Gene polymorphism and plasma levels of miR-155 in diabetic retinopathy

Circulating microRNA-155 (miR-155) is associated with type 2 diabetes mellitus (T2DM) and the rs767649 polymorphism in the pre-MIR155 gene is associated with miR-155 expression. However, their relationship with diabetic retinopathy (DR) is still unknown. Therefore, the aim of this case-control study was to test the hypothesis that the rs767649 polymorphism in the pre-MIR155 gene is associated with DR in South Brazilians with T2DM. We also evaluated the association of plasma levels of miR-155 with DR and the rs767649 polymorphism in a subgroup of subjects. The rs767649 polymorphism was genotyped in 139 blood donors and 546 T2DM patients (244 had no DR, 161 had non-proliferative DR and 141 had proliferative DR). miR-155 expression was quanti fied in 20 blood donors and 60 T2DM patients (20 from each group). Among T2DM patients, the carriership of the A allele and the A allele were more frequent in subjects with DR than in those without it (P < 0.05), and the A allele was independently associated with an increased risk of DR (adjusted OR = 2.12, 95% CI = 1.12–4.01). The plasma levels of miR-155 were lower in T2DM patients than in blood donors (P < 0.001). However, the miR-155 levels did not differ according to the presence and severity of DR or according to rs767649 genotypes among T2DM patients. These findings support that the rs767649 po lymorphism in the pre-MIR155 gene is associated with DR in T2DM and that the miR-155 plasma levels might be associated with T2DM. Additional studies are needed to further investigate their clinical significance in DR and T2DM

Association of polymorphisms in the erythropoietin gene with diabetic retinopathy : a case–control study and systematic review with meta-analysis

Background: Diabetic retinopathy (DR) is characterized by ischemia, hypoxia, and angiogenesis. Erythropoietin (EPO), an angiogenic hormone, is upregulated in DR, and the association of EPO genetic variants with DR is still uncertain, as conflicting results have been reported. Therefore, we performed a case–control study followed by a metaanalysis to investigate whether the rs1617640, rs507392, and rs551238 polymorphisms in EPO gene are associated with DR. Methods: The case–control study included 1042 Southern Brazilians with type 2 diabetes (488 without DR and 554 with DR). Eligible studies for the meta-analysis were searched from electronic databases up to June 1, 2021. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for five genetic inheritance models. Results: The minor alleles of the EPO polymorphisms had nearly the same frequency in all groups of patients (35%), and no association was detected with DR in the case–control study. The meta-analysis included 14 independent sets of cases and controls with 9117 subjects for the rs1617640 polymorphism and nine independent sets with more than 5000 subjects for the rs507392 and rs551238 polymorphisms. The G allele of the rs1617640 polymorphism was suggestively associated with DR under the dominant (OR = 0.82, 95% CI: 0.68–0.98), heterozygous additive (OR = 0.82, 95% CI: 0.69–0.97), and overdominant (OR = 0.88, 95% CI: 0.79–0.97) models. In the subgroup analyses, the G allele was also suggestively associated with proliferative DR (PDR), non-proliferative DR (NPDR), and DR (PDR + NPDR) among patients with type 1 diabetes (T1DM) or non-Asian ancestry. After considering the Bonferroni correction for multiple comparisons, the G allele remained associated with NPDR and DR in T1DM. Regarding the rs507392 and rs551238 polymorphisms, no association was found between these variants and DR. Conclusion: Our findings provide additional support to EPO as a susceptibility gene for DR, with the rs1617640 polymorphism deserving further investigation

Relationship of polymorphisms in the tissue inhibitor of metalloproteinase (TIMP)-1 and -2 genes with chronic heart failure

Dysregulated expression of tissue inhibitors of matrix metalloproteinases (TIMPs) is associated with systolic dysfunction and worsening heart failure (HF). However, no study has assessed the relationship between TIMP polymorphisms and chronic HF. In this study, 300 HF outpatients with reduced left ventricular ejection fraction and 304 healthy blood donors were genotyped for the 372 T > C polymorphism (Phe124Phe; rs4898) in the TIMP-1 gene and the −418 G > C polymorphism (rs8179090) in the TIMP-2 gene to investigate whether these polymorphisms are associated with HF susceptibility and prognosis. The genotype and allele frequencies of the 372 T > C polymorphism in HF patients were not significantly different from those observed among healthy subjects, and the C allele of the −418 G > C polymorphism was very rare in our population (frequency  0.05 for all comparisons). Thus, our findings do not support the hypothesis that the 372 T > C (Phe124Phe) polymorphism in the TIMP-1 gene and the −418 G > C polymorphism in the TIMP-2 gene are associated with HF susceptibility and prognosis in Southern Brazilians

RELAÇÃO DO POLIMORFISMO -1059G>A NO GENE DA METALOPROTEINASE DE MATRIZ-2 (MMP-2) COM A SUSCETIBILIDADE E A MORTALIDADE NA INSUFICIÊNCIA CARDÍACA

A insuficiência cardíaca (IC) é uma síndrome clínica resultante dadeterioração da função cardíaca. Durante a sua progressão, o ventrículo esquerdosofre alterações estruturais na matriz extracelular pela ação das metaloproteinasesde matriz (MMPs). Estudos têm relacionado o aumento da expressão das MMPscom a IC. No presente trabalho, analisamos a associação do polimorfismo -1059GA (rs17859821) no gene da MMP-2 com a presença e progressão da IC. Agenotipagem do polimorfismo -1059GA foi realizada pela técnica de PCR-RFLP. Asfrequências alélicas e genotípicas não diferiram entre os pacientes e os controles (p 0,05) e a análise de sobrevida nos pacientes não indicou nenhuma relação dopolimorfismo -1059GA com a mortalidade total ou por IC (p 0,05)

Association of –1082A&#x3e;G Polymorphism in the Interleukin-10 Gene with Estimated Glomerular Filtration Rate in Type 2 Diabetes

Background/Aims: The -1082A&#x3e;G polymorphism (rs1800896) in the interleukin-10 (IL10) gene has been associated with type 2 diabetes and diabetic retinopathy, but its relationship with diabetic kidney disease (DKD) is uncertain. The aim of this case-control study was to investigate whether the -1082A&#x3e;G polymorphism is associated with DKD in white Brazilians with type 2 diabetes mellitus. Methods: Genotyping was done by real-time polymerase chain reaction for 597 type 2 diabetic outpatients. The definition of DKD was based on estimated glomerular filtration rate (eGFR) and albuminuria, and the patients were grouped in three categories: no DKD (n=249), mild to moderate DKD (n=222), and severe DKD (n=126). Results: The frequency of the minor (G) allele in subjects without DKD did not differ from that observed in subjects with DKD (0.35 vs 0.39, respectively; P = 0.192). Genotype frequencies in subjects without DKD were not significantly different from those observed among patients with mild to moderate DKD or severe DKD. However, considering only the eGFR categories as an indicator of renal function, the AG genotype was independently associated with an increased risk of mildly to moderately decreased eGFR (G3a category) and GG genotype was independently associated with increased risk of kidney failure (G5 category) as compared with AA genotype. Conclusion: Our findings support the hypothesis that the -1082A&#x3e;G polymorphism in the IL10 gene might be associated with DKD in white Brazilians with type 2 diabetes

Relationship of polymorphisms in the tissue inhibitor of metalloproteinase (TIMP)-1 and -2 genes with chronic heart failure

Dysregulated expression of tissue inhibitors of matrix metalloproteinases (TIMPs) is associated with systolic dysfunction and worsening heart failure (HF). However, no study has assessed the relationship between TIMP polymorphisms and chronic HF. In this study, 300 HF outpatients with reduced left ventricular ejection fraction and 304 healthy blood donors were genotyped for the 372 T > C polymorphism (Phe124Phe; rs4898) in the TIMP-1 gene and the −418 G > C polymorphism (rs8179090) in the TIMP-2 gene to investigate whether these polymorphisms are associated with HF susceptibility and prognosis. The genotype and allele frequencies of the 372 T > C polymorphism in HF patients were not significantly different from those observed among healthy subjects, and the C allele of the −418 G > C polymorphism was very rare in our population (frequency  0.05 for all comparisons). Thus, our findings do not support the hypothesis that the 372 T > C (Phe124Phe) polymorphism in the TIMP-1 gene and the −418 G > C polymorphism in the TIMP-2 gene are associated with HF susceptibility and prognosis in Southern Brazilians

Plasma levels of miR-29b and miR-200b in type 2 diabetic retinopathy

MicroRNAs (miRNAs/miRs) are involved in the pathogenesis of diabetes mellitus and its chronic complications, and their circulating levels have emerged as potential biomarkers for the development and progression of diabetes. However, few studies have examined the expression of miRNAs in diabetic retinopathy (DR) in humans. This case-control study aimed to investigate whether the plasma levels of miR-29b and miR-200b are associated with DR in 186 South Brazilians with type 2 diabetes (91 without DR, 46 with non-proliferative DR and 49 with proliferative DR). We also included 20 healthy blood donors to determine the miRNA expression in the general population. Plasma levels of miR-29b and miR-200b were quantified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Proliferative DR was inversely associated with plasma levels of miR-29b (unadjusted OR = 0.694, 95% CI: 0.535-0.900, P = 0.006) and miR-200b (unadjusted OR = 0.797, 95% CI: 0.637-0.997, P = 0.047). However, these associations were lost after controlling for demographic and clinical covariates. In addition, patients with type 2 diabetes had lower miR-200b levels than blood donors. Our findings reinforce the importance of addressing the role of circulating miRNAs, including miR-29 and miR-200b, in DR