Renan Cesar Sbruzzi

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 < 1%). After a median follow-up duration of 5.5 years, 121 patients (40.3%) died (67 of them from HF). Survival analysis did not show statistically significant differences in all-cause death and HF-related death between patients with and without the T allele (P > 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.

Interleukin-10 -1082A>G (rs1800896) polymorphism is associated with diabetic retinopathy in type 2 diabetes

AIM To investigate whether the -1082A > G polymorphism (rs1800896) in the interleukin-10 (IL10) gene is associated with diabetic retinopathy (DR) in Brazilians with type 2 diabetes mellitus. METHODS This case-control study included 847 outpatients with type 2 diabetes and 145 healthy blood donors. Four hundred and two patients had no DR, 253 had non-proliferative DR (NPDR), and 192 had proliferative DR (PDR). Genotyping was done by real-time PCR. RESULTS Genotype and allele frequencies were similar in patients and blood donors. In relation to the presence and severity of DR, the AA genotype was overrepresented among patients with NPDR, whereas the GG genotype was more frequent among patients with PDR. Multiple logistic regression analysis showed that the AA genotype was independently associated with increased risk of NPDR, after controlling for duration of diabetes, body mass index, and insulin use (adjusted OR = 1.50; 95% CI = 1.04-2.17). The GG genotype, however, did not remain associated with increased risk of PDR (adjusted OR = 1.49; 95% CI = 0.78-2.86). CONCLUSIONS This study identified, for the first time, an independent association of the -1082A > G polymorphism in the IL10 gene with NPDR in type 2 diabetes. This finding provides additional evidence supporting that genetic variants of IL10 are involved in the pathogenesis of DR.

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

Background/Aims: The -1082A>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>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>G polymorphism in the IL10 gene might be associated with DKD in white Brazilians with type 2 diabetes.

Relationship of polymorphisms in microRNAs -124 e -126 with diabetic retinopathy in patients with type 2 diabetes.

Background MicroRNAs (miRs) are small non-coding molecules that regulate gene expression post-transcriptionally by promoting translational repression or degradation of target mRNAs. Altered expression as well as mutations in the sequences of miRs or their target sites have been related to a great number of diseases, including diabetes and its complications. The G allele of the rs531564 (C>G) polymorphism in miR-124 gene was already associated with increased risk of type 2 diabetes mellitus (T2D) and the A allele of the rs4636297 (G>A) polymorphism of miR-126 gene was associated with severity of diabetic retinopathy (DR).