Angiotensinogen Gene Polymorphisms M235T/T174M

Abstract

Abstract-The gene encoding angiotensinogen (AGT) has been widely studied as a candidate gene for hypertension. Most studies to date have relied on case-control analysis to test for an excess of AGT variants among hypertensive cases compared with normotensive controls. However, with this design, nothing guarantees that a positive finding is due to actual allelic association as opposed to an inappropriate control population. To avoid this difficulty in our study of essential hypertension in Anqing, China, we tested AGT variants using the transmission/disequilibrium test, a procedure that bypasses the need for a control sample by testing for excessive transmission of a genetic variant from parents heterozygous for that variant. We analyzed two AGT polymorphisms, M235T and T174M, which have been associated with essential hypertension in whites and Japanese, using data on 335 hypertensive subjects from 315 nuclear families and their parents. Except in the group of subjects younger than 25 years, M235 and T174 were the more frequently transmitted alleles. ypertension, a leading cause of cardiovascular and renal disease in the United States, results from a combination of genetic and environmental factors. Because of the public health significance of this disorder, many studies on the genetic basis of hypertension have been performed. 1-9 Several of these studies have tested genes with potential biological relevance to ascertain whether certain variants appear to influence the disease process. 3-9 One frequently studied gene has been angiotensinogen (AGT), a logical candidate, given the strong correlation of plasma angiotensinogen levels and blood pressure. 10 Located on 1q42 to 43, AGT comprises five exons and four introns spanning 13 kb. 11 Although several polymorphisms in the AGT region have been identified, 3 much interest has focused on two coding region polymorphisms, M235T and T174M, both in exon 2. More specifically, through case-control studies, many 3-5 but not all 6 -9 investigators have concluded that the threonine allele (T235) of M235T and the methionine allele (M174) of T174M are associated with elevated risk for hypertension. The validity of these case-control studies, however, depends on the ability of identifying a suitable control group, since different genetic backgrounds with varying polymorphism frequencies can potentially lead to spurious results.To eliminate the need for an external control group in our study of M235T and T174M in rural Chinese, we have collected nuclear families consisting of hypertensive individuals and their parents and have applied family-based association testing using the transmission/disequilibrium test (TDT). 12 With TDT, parental alleles transmitted to the affected hypertensive offspring are compared with those not transmitted. As a result, each family provides its own controls, and false-positives due to poorly matched controls are avoided.In addition to the sophistication of the TDT study design, the other defining feature of our investigation is the unique nature of ...

Association of Angiotensinogen T174M and M235T Gene Variants with Development of Hypertension in Turkish Subjects of Trakya Region

“…the RAS may be the most important of the endocrine system that affects the control of blood pressure (16,19). Some studies reported a possible influence of polymorphisms of genes encoding for components of the RAS such as the angiotensinogen (AGt) (30,33), the angiotensin converting enzyme (Ace) (10,28), and the angiotensin ii type 1 receptor (AtiR) on the onset of hypertension (15,38), while others did not (26,27,34). one frequently studied gene has been AGt, a logical candidate gene, given the strong correlation of plasma AGt levels and blood pressure (2,14).…”

Asociación y efectos de interacción en los genes AGT, AGTR1, ACE, ADRB2, DRD1, ADD1, ADD2, ATP2B1, TBXA2R y PTGS2 sobre la hipertensión en población antioqueña

“…Se han llevado a cabo numerosos estudios genéticos sobre estos sistemas; sin embargo, los resultados han sido incongruentes entre poblaciones, lo que evidencia la heterogeneidad de la hipertensión arterial en su etiología genética en las poblaciones continentales (45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58).…”

Association between the angiotensinogen gene T174M polymorphism and hypertension risk in the Chinese population: a meta-analysis

“…Among the 22 eligible articles, a study by Chiang et al 34 was replaced with a later report 21 that included a larger population. Moreover, Fang et al 35 and Niu et al [36][37][38] were excluded as they were family-based studies. In addition, the genotype data of the control population provided in He et al 39 was excluded, as it deviated from HWE (P HWE o0.0001).…”