.3390/genes14020513.

Authors

Polina V Alyabyeva¹, Marina M Petrova¹, Diana V Dmitrenko¹, Natalia P Garganeeva², Galina A Chumakova³, Mustafa Al-Zamil⁴, Vera V Trefilova⁵, Regina F Nasyrova⁶, Natalia A Shnayder^{1

6}

Affiliations

¹ Shared Core Facilities Molecular and Cell Technologies, V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 660022 Krasnoyarsk, Russia.
² Department of General Medical Practice and Outpatient Therapy, Siberian State Medical University, 634050 Tomsk, Russia.
³ Department of Therapy and General Medical Practice with a Course of Postgraduate Professional Education, Altai State Medical University, 656038 Barnaul, Russia.
⁴ Department of Physiotherapy, Faculty of Continuing Medical Education, Peoples' Friendship University of Russia, 117198 Moscow, Russia.
⁵ Neurological Department No. 16, Hospital for War Veterans, 193079 St. Petersburg, Russia.
⁶ Institute of Personalized Psychiatry and Neurology, V.M. Bekhterev National Medical Research Center for Psychiatry and Neurology, 192019 St. Petersburg, Russia.

Abstract

Inducible nitric oxide (NO) synthase (iNOS), encoded by the NOS2 gene, promotes the generation of high levels of NO to combat harmful environmental influences in a wide range of cells. iNOS can cause adverse effects, such as falling blood pressure, if overexpressed. Thus, according to some data, this enzyme is an important precursor of arterial hypertension (AH) and tension-type headache (TTH), which are the most common multifactorial diseases in adults. The purpose of this study was to investigate the association of rs2779249 (chr17:26128581 C>A) and rs2297518 (chr17: chr17:27769571 G>A) of the NOS2 gene with TTH and AH overlap syndrome (OS) in Caucasians in Eastern Siberia. The sample size was 91 participants: the first group-30 patients with OS; the second group-30 patients AH; and the third group-31 healthy volunteers. RT-PCR was used for the determination of alleles and genotypes of the SNPs rs2779249 and rs2297518 of the NOS2 gene in all groups of participants. We showed that the frequency of allele A was significantly higher among patients with AH compared with healthy volunteers (p-value < 0.05). The frequency of the heterozygous genotype CA of rs2779249 was higher in the first group vs. the control (p-value = 0.03), and in the second group vs. the control (p-value = 0.045). The frequency of the heterozygous genotype GA of rs2297518 was higher in the first group vs. the control (p-value = 0.035), and in the second group vs. the control (p-value = 0.001). The allele A of rs2779249 was associated with OS (OR = 3.17 [95% CI: 1.31-7.67], p-value = 0.009) and AH (OR = 2.94 [95% CI: 1.21-7.15], p-value = 0.015) risks compared with the control. The minor allele A of rs2297518 was associated with OS (OR = 4.0 [95% CI: 0.96-16.61], p-value = 0.035) and AH (OR = 8.17 [95% CI: 2.03-32.79], p-value = 0.001) risks compared with the control. Therefore, our pilot study demonstrated that the SNPs rs2779249 and rs229718 of the NOS2 gene could be promising genetic biomarkers for this OS risk in Caucasians from Eastern Siberia.

Keywords: NOS2; biomarker; hypertension; iNOS; overlap syndrome; rs2779249; single-nucleotide polymorphism; tension-type headache.

MeSH terms

Adult
Autoimmune Diseases*
Genetic Predisposition to Disease
Humans
Hypertension* / genetics
Nitric Oxide Synthase Type II / genetics
Pilot Projects
Polymorphism, Single Nucleotide
Siberia
Tension-Type Headache*

Substances

NOS2 protein, human
Nitric Oxide Synthase Type II

Grants and funding

This research received no external funding.