The Flavin-Containing Monooxygenase 3 Gene and Essential Hypertension: The Joint Effect of Polymorphism E158K and Cigarette Smoking on Disease Susceptibility

Abstract

Gene encoding flavin-containing monooxygenase 3 (FMO3), a microsomal antioxidant defense enzyme, has been suggested to contribute to essential hypertension (EH). The present study was designed to investigate whether common functional polymorphism E158K (rs2266782) of the FMO3 gene is associated with EH susceptibility in a Russian population. A total of 2 995 unrelated subjects from Kursk (1 362 EH patients and 843 healthy controls) and Belgorod (357 EH patients and 422 population controls) regions of Central Russia were recruited for this study. DNA samples from all study participants were genotyped for the FMO3 gene polymorphism through PCR followed by RFLP analysis. We found that the polymorphism E158K is associated with increased risk of essential hypertension in both discovery population from Kursk region (OR 1.36 95% CI 1.09–1.69, P = 0.01) and replication population from Belgorod region (OR 1.54 95% CI 1.07–1.89, P = 0.02) after adjustment for gender and age using logistic regression analysis. Further analysis showed that the increased hypertension risk in carriers of genotype 158KK gene occurred in cigarette smokers, whereas nonsmoker carriers of this genotype did not show the disease risk. This is the first study reporting the association of the FMO3 gene polymorphism and the risk of essential hypertension.

Association of the -844G>A polymorphism in the catalase gene with the increased risk of essential hypertension in smokers

“…Имеется большое число публикаций, в которых установлены подобные генно-средовые взаимодействия, ассоциированные с развитием сердечно-сосудистой и другой патологии. Проведенные нами ранее исследова-ния показали, что курение является провоцирующим фактором развития диабетической ангиопатии у носите-лей генотипа 677ТТ гена MTHFR [19]; ген флавиновой монооксигеназы-3 ассоциирован с развитием АГ также только у курящих индивидуумов [16]. При анализе ассо-циации полиморфизма E298D гена NOS3 с развитием мозгового инсульта мы также обнаружили, что данный полиморфизм ассоциирован с заболеванием только у ку-рильщиков [20].…”

“…[14,15], а также пациенты, проходившие лечение в Региональном сосуди-стом центре Курской областной клинической больницы в 2012-2013 гг. [16,17]. Диагноз АГ устанавливался квалифицированны-ми кардиологами в соответствии с критериями Всемирной орга-низации здравоохранения.…”

A comprehensive study revealed SNP–SNP interactions and a sex-dependent relationship between polymorphisms of the CYP2J2 gene and hypertension risk

“…The discovery sample, including 1558 unrelated individuals (913 patients with EH and 645 age-and sex-matched healthy controls), was recruited from the Cardiology Clinics of Kursk Regional Clinical Hospital and the Neurology Clinics of Kursk Emergency Medicine Hospital. These study patients were enrolled during two study periods: the first period was between 2003 and 2006 and the second period was between 2007 and 2012 [34][35][36][37]. The control group included blood donors, healthy volunteers and hospital-based patients (all subjects were recruited from the surgical, traumatic, and infectious divisions of Kursk hos pitals) with normal blood pressure and without cardiovas cular or other chronic diseases.…”

“…The control group included blood donors, healthy volunteers and hospital-based patients (all subjects were recruited from the surgical, traumatic, and infectious divisions of Kursk hos pitals) with normal blood pressure and without cardiovas cular or other chronic diseases. The control group was recruited over the same periods of time [34][35][36][37][38]. To ensure an ethnically homogeneous population, only Russian resi dents living in Central Russia for at least two generations have been included in the study.…”

“…The replication population included DNA samples obtained from 756 unrelated Rus sian individuals (345 hypertensive patients and 411 con trols) as a part of the biobank of Belgorod State University. Detailed information regarding this population is described elsewhere [36].…”