A polymorphism inAGTandAGTR1gene is associated with lead-related high blood pressure

Abstract

We investigated the association of polymorphisms in two renin-angiotensin system-related genes, expressed as angiotensinogen (AGT) and angiotensin II type 1 receptor (AGTR1), with blood lead levels and lead-related blood pressure in lead-exposed male workers in Korea. A cross-sectional study involving 808 lead-exposed male workers in Korea was conducted using a restriction fragment length polymorphism-based strategy to differentiate the various genotypes of polymorphisms in the AGT and AGTR1 genes. The association of clinical characteristics with genotypes as modifiers was estimated after adjustment for age, smoking status, drinking status, body mass index and job duration of each subject. Genotype and allele frequencies of the M235T polymorphism in AGT were associated with lead-related high blood pressure status. Moreover, blood lead levels were associated with allele frequencies of the AGT M235T polymorphism. These results suggested that the M/M genotype and M allele of AGT are risk factors for lead-related high blood pressure.

The association between angiotensin II type 1 receptor A1166C gene polymorphism and the risk of essential hypertension: a meta-analysis

“…A1166C is located at the 5′ end of the 3′ untranslated region of the gene [72]. This location is a non-coding region of AT1R, and it is linked to disequilibrium with a nearby mutation that may affect AT1R messenger ribonucleic acid (mRNA) stability [32]. In essential hypertension, the C allele of A1166C was revealed to have a pivotal role for influencing AT1R activities through affecting mRNA stability and transcription or alternatively be linked to other SNPs [65].…”

Analysis of Polymorphisms of Renin-Angiotensin-Aldosterone System and Relation to Vasopressors in Essential Systemic Hypertension With the Left Ventricle Hypertrophy in Dagestan Republic

“…В связи с этим, обращение многих исследо-вателей к изучению генетических основ гипертрофии кардиомиоцитов вполне обоснованно и перспек-тивно. Получены многочисленные, крайне важные результаты роли полигенных нарушений в течении и исходе ЭАГ и ассоциаций полиморфизмов генов РААС, симпатоадреналовой системы, генов, ответ-ственных на синтез сократительных белков кардио-миоцитов и др., с фактом ГЛЖ [8,9,11,12,14]. Отли-чительными особенностями результатов этих популя-ционно-генетических исследований являются уникальность распределения частот полиморфизмов генов-кандидатов в зависимости от этнической, ген-дерной принадлежности, а также географического района проживания исследуемых пациентов.…”

“…Генотипирование полимор-физмов Тhr174Мet и Мet235Тhr гена AGT, полимор-физм A1166C гена AGTR1 проводили с использова-нием наборов для генотипирования "SNP-ЭКС-ПРЕСС-РВ-Кардиогенетика". Согласно инструкции к этому набору, с образцом выделенной ДНК прово-дили одновременно две реакции амплификации -но полиморфизмы AGTR1 не имели статистически доказанной связи с ГЛЖ [12]. Исследование Т174М полиморфизма гена AGT показало более высокую распространенность М-аллеля в гомозиготном состо-янии у больных АГ с ГЛЖ [13].…”

Lead-Related Genetic Loci, Cumulative Lead Exposure and Incident Coronary Heart Disease: The Normative Aging Study

“…A number of genes and gene encoding proteins have been identified to play important roles in lead toxicokinetics and/or toxicodynamics: δ-aminolevulinic acid dehydratase (ALAD), an enzyme on the heme-biosynthetic pathway that binds over 80% of lead in erythrocytes [9]; hemochromatosis (HFE), a membrane protein that regulates uptake of cellular iron and other divalent metals including lead [10]; heme oxygenase-1 (HMOX1), a heme-degrading enzyme that plays an important role in the inflammation and oxidative stress induced by lead [11][12][13][14]; vitamin D receptor (VDR) that plays a role in calcium homeostasis that influences the absorption and retention of lead into blood and bone [15]; apolipoprotein E (APOE) that affects lipid metabolism, down-regulates blood lead concentrations, and possesses antioxidative property [16][17][18]; glutathione S-transferases (GSTs), a family of phase-II detoxification isozymes involved in catalyzing the conjugation of lead and glutathione to form a thermodynamically stable complex, which decreases lead bioavailability and protects against lead toxicity through reduced oxidative stress [19][20][21][22]; and the renin-angiotensin system involved in the development of hypertension where lead exposure may enhance blood angiotensin I levels by increasing plasma renin activity, which in turn contribute to production and activation of substrate-induced angiotensin converting enzyme [23,24]. Epidemiologic studies have identified that these genes may modify the association between lead exposure and cardiovascular and other health outcomes [13,18,[25][26][27]. However, these previous studies focused on one or a few of the lead-related genetic polymorphisms.…”