Dataset Information

The Association of Haptoglobin Gene Variants and Retinopathy in Type 2 Diabetic Patients: A Meta-Analysis.

ABSTRACT:

Aims/introduction

To collectively evaluate the association between haptoglobin (Hp) gene variants and diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM).

Methods

A comprehensive literature review was performed for eligible studies. After inclusion and exclusion selection as well as quality assessment, those studies meeting quality standards were included. In this study, diabetic patients with retinopathy were selected as the case group and those ones without DR were treated as the control group. The recessive model, allele model, additive model, heterozygote model, and homozygote model were utilized to investigate the association of three Hp gene variants and DR. Subgroup analysis on different severity of DR including nonproliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR) was also conducted.

Results

Six trials from different regions were finally included. A total of 1145 subjects containing 564 T2DM patients with retinopathy were included. The recessive model, allele model, additive model, and homozygote model results showed that Hp gene variants were not associated with DR, NPDR, and PDR. However, the heterozygote model indicated the association of Hp gene variants with DR.

Conclusions

No association was found between the Hp gene variants and PDR and NPDR. More studies are required to verify these findings.

SUBMITTER: Wu H

PROVIDER: S-EPMC5512055 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Publications

The Association of Haptoglobin Gene Variants and Retinopathy in Type 2 Diabetic Patients: A Meta-Analysis.

Wu Huiqun H Wu Huan H Shi Lili L Yuan Xinlu X Yin Ying Y Yuan Mingjie M Zhou Yushan Y Hu Qianwen Q Jiang Kui K Dong Jiancheng J

Journal of diabetes research 20170703

<h4>Aims/introduction</h4>To collectively evaluate the association between haptoglobin (Hp) gene variants and diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM).<h4>Methods</h4>A comprehensive literature review was performed for eligible studies. After inclusion and exclusion selection as well as quality assessment, those studies meeting quality standards were included. In this study, diabetic patients with retinopathy were selected as the case group and those ones withou ...[more]

PMID: 28758129

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Project description:BACKGROUND: Diabetic retinopathy (DR) is classically defined as a microvasculopathy that primarily affects the small blood vessels of the inner retina as a complication of diabetes mellitus (DM).It is a multifactorial disease with a strong genetic component. The aim of this study is to investigate the association of a set of nine candidate genes with the development of diabetic retinopathy in a South Indian cohort who have type 2 diabetes mellitus (T2DM). METHODS: Seven candidate genes (RAGE, PEDF, AKR1B1, EPO, HTRA1, ICAM and HFE) were chosen based on reported association with DR in the literature. Two more, CFH and ARMS2, were chosen based on their roles in biological pathways previously implicated in DR. Fourteen single nucleotide polymorphisms (SNPs) and one dinucleotide repeat polymorphism, previously reported to show association with DR or other related diseases, were genotyped in 345 DR and 356 diabetic patients without retinopathy (DNR). The genes which showed positive association in this screening set were tested further in additional sets of 100 DR and 90 DNR additional patients from the Aravind Eye Hospital. Those which showed association in the secondary screen were subjected to a combined analysis with the 100 DR and 100 DNR subjects previously recruited and genotyped through the Sankara Nethralaya Hospital, India. Genotypes were evaluated using a combination of direct sequencing, TaqMan SNP genotyping, RFLP analysis, and SNaPshot PCR assays. Chi-square and Fisher exact tests were used to analyze the genotype and allele frequencies. RESULTS: Among the nine loci (15 polymorphisms) screened, SNP rs2070600 (G82S) in the RAGE gene, showed significant association with DR (allelic P = 0.016, dominant model P = 0.012), compared to DNR. SNP rs2070600 further showed significant association with DR in the confirmation cohort (P = 0.035, dominant model P = 0.032). Combining the two cohorts gave an allelic P < 0.003 and dominant P = 0.0013). Combined analysis with the Sankara Nethralaya cohort gave an allelic P = 0.0003 and dominant P = 0.00011 with an OR = 0.49 (0.34 - 0.70) for the minor allele. In HTRA1, rs11200638 (G>A), showed marginal significance with DR (P = 0.055) while rs10490924 in LOC387715 gave a P = 0.07. No statistical significance was observed for SNPs in the other 7 genes studied. CONCLUSIONS: This study confirms significant association of one polymorphism only (rs2070600 in RAGE) with DR in an Indian population which had T2DM.

Project description:Diabetic retinopathy (DR) is one of the most severe microvascular complications of diabetes mellitus (DM). The (CA)n microsatellite variation of the aldose reductase (ALR) gene has been indicated to be associated with DR in previous studies; however, the results were inconclusive. To provide a more precise evaluation of the association between the (CA)n variations of ALR and the risk for DR, a meta-analysis was performed in the present study. Relevant articles were retrieved from the PubMed, Embase, Chinese National Knowledge Infrastructure and Cochrane Library databases. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the strength of the associations. The present meta-analysis included 17 studies comprising 1,575 DM patients with retinopathy and 1,741 DM patients without retinopathy. The results indicated that the Z-2 allele was a risk factor for DR in Asian (OR=1.82, 95% CI: 1.16-2.86, P=0.009) and Caucasian (OR=2.08, 95% CI: 1.14-3.79, P=0.02) populations, as well as in type 1 diabetes (T1D; OR=3.42, 95% CI: 1.46-8.04, P=0.005) and type 2 diabetes (T2D; OR=1.66, 95% CI: 1.05-2.63, P=0.03). Furthermore, the Z+2 allele was determined to be a protective factor for DR in Caucasian individuals (OR=0.50, 95% CI: 0.34-0.73, P=0.0004) and those with T1D (OR=0.39, 95% CI: 0.27-0.57, P<0.00001). Z+4 was also identified to be a protective factor, reducing the risk of DR in patients with T1D (OR=0.74, 95% CI: 0.57-0.96, P=0.02). Z-4 was revealed to be a risk factor for DR in Asian populations (OR=1.57, 95% CI: 1.22-2.03, P=0.0005) and in individuals with T1D (OR=1.62, 95% CI: 1.27-2.08, P=0.0001). However, no association was detected between the Z, Z+6 and Z-6 alleles and the risk of DR (P>0.05). In conclusion, the present results revealed the following: Z+2 may serve as a protective factor for DR in Caucasian individuals and those with T1D; Z+4 may be a protective factor for DR in patients with T2D; Z-2 may represent a risk factor for DR in all subgroups analyzed; and Z-4 may be a risk factor for DR in Asian populations and patients with T2D.

Dataset Information

The Association of Haptoglobin Gene Variants and Retinopathy in Type 2 Diabetic Patients: A Meta-Analysis.

Aims/introduction

Methods

Results

Conclusions

Publications

The Association of Haptoglobin Gene Variants and Retinopathy in Type 2 Diabetic Patients: A Meta-Analysis.

Similar Datasets

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