The relationship between C677T methylenetetrahydrofolate reductase gene polymorphism and retinopathy in type 2 diabetes: a meta-analysis

Ζιντζαράς, Ηλίας; Chatzoulis, Dimitrios Z; Karabatsas, Constantinos H; Stefanidis, Ioannis

doi:10.1007/s10038-005-0250-z

Cited by 76 publications

(60 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…21 A differential magnitude of effect in large versus small studies (or publication bias) for the allele contrast was checked using the Egger regression test for funnel plot asymmetry and the Begg-Mazumdar test, which is based on Kendall's tau. 12,22,23 The main (or overall) analysis included all available data. Subgroup analysis for each racial background was also performed.…”

Section: Selection Of Studiesmentioning

confidence: 99%

See 1 more Smart Citation

Do alcohol-metabolizing enzyme gene polymorphisms increase the risk of alcoholism and alcoholic liver disease?

et al. 2006

Self Cite

View full text Add to dashboard Cite

Case-control studies that have investigated the association between alcoholism and alcoholinduced liver damage and the ADH2, ADH3, CYP2E1, and ADLH2 polymorphisms have reported controversial or inconclusive results. Thus, we conducted a meta-analysis of 50 association studies of the above polymorphisms. We explored potential sources of heterogeneity and bias, performed subgroup analyses by racial background and sex, performed sensitivity analyses for studies not in Hardy-Weinberg equilibrium, and performed a subgroup analysis for cases that met strict criteria for alcoholism. The present meta-analysis underscores significant associations of ADH2*1, ADH3*2, and ALDH2* . When strict criteria were imposed, the pattern of results remained unaltered. For liver disease, there were no significant associations for ADH2*1, ADH3*2, or ALDH2*1 in all subpopulations. The CYP2E1 polymorphism showed no association whatsoever. There is evidence that alleles are mainly dominant. In conclusion, there was heterogeneity between studies in alcoholism for ADH2, ADH3, and ALDH2, and lack of bias in all polymorphisms. The above findings reinforce the need for more rigorous studies, and for regular synthesis of studies' results. O ver the last few years, an increasing number of studies have provided compelling evidence for the involvement of genetically defined predisposing factors in alcoholism and alcohol-induced cirrhosis. The strongest support comes from the fact that not all subjects with a high daily intake of alcohol develop alcohol-induced liver disease. Mostly metabolized in the liver by the successive action of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), the rate of conversion of ingested ethanol to acetaldehyde, and of acetaldehyde to acetate, is influenced by genetic polymorphisms at both loci. ALDH2 is the most important gene that affects predisposition to alcoholism in Asian populations. Thus, the prevalence in these populations of the inactive ALDH enzymatic form encoded by the ALDH2*2 allele appears to protect against alcoholism. 1 Furthermore, alcoholics with this inactive allele may be at great risk for advanced alcoholic liver disease. [2][3][4] Regarding the ADH gene cluster, polymorphisms are also detected at the ADH2 and ADH3 loci with two alleles (referred to as *1 and *2) each. Alleles ADH2*2 and ADH3*1 encode, respectively, for the highly active ␤ 2 and ␥ 1 allozymes, 5 and a low prevalence of both alleles has been reported in alcoholic Asians-although some studies did not detect associations between ADH3 polymor-

show abstract

Section: Selection Of Studiesmentioning

confidence: 99%

“…12 Furthermore, the interpretation is complicated by the fact that different populations, sampling strategies, genotyp- Fig. 1.…”

mentioning

confidence: 99%

Do alcohol-metabolizing enzyme gene polymorphisms increase the risk of alcoholism and alcoholic liver disease?

et al. 2006

Self Cite

View full text Add to dashboard Cite

show abstract

“…Q follows a chi-square distribution with r-1 (r is the number of studies) degrees of freedom (d.f. ), when the ORs were homogeneous (Zintzaras et al 2005). The heterogeneity was considered statistically significant if the P value was <0.10.…”

Section: Data Synthesis and Statistical Analysismentioning

confidence: 99%

“…)/Q), which is independent of the number of studies in the meta-analysis . The I 2 values falls within the range 0-100%, Gao et al (2006) with higher values denoting greater degree of heterogeneity (I 2 = 0-25%, no heterogeneity; I 2 = 25-50%, moderate heterogeneity; I 2 = 50-75%, large heterogeneity; I 2 = 75-100%, extreme heterogeneity) (Zintzaras et al 2005). The Mantel-Haenszel method was used to calculate the fixed-effect pooled ORs (Mantel and Haenszel 1959;Robins et al 1986).…”

Section: Data Synthesis and Statistical Analysismentioning

confidence: 99%

Association of gene polymorphism with genetic susceptibility to stroke in Asian populations: a meta-analysis

2006

View full text Add to dashboard Cite

Stroke is a heterogeneous multifactorial disease and is thought to have a polygenic basis. Casecontrol studies on gene sequence variations have identified a number of potential genetic predisposition factors, but due to the conflicting results, uncertainty remains on the effect of these polymorphisms on risk for the development of stroke. To qualitatively and quantitatively assess the risk associated with different gene polymorphisms for stroke in Asian populations, we comprehensively searched and identified all the studies of association. Clinically overt case-control studies were selected only if neuroimaging had been used as the confirmatory measure for diagnosis of stroke. We performed a meta-analysis of the three most investigated genes, viz., methylenetetrahydrofolate reductase (MTHFR), apolipoprotein E (ApoE) and angiotensinconverting enzyme (ACE). Statistically significant association with stroke were identified for C677T polymorphism of MTHFR [random effects odds ratio (OR) = 1.47, 95% confidence interval (95% CI) 1.19, 1.82; P = 0.0004] and marginally significant association was detected with allele e 4 of ApoE (random effects OR = 1.47, 95% CI 1.00, 2.15; P = 0.049). The sensitivity analysis (exclusion of studies with controls not in HardyWeinberg equilibrium) revealed a significant association of stroke with the MTHFR C677T and ApoE e 4 alleles but showed no association with ACE gene insertion/ deletion polymorphism.

show abstract

“…Various candidate genes have been tested for their association with DR, which includes aldose reductase, 12,13 nitric oxide synthase, 14,15 and MethylTetra Hydro Folate Reductase 16 that have had conflicting reports in various populations. Among many candidate genes that have been found to be associated with retinopathy, the gene encoding RAGE is of particular significance, because the RAGE-mediated signaling induces key pathological changes in the microvasculature leading to DR. A functional polymorphism Gly82Ser in exon 3 has been previously implicated in DR of which the Ser allele of this Gly82Ser polymorphism has been shown to be protective in the development of DR in the Asian-Indian population.…”

Section: Introductionmentioning

confidence: 99%

Rage gene promoter polymorphisms and diabetic retinopathy in a clinic-based population from South India

Ramprasad

Radha

Mathias

et al. 2006

Eye

View full text Add to dashboard Cite

Purpose The main objective of this study was to evaluate if the À429T/C, À374T/A and 63 bp deletion polymorphisms in the RAGE gene are associated with diabetic retinopathy (DR) among Type 2 diabetic subjects in a clinicbased population from South India. Methods We screened 149 normal glucose tolerant subjects (NGT), 189 Type 2 diabetes subjects without retinopathy (DM) and 190 subjects with DR for these polymorphisms using the PCR-RFLP method. DR was diagnosed by grading color fundus photography. Logistic regression models were used to evaluate the association of individual polymorphisms with DR. Expectationmaximization algorithms were implemented in haplotype tests of association to examine the combined effects of À429T/C and À374T/A polymorphisms on DR. Results The allelic frequencies of À429T are 0.83 in NGT, 0.84 in DM and 0.85 in DR subjects, and that of À374T are 0.93 in NGT, 0.92 in DM and 0.88 in DR subjects. The À374 polymorphism was found to be associated with non-proliferative retinopathy when this subgroup was compared to the DM group (OR ¼ 1.814, 95% CI ¼ 1.005-3.273). However, this association was not obvious when both the subphenotypes of DR (the nonproliferative and proliferative DR groups) were studied jointly. We found no evidence for associations between the À429T/C polymorphism and the DR phenotype. Finally, extension to a 2-SNP haplotype did not reveal any significant statistical difference between the groups (P ¼ 0.668).

show abstract

The relationship between C677T methylenetetrahydrofolate reductase gene polymorphism and retinopathy in type 2 diabetes: a meta-analysis

Cited by 76 publications

References 54 publications

Do alcohol-metabolizing enzyme gene polymorphisms increase the risk of alcoholism and alcoholic liver disease?

Do alcohol-metabolizing enzyme gene polymorphisms increase the risk of alcoholism and alcoholic liver disease?

Association of gene polymorphism with genetic susceptibility to stroke in Asian populations: a meta-analysis

Rage gene promoter polymorphisms and diabetic retinopathy in a clinic-based population from South India

Contact Info

Product

Resources

About