PubMed · 11026321
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
T Ishigami, S Umemura. 2000. [Angiotensinogen gene].. https://pubmed.ncbi.nlm.nih.gov/11026321/
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
AIMS: Angiotensinogen plays an essential role in maintaining circulatory homeostasis. AGT rs5050(T > G) has been identified as a regulator of the transcription of AGT mRNA, with differential expression between sexes. We sought to determine if rs5050(T > G), an estrogen response element, modifies the relationship between estrogen and angiotensinogen levels. METHODS: rs5050(T > G) was genotyped, and plasma angiotensinogen levels were measured in 4,831 MESA participants, including postmenopausal women, on hormone therapy (n = 709) or not (n = 1,551), and 2,581 men. Linear regression models were employed to determine the associations of angiotensinogen with rs5050(T > G) allele dosage; and to evaluate whether rs5050(T > G) modifies the association between estradiol and angiotensinogen, with a main effect term and interaction term between rs5050(T > G)*estradiol. Estimated marginal means (EMMs) were used to further evaluate the effect of estradiol on angiotensinogen across different rs5050 alleles (T > G). RESULTS: rs5050TT had the highest median levels of angiotensinogen, followed by TG and GG. Adjusted main effect model showed positive associations between estradiol and angiotensinogen, with each rs5050T allele associated with 0.329 SD higher log-angiotensinogen levels (CI 95% 0.293, 0.365). The interaction rs5050(T > G)*estradiol was not significant, with EMMs exhibiting overlapping slope confidence intervals across genotypes. The proportion of the variance in angiotensinogen explained by modeling increases from 47.9% to 51.6% when including rs5050(T > G) or interation rs5050(T > G)*estradiol in the model. CONCLUSIONS: rs5050(T > G) is associated with circulating angiotensinogen levels, but rs5050(T > G) alleles do not influence the relationship between estradiol and angiotensinogen. This suggests that estrogen's effect on angiotensinogen regulation occurs independently of rs5050(T > G), despite its location within an estrogen-responsive element.
To elucidate the role of the renin-angiotensin system (RAS) in diabetic nephropathy, we examined the association between diabetic nephropathy in a large cohort of Japanese type 2 diabetic patients and polymorphisms within the genes that encode angiotensin-converting enzyme (ACE), angiotensinogen (AGT) and angiotensin II receptor type 1 (AGTR1). Single nucleotide polymorphisms (SNPs) within these genes were genotyped using invader assay in 747 nephropathy cases and 557 control subjects. Eight SNPs within the ACE gene were significantly associated with diabetic nephropathy (P<0.05), including five SNPs in almost complete linkage disequilibrium to the insertion/deletion polymorphism in the 16th intron (P=0.01, odds ratio =1.34, 95% CI 1.07-1.69). Three SNPs within the AGT, including M235T and one SNP in the AGTR1, were also significantly associated with nephropathy (M235T P=0.01, odds ratio =0.74, 95% CI 0.59-0.94). In addition, we found that the allelic mRNA expression corresponding to the 235M allele was significantly higher than that for the 235T allele in normal kidney tissues. Furthermore, we found a significant additional effect of these three genes by a step-wise logistic regression analysis (final empirical P value =0.00005). We concluded that RAS gene polymorphisms may contribute to the susceptibility to diabetic nephropathy in type 2 diabetes.
BACKGROUND: Genetic variation in the renin-angiotensin system (RAS) has been implicated in stroke, particularly the small vessel disease (SVD) subtype. Furthermore, there may be two distinct subtypes of cerebral SVD, isolated lacunar infarction (ILI) and ischaemic leukoaraiosis (ILA). METHODS: 300 patients with well-phenotyped SVD and 600 controls were genotyped for five polymorphisms in the angiotensinogen (AGT) gene and eight polymorphisms within the angiotensin-converting enzyme (ACE) gene. RESULTS: AGT and ACE polymorphisms and haplotypes were no more common in SVD cases as a whole or the two subtypes. Amongst hypertensives only, an AGT promoter polymorphism (-20A-->C), was associated with the ILA subtype (multivariate odds ratio 1.716, 95% confidence interval 1.073-2.746, p = 0.024). CONCLUSIONS: RAS genetic variants are not strong risk factors for cerebral SVD. The AGT -20C allele may be a risk factor for the leukoaraiosis subtype amongst hypertensives.