HLA-DRB1*03 as a risk factor for microalbuminuria in same duration of type 1 diabetes: a case control study

Ražanskaitė-Virbickienė, Dovilė; Danytė, Evalda; Žalinkevičius, Rimantas

doi:10.1186/s12882-016-0252-4

Cited by 4 publications

(4 citation statements)

References 25 publications

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“…Rats were housed in separate metabolic cages; 24-h urine was collected and UAE was measured. The DN model was confirmed on obtaining 24-h UAE ≥ 30 mg/24 h (25).…”

Section: Methodsmentioning

confidence: 84%

High Expression of Complement Components in the Kidneys of Type 2 Diabetic Rats With Diabetic Nephropathy

Huang

et al. 2019

Front. Endocrinol.

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Background: Diabetic nephropathy (DN) is the leading cause of end-stage failure of the kidneys; however, its pathogenesis remains unknown. This study assessed the expression of complement components in the kidneys of rats with type 2 DN to investigate their role in DN. Methods: A rat model of type 2 DN was induced by a high-fat diet combined with low-dose streptozotocin. Blood glucose, fasting insulin levels, insulin resistance index, and 24-h urinary albumin excretion (UAE) were measured. Renal tissue morphological features were observed. The mesangial index and arteriosclerosis index were calculated. Immunohistochemistry and western blot were used to measure the expression of complement components in the kidneys. Results: The kidney weight: body weight (mg/g) ratio in the DN group was significantly greater than those in the control and diabetes mellitus (DM) groups. The arteriosclerosis index, mesangial index, and tube area percentage in the DN group were significantly higher than those in the control and DM groups, but these parameters did not significantly differ between the control and DM groups. The expression of the complement components C1q, mannose-binding lectin (MBL), mannan-binding lectin-associated serine protease (MASP)-2, B factor, C3, and C5b-9 in the DN group was significantly higher than that in the control and DM groups but did not significantly differ between the control and DM groups. Most of the complement components were mainly expressed at the renal tubular site. Correlation analysis showed that 24-h UAE were positively correlated with C1q, MBL, MASP-2, B factor, and C5b-9 expression. MI was positively correlated with MBL, B factor, C3, and C5b-9 expression. AI was positively correlated with C1q, MBL, MASP-2, and B factor expression. Conclusion: Complement components including C1q, MBL, MASP-2, B factor, C3, and C5b-9, were highly expressed in the kidneys of type 2 diabetic rats with DN. Most of the complement components were mainly expressed in the renal tubules. High expression of complement components was found to be associated with the progress of DN. Our study suggests that complement system activation is a progressive factor in type 2 diabetic nephropathy. Inhibition of pathological complement activation may be a promising therapeutic strategy for DN.

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“…Rats were housed in separate metabolic cages; 24-h urine was collected and UAE was measured. The DN model was confirmed on obtaining 24-h UAE ≥ 30 mg/24 h (25).…”

Section: Methodsmentioning

confidence: 84%

High Expression of Complement Components in the Kidneys of Type 2 Diabetic Rats With Diabetic Nephropathy

Huang

et al. 2019

Front. Endocrinol.

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“…Some studies have found no relationship between HLA and the risk of diabetic complications 159,160 . Other reports, some of which controlled for disease duration and focusing on the HLA -DR3 and HLA-DR4 allomorphs a priori, have implicated them variably as susceptibility or protective factors in overt DKD or microalbuminuria 161,162,163,164 . In a large, phenome-wide association study (PheWAS), the HLA-DRB1*04 and HLA-DQB1*03:02 alleles, found in the HLA-DR4-HLA-DQ8(3) risk haplotype, were associated with both T1DM itself and DKD 163 .…”

Section: Diabetic Kidney Diseasementioning

confidence: 99%

HLA and kidney disease: from associations to mechanisms

et al. 2018

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Since the first association between HLA and diseases of native kidneys was described almost 50 years ago, technological and conceptual advances in HLA biology and typing, together with better case ascertainment, have led to an improved understanding of HLA associations with a variety of renal diseases. A substantial body of evidence now supports the existence of HLA genetic associations in the field of renal disease beyond the role of HLA in allogeneic responses in transplant recipients. Allomorphs of HLA have emerged as important risk factors in most immune-mediated renal diseases, which, together with other genetic and environmental factors, lead to loss of tolerance and autoimmune-mediated renal inflammation. HLA associations have also been described for renal diseases that are less traditionally seen as autoimmune or immune-mediated. Here, we review essential concepts in HLA biology and the association of HLA with diseases of the native kidneys, and describe the current understanding of the epistatic and mechanistic bases of HLA-associated kidney disease. Greater understanding of the relationship between HLA and kidney function has the potential not only to further the understanding of immune renal disease at a fundamental level but also to lead to the development and application of more effective, specific and less toxic therapies for kidney diseases.

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“…For example, in the study of Chowdhury et al in England, no relationship was reported between diabetic nephropathy and HLA class II (15). Additionally in the study by Ražanskaitė-Virbickienė et al in Lithuania, HLA-DRB1*03 was reported as a risk factor for diabetic nephropathy (P = 0.021) (13) and in the study of Cordovado et al in the United States, HLA-DRB1*04 was introduced as a protective agent against diabetic nephropathy (P = 0.001) (14). Accordingly, in a study conducted by Ma et al in China, the relationship between type 2 diabetes and HLA-DQA1 and HLA-DQB1 was investigated, which showed a significant relationship was reported compared to the healthy subjects (control group) (P < 0.01) (16).…”

Section: Introductionmentioning

confidence: 95%

“…The human leukocyte antigen (HLA) is a group of genes, which has been mostly studied with regard to its association with autoimmune diseases, infections and inflammation. The association of type 1 diabetes and HLA class 2 has been reported in various studies (13,14). However, the number of studies regarding the association of type 2 diabetes and HLA class 2 are scarce.…”

Section: Introductionmentioning

confidence: 99%

Lack of association between diabetic nephropathy and human leukocyte antigen type 2 (HLA II-DQ1) in patients with type 2 diabetes mellitus in west of Iran

et al. 2020

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Introduction: Diabetic nephropathy (diabetic kidney disease) is one of the microvascular complications of diabetes mellitus. The human leukocyte antigen (HLA) is a group of genes that is related to autoimmune diseases, infections and inflammation. Studies regarding the association of type 2diabetes and HLA-II are negligible. Objectives: The aim of this study is to determinate association between diabetic nephropathy and HLA II-DQ1 in diabetes type 2 patients. Patients and Methods: In this study, 120 diabetes type 2 patients were divided into two groups of diabetic nephropathy (case group) and without diabetic nephropathy (control group). Blood samples were taken and DNA was isolated. Asymmetric polymerase chain reaction (PCR) was used to amplify the HLA II-DQ1 exon 2 and exon 3. PCR products were hybridized and labeled with probes on the chip. Determination of HLAII-DQ1 gene typing was conducted by scanning hybrid products and analyzed with PerkinElmer ScanArray software. Results: The results of chi-square test showed no significant difference between expression levels of HLA in the two groups (P<0.05). Conclusion: There was no significant difference between expression levels of HLA in two groups of patients. Various factors such as demographic characteristics, lifestyle, geographic region, and race are the factors influencing the relationship between diabetic nephropathy and DQ1-HLA II. Since this study is conducted in one region and one race and with limited population, it is suggested that future studies should be considered and the association between the mentioned variables with HLA should be considered.

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HLA-DRB1*03 as a risk factor for microalbuminuria in same duration of type 1 diabetes: a case control study

Cited by 4 publications

References 25 publications

High Expression of Complement Components in the Kidneys of Type 2 Diabetic Rats With Diabetic Nephropathy

High Expression of Complement Components in the Kidneys of Type 2 Diabetic Rats With Diabetic Nephropathy

HLA and kidney disease: from associations to mechanisms

Lack of association between diabetic nephropathy and human leukocyte antigen type 2 (HLA II-DQ1) in patients with type 2 diabetes mellitus in west of Iran

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