Angiotensin II type 1 receptor A1166C gene polymorphism and essential hypertension in Calabar and Uyo cities, Nigeria.

OBJECTIVES: The angiotensin II protein is a vasoconstrictor that exerts most of its influence through the angiotensin II type 1 receptor (AT1R). Inconsistent association between the A1166C polymorphism of the AT1R gene and hypertension has been reported among various populations but not among the peoples of Calabar and Uyo. This study was designed to determine the frequency of the A1166C polymorphism of the AT1R gene and its association with hypertension in a sample population of Calabar and Uyo. MATERIALS AND METHODS: A population-based case control design consisting of total of 1224 participants, 612 each of patients and controls were randomly recruited from hypertension clinics and the general population. Genotyping of the A1166C allele of the AT1R gene to identify variants was performed using polymerase chain reaction and restriction enzyme digestion. Multiple regressions were applied to test whether the A1166 genotypes were predictors of hypertension. RESULTS: 99% of the study population had the wild type AA genotype, and 1% was AC heterozygous carriers of the A1166C polymorphism. CONCLUSION: The A1166C polymorphism was not a predictor of hypertension in the sample population of Calabar and Uyo.

Angiotensin converting enzyme I/D, angiotensinogen T174M-M235T and angiotensin II type 1 receptor A1166C gene polymorphisms in Turkish hypertensive patients

Essential hypertension is a multifactorial disease in which genetic and enviromental factors play an important role. These factors differ in each population. As there are no existing data for the Turkish population, we investigated four Renin Angiotensin System (RAS) gene polymorphisms, the angiotensin converting enzyme (ACE), angiotensinogen (AGN) M235T/T174M and angiotensin II type 1 receptor A1166C polymorphism in 109 hypertensive and 86 normotensive Turkish subjects. Polymerase Chain Reaction (PCR) and Restriction Fragment Length Polymorphism (RFLP), and agarose gel electrophoresis tecniques were used to determine these polymorphism. The frequencies of person that carry ACE D allel (DD+ID) was significantly higher in hypertensive group (99.1%) than controls (80%) (P<0.000). M235T TT genotype was also found significantly higher in hypertensives than control group (20% vs 2.7%; P<0.001). The frequency of AGN 174M allele was higher in the hypertensive group than control subjects (8.76% vs 4.81%). Frequency of ATR1 C allele (AC+CC genotypes) was found higher hypertensives than controls (39.4% vs 25.9%; P = 0.054). Our results suggest that an interaction exists between the RAS genes and hypertension in Turkish population.

Analysis of A1166C Polymorphism in Type I Receptor for Angiotensin II Gene with Pregnancy Induced Hypertension(PIH) in Korean Women / 대한주산의학회잡지

BACKGROUND/AIM: Recent studies have suggested an association between genetic background of renin-angiotensin(RA) system and the pathogenesis of pregnancy induced hypertension(PIH). Even though various single nucleotide polymorphism(SNP) such as M235T, T174M polymorphism in angiotensinogen gene(AGT) and I/D polymorphism in angiotensin I-converting enzyme gene(ACE) have been studied extensively among essential hypertension and PIH in various population, its association was still inconclusive. Previous studies within Korean PIH patients also revealed that M235T or T174M single nucleotide polymorphism in AGT gene or I/D polymorphism in ACE gene were not linked tightly with PIH. However, recent studies on angiotensin II type I receptor(AT1) polymorphism A1166C with PIH in Polish or in Chinese suggested its possible correlations to a pathogenesis of PIH. Thus the aim of the present study was to determine the frequency of genotypes of A1166C mu-tation in women with PIH and to establish the role of this polymorphism on the susceptibility to the PIH development. PATIENTS AND METHODS: We have analysed 121 women with PIH and 98 healthy normotensive gravid women as a control. Genomic DNA was used for PCR. To genotype the A1166C polymorphism in angiotensin II receptor(AT1) gene, primers(sense 5'-CGA CTA CTG CTT AGC ATA-3', antisense 5'-GCA CCA TGT TTT GAG GTT-3') were employed to make 546bp PCR product. There was an initial denaturation at 94degrees C 5 minutes, followed by 30 cycles of one minute at 94degrees C, one minute at 58degrees C, and two minutes at 7degrees C. A 546bp PCR product was further digested with DdeI for 2 hour at 37degrees C and analysed through 2% agarose gel electrophoresis to determine genotype. Allele C1166 yielded 435bp, 111bp fragment and allele A1166 yielded intact 546 bp fragment RESULTS: We found that frequency of genotype A1166/C1166 and A1166/A1166 in PIH were 9.9% (12) and 90.1%(109), while in controls were 17.3%(17) and 82.7%(81). There was no statistical significance between development of PIH and A1166C polymorphism in type I receptor for Angiotensin II. Homozygous mutated genotype(C1166/C1166) was not detected in this study. CONCLUSION: Our results found no possible correlation of A1166C polymorphism in angiotensin II receptor(AT1) with PIH in Korean and found that allele C might behave as a protective factor rather than as a risk factor in the pathogenesis of PIH. We suggest a large-scale study to evaluate relevance to this polymorphism for PIH.