The M235T polymorphism in the angiotensinogen gene is not a major risk factor for diabetic nephropathy; a meta-analysis

Introduction: Diabetic nephropathy (DN) is the leading cause of chronic kidney disease in diabetes patients. The angiotensin AGT M235T gene polymorphism, which is linked to the renin-angiotensin-aldosterone system (RAAS), has been extensively studied in DN patients, but the results are still conflicting. The current study’s goal is to conduct a meta-analysis to assess the relationship between AGT M235T gene polymorphism and DN susceptibility. Methods: Fourteen case-control studies related to AGT M235T polymorphism and DN were searched using PubMed, Web of Science and Google Scholar databases. Genotype data from the T2DM and T2DN groups were collected from all papers. The pooled odds ratio (OR) and 95 percent confidence interval (95% CI) were calculated employing a random-effects model to assess the relationship. Results: There were no statistically significant link between AGT M235T and DN risk in dominant (P=0.801, OR: 0.95; 95% CI: 0.66-1.38), allelic (P=0.933, OR: 1.01; 95% CI: 0.75-1.37) and recessive (P=0.374, OR: 1.21; 95% CI: 0.80-1.83) genetic models. Further, the stratified analysis based on ethnicity did not reveal significant link between AGT M235T and DN risk in Asian (Dom OR: 1.07; 95% CI: 0.63-1.82) and the Caucasian populations (Dom OR: 0.77; 95% CI: 0.49-1.21). In all three models, there was a high degree of heterogeneity between studies. Publication bias was not seen. Conclusion: Our findings suggest that the AGT gene M235T polymorphism does not contribute to DN risk. However, validation of this association will require multi-center and large population-based studies.

Associations Between M235T Polymorphism in the AGT Gene and Cancer: An Updated Systematic Review and A Meta-analysis

Background: We assessed the relationship between AGT gene M235T polymorphism and the susceptibility to cancer by performing an updated meta-analysis.Methods: This study retrospectively searched related articles in the electronic databases. Afterwards, we determined combined odds ratios (ORs) and related 95% confidence intervals (CIs) by the fixed- or random-effects model.Results: The present meta-analysis enrolled altogether 9 articles. On the whole, the relationship between AGT M235T polymorphism and the cancer risk was not significant among the entire population(TT vs MM:OR=1.28,95%CI=0.80-2.04;TM vs MM: OR=0.90, 95%CI = 0.53-1.52;Recessive model: OR= 1.13, 95%CI = 0.83-1.52; Dominant model: OR=0.93, 95%CI =0.55-1.57). But the relationship of AGT M235T polymorphism with the digestive cancer risk was significant upon subgroup analysis stratified according to cancer type (TT vs MM:OR=1.68,95%CI=1.11-2.54;TM vs MM: OR=1.34, 95%CI = 0.97-1.85;Recessive model: OR= 1.27, 95%CI = 0.95-1.70; Dominant model: OR=1.45, 95%CI =1.07-1.96).Conclusion: According to findings in the present meta-analysis, AGT M235T polymorphism may be possibly related to digestive cancer susceptibility.

Angiotensinogen M235T polymorphism and susceptibility to hypertrophic cardiomyopathy in Asian population: A meta analysis

Objective: To explore the relationship between the polymorphism of angiotensinogen gene (AGT) M235T and susceptibility to hypertrophic cardiomyopathy (HCM) in Asian population by meta-analysis. Methods: PubMed, Embase, Web of Science, Cochrane library, CNKI, Wan Fang, and other databases were searched to collect the literature about AGT M235T polymorphism and HCM from the inception to March 1, 2020. The Newcastle-Ottawa Scale (NOS) checklist was uesd to perform independent literature review and study quality assessment. Data was analyzed by Stata 15.0 software. Results: The results showed that, except for the recessive genetic model (TT vs MT+MM: OR = 1.27, 95%CI: 1.05–1.53), in the other four genetic models, the M235T polymorphism had no significant correlation with the risk of HCM (T vs M: OR = 1.17, 95%CI: 0.88–1.57; TT+MT vs MM: OR = 1.13, 95%CI: 0.55–2.33; TT vs MM: OR = 1.25, 95%CI: 0.60–2.59; TM vs MM: OR = 0.95, 95%CI0.5–1.82). The results of subgroup analysis showed that, except for the heterozygous genetic model, in the other four genetic models, M235T polymorphism was significantly associated with sporadic hypertrophic cardiomyopathy (SHCM), but not with familial hypertrophic cardiomyopathy (FHCM) ( p > 0.05). Conclusion: M235T polymorphism in Asians is associated with HCM, especially SHCM. Heterozygotes increase the risk of patients with SHCM.

P322Inhibitors of the renin-angiotensin system in diabetic patients with heart failure with preserved ejection fraction treatment: impact of m235t polymorphism of angiotensinogen

Background Inhibitors of the renin-angiotensin system plays an important role in chronic heart failure treatment. However, the impact of Angiotensin-converting enzyme (ACE) inhibitors and Angiotensin II receptor blockers (ARBs) on treatment efficacy in diabetic patients with heart failure with preserved preserved ejection fraction (HFpEF) depending on M235T polymorphism of ATG is still unknown. Aim To estimate the efficacy of ACE inhibitors and ARBs therapy in diabetic patient with HFpEF depending on the polymorphism of the M235T of the ATG gene. Methods A total of eighty-two patients (50 females and 32 males; mean age 62,9±8,1 years) with HFpEF and type 2 diabetes mellitus were examined. Sixty-two patients were carriers of 235T allele (MT+TT genotypes), 20 patients had MM genotype of M235T polymorphism of ATG, which was determined by using of polymerase chain reaction. All patients were divided into 4 groups depending on genotypes taking Ramipril or Valsartan during 12 months. Clinical examination, 6 minute walking test, Minnesota Living with Heart Failure Questionnaire (MLHFQ) have been used. All statistical tests were 2-tailed and p<0,05 was considered statistically significant and performed in Statistica 10.0. Results It was not found the significant difference in efficacy of treatment using Valsartan or Ramipril in diabetic patients with genotype MM with HFpEF, whereas in the presence of the T allele of the polymorphism of the M235T ATG, use of valsartan was more effective. Table shows the dynamics of the investigated parameters. Dynamics of parametrs during treatment Parameters HFpEF and DM2T, TT or MT HFpEF and DM2T, MM Ramipril (n=22) Valsartan (n=21) Ramipril (n=10) Valsartan (n=10) Baseline After 12 months treatment Baseline After 12 months treatment Baseline After 12 months treatment Baseline After 12 months treatment SBP, mm Hg 172.0 [157.2; 178.5] 150.0 [132.0; 152.0]* 165.0 [145.3; 174.2] 128.0 [126.0; 134.0]* 167,5 [152.5; 176.0] 140.0 [134.0; 142.0] 160,0 [144.0; 170.0] 146.0 [138.0; 150.0] DBP, mm Hg 98.0 [86.0; 104.0] 92.0 [80.0; 94.0]* 96.0 [82.0; 100.0] 86.0 [80.0; 88.0]* 102.0 [84.0; 106.0] 98.0 [84.0; 100.0] 99.0 [80.0; 100.0] 94.0 [80.0; 96.0] 6 min test, m 313,0 [226,7; 375,5] 320,0 [236,4; 384,6]* 342.5 [258.0; 393.7] 372,0 [262,7; 397,9]* 305.0 [190.5; 375.0] 315.0 [198.5; 384.0] 328.0 [295.0; 401.0] 342.0 [298.0; 410.0] MLHFQ 62,0 [50,0; 71,2] 56,0 [46,5; 68,4]* 61.5 [50.5; 71.5] 40.5 [36.5; 56.5]* 60.0 [47.0; 76.2] 54.0 [43.0; 70.0] 58.0 [49.5; 76.2] 58.0 [49.5; 76.2] Dispnea, % 100 90* 100 70* 100 90 100 80 Edema, % 68,1 54,5* 61,9 33,3* 50 40 60 60 SBP, systolic blood pressure; DBP, diastolic blood pressure; MLHFQ, Minnesota Living with Heart Failure Questionnaire; statistically significant changes (p<0.05). Conclusion Use of Valsartan comparing to Ramipril in diabetic T allele carriers of M235T polymorphism of ATG with HFpEF was independently associated with more effective clinical signs of heart failure improvement, blood pressure decrease, quality of life according to the MLHFQ and physical activity tolerance increase.