scholarly journals Renalase gene Glu37Asp polymorphism affects susceptibility to diabetic retinopathy in type 2 diabetes mellitus

Author(s):  
Monika Buraczynska ◽  
Karolina Gwiazda-Tyndel ◽  
Bartłomiej Drop ◽  
Wojciech Zaluska

Abstract Aims Renalase (RNLS) is an enzyme with monoamine oxidase activity that metabolizes circulating catecholamines. The RNLS gene Asp37Glu missense polymorphism (rs2296545) has been associated with hypertension, cardiac hypertrophy and dysfunction, and stroke. The purpose of our study was to investigate the potential involvement of this polymorphism in the microvascular complications of type 2 diabetes (T2DM). Methods In this case–control study, the polymorphism was genotyped in 860 patients with T2DM and 400 healthy controls. The genotype and allele distribution was compared in subgroups of patients: with diabetic nephropathy (DN+) (n = 405) versus DN− (independently of the presence of DR) and, similarly, patients with diabetic retinopathy (DR+) (n = 328) versus DR− (independently of the presence of DN). Results No significant association was detected between analyzed polymorphism and DN. In contrast, the retinopathy subgroup showed a significantly higher frequency of G allele (OR 1.4, 95% CI 1.16–1.72, p = 0.0005) and GG genotype (OR 1.86, 95% CI 1.26–2.75, p = 0.001) than DR− patients. The effect of RNLS Glu37Asp polymorphism on DR remained significant after adjustments for age, gender, BMI, and duration of T2DM (p = 0.005). Conclusions This is the first study to investigate RNLS gene polymorphism in microvascular complications of T2DM. The results suggest that RNLS rs2296545 SNP might be considered a risk factor for diabetic retinopathy in T2DM patients. This can provide new insight into the role of renalase gene in the pathophysiology of microvascular complications of diabetes.

2016 ◽  
Vol 10 (4) ◽  
pp. 300-308 ◽  
Author(s):  
Elisa Martín-Merino ◽  
Joan Fortuny ◽  
Elena Rivero-Ferrer ◽  
Marcus Lind ◽  
Luis Alberto Garcia-Rodriguez

2020 ◽  
Author(s):  
Shazia Qayyum ◽  
Muhammad Afzal ◽  
Abdul Khaliq Naveed

Abstract Background: The incidence of type 2 diabetes mellitus (T2DM) is rising in working age adults in Pakistan. Diabetic patients have a greater chance for developing diabetic retinopathy (DR). There is negligible research on the genetic factors contributing to DR in Pakistani population. This study was done to investigate the association of vascular endothelial growth factor A gene (VEGFA) polymorphisms, 2578 C/A (rs699947) and 1154 G/A (rs1570360) with T2DM, diabetic retinopathy and serum VEGF levels in Pakistani patients. Methods: A case-control study, conducted from Jan 2017 to Dec 2018, including 450 subjects: 150 DR, 150 diabetics without retinopathy (DWR) and 150 healthy controls (HC). Genotyping was done by ARMS-PCR and serum VEGF levels were measured by ELISA. Descriptive and inferential statistics were calculated to compare genotypic / allelic frequencies and biochemical variables. Results: No statistically significant association of rs699947 and rs1570360 genotypic and allelic frequencies were found with DR as compared to DWR. The rs699947 heterozygosity was associated with DWR and homozygous mutant allele A with DWR and DR as compared to HC. Upon stratifying DR into non- proliferative (NPDR) and proliferative (PDR) sub- types, rs699947 AA genotype was significantly associated with PDR as compared to DWR in univariate and multinomial regression analysis. In allelic, dominant and recessive models, the minor allele A showed significant association with DWR and DR as compared to HC. Significantly raised serum VEGF levels were found in DR patients as compared to DWR and were associated with rs699947 and rs1570360 heterozygosity in DWR. Serum VEGF showed a positive correlation with fasting plasma glucose (FPG), cholesterol and LDL-C in DR and DWR groups. rs699947 genotype showed significant association with DWR and DR in Punjabi and Pathan and with DR in Kashmiri ethnic groups compared to HC. rs1570360 was significantly association with DR as compared to DWR in Kashmiri ethnic group. Conclusion: Our study endorses the role of VEGF 2578C/A (rs699947) gene polymorphism in the pathogenesis of T2DM and proliferative diabetic retinopathy in Pakistani patients. Serum VEGF levels have a positive correlation with T2DM and severity of DR.


2017 ◽  
Vol 51 (3) ◽  
pp. 137-144 ◽  
Author(s):  
ET Zaharieva ◽  
ZA Kamenov ◽  
AS Savov

AbstractObjectives.Compared to type 1 diabetes, the role of the immune and autoimmune pathogenetic mechanisms is much less studied in the type 2 diabetes. Toll-like receptors 4 (TLR4) have a leading role in inflammation, insulin resistance, and vascular damage. This study aimed to analyze the relationship between the polymorphisms inTLR4gene and different stages in the glucose continuum from prediabetes to the type 2 diabetes and chronic microvascular complications.Materials and Methods.The study included 113 patients with the type 2 diabetes, 29 participants with prediabetes, and 28 controls. Polymerase chain reaction (PCR) was used for genotyping Asp299Gly and Thr399Ile polymorphism, followed by restriction analysis.Results.The difference in the genotype frequency for both polymorphisms in patients with the type 2 diabetes or prediabetes compared to that in controls was not significant. Patients with heterozygous genotype of Asp299Gly polymorphism had a higher prevalence of diabetic retinopathy (42.9%) than participants with homozygous genotype (9.0%) (OR [95%CI]=7.61 [1.41–41.08]; p=0.018). No association was established for diabetic polyneuropathy and nephropathy. Prevalence of chronic diabetes complications was not related to Thr399Ile polymorphism.Conclusion.Our study demonstrates that Asp299Gly and Thr399Ile polymorphisms seem not to be associated with the type 2 diabetes and prediabetes but Asp299Gly may contribute to diabetic retinopathy predisposition.


Diabetologia ◽  
2015 ◽  
Vol 58 (7) ◽  
pp. 1443-1447 ◽  
Author(s):  
Alexander D. Miras ◽  
Ling Ling Chuah ◽  
Nofal Khalil ◽  
Alessia Nicotra ◽  
Amoolya Vusirikala ◽  
...  

2016 ◽  
Vol 5 (72) ◽  
pp. 5253-5256
Author(s):  
Subbaiah Vasan Chandrakumar ◽  
Ponnusamy Thiyagarajan ◽  
Amit Jain K ◽  
Thangaraj Murugalakshmi ◽  
Srinivasan Muralikrishnan

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