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Elias Zintzaras

Publications and source records attributed to Elias Zintzaras.

At least 19 recordsLinked to original sources
PubMed2007

Meta-analysis of genome-wide scans provides evidence for sex- and site-specific regulation of bone mass.

UNLABELLED: Several genome-wide scans have been performed to detect loci that regulate BMD, but these have yielded inconsistent results, with limited replication of linkage peaks in different studies. In an effort to improve statistical power for detection of these loci, we performed a meta-analysis of genome-wide scans in which spine or hip BMD were studied. Evidence was gained to suggest that several chromosomal loci regulate BMD in a site-specific and sex-specific manner. INTRODUCTION: BMD is a heritable trait and an important predictor of osteoporotic fracture risk. Several genome-wide scans have been performed in an attempt to detect loci that regulate BMD, but there has been limited replication of linkage peaks between studies. In an attempt to resolve these inconsistencies, we conducted a collaborative meta-analysis of genome-wide linkage scans in which femoral neck BMD (FN-BMD) or lumbar spine BMD (LS-BMD) had been studied. MATERIALS AND METHODS: Data were accumulated from nine genome-wide scans involving 11,842 subjects. Data were analyzed separately for LS-BMD and FN-BMD and by sex. For each study, genomic bins of 30 cM were defined and ranked according to the maximum LOD score they contained. While various densitometers were used in different studies, the ranking approach that we used means that the results are not confounded by the fact that different measurement devices were used. Significance for high average rank and heterogeneity was obtained through Monte Carlo testing. RESULTS: For LS-BMD, the quantitative trait locus (QTL) with greatest significance was on chromosome 1p13.3-q23.3 (p = 0.004), but this exhibited high heterogeneity and the effect was specific for women. Other significant LS-BMD QTLs were on chromosomes 12q24.31-qter, 3p25.3-p22.1, 11p12-q13.3, and 1q32-q42.3, including one on 18p11-q12.3 that had not been detected by individual studies. For FN-BMD, the strongest QTL was on chromosome 9q31.1-q33.3 (p = 0.002). Other significant QTLs were identified on chromosomes 17p12-q21.33, 14q13.1-q24.1, 9q21.32-q31.1, and 5q14.3-q23.2. There was no correlation in average ranks of bins between men and women and the loci that regulated BMD in men and women and at different sites were largely distinct. CONCLUSIONS: This large-scale meta-analysis provided evidence for replication of several QTLs identified in previous studies and also identified a QTL on chromosome 18p11-q12.3, which had not been detected by individual studies. However, despite the large sample size, none of the individual loci identified reached genome-wide significance.

Bone Density↗
PubMed2006

Identification of chromosomal regions linked to premature myocardial infarction: a meta-analysis of whole-genome searches.

Myocardial infarction (MI) is a complication of coronary artery disease and the leading cause of death in the Western world. MI is considered a distinct phenotype with an increased genetic component for its premature type. MI's exact inheritance pattern is still unknown. Genome searches for identifying susceptibility loci for premature MI produced inconclusive or inconsistent results. Thus, a genome search meta-analysis (GSMA) was applied to available genome search data on premature MI. GSMA is a non-parametric method to identify genetic regions that rank high, on average in terms of linkage statistics across genome searches unweighted or weighted by study size. The significance of each region's average and heterogeneity, unadjusted or adjusted by neighbouring average simulated ranks, was calculated using a Monte Carlo test. The meta-analysis involved five genome searches in Caucasians. Eight regions (6p22.3-6p21.1, 14p13-14q13.1, 13q33.1-13q34, 5p15.33-5p15.1, 8q13.2-8q22.2, 1p36.21-1p35.2, 12q24.31-12q24.33, 8q24.21-8q24.3) were found to have significant average rank by either unweighted or weighted analyses. In addition, region 8q24.21-8q24.3 produced significant low heterogeneity (P (unadjusted)=0.03 and P (adjusted)=0.05). Four regions (6p22.3-6p21.1, 14p13-14q13.1, 8q13.2-8q22.2, 8q24.21-8q24.3) were not identified by the individual studies. The meta-analysis suggests that these four regions should be further investigated for genes that confer susceptibility to MI.

Adult↗
PubMed2006

Endothelial NO synthase gene polymorphisms and hypertension: a meta-analysis.

Studies investigated the association between endothelial NO synthase gene polymorphisms and hypertension-reported contradicted or nonconclusive results. A meta-analysis of 35 genetic association studies that examined the relation between hypertension and the G894T, 4a/b, T786C, and G23T polymorphisms of the endothelial nitric oxide synthase gene was carried out. Subgroup analysis by ethnicity and potential sources of heterogeneity and bias were explored. The meta-analysis included genotype data on 7779/10 498, 2216/3222, 2491/3913, and 833/587 cases/controls for G894T, 4b/a, T786C, and G23T, respectively. For the 4b/a polymorphism, overall, the heterogeneity between studies was not significant (P=0.82), and the allele b was associated with a 15% decreased risk of hypertension relative to allele a (odds ratio: 0.85; 95% CI: 0.74 to 0.98). Overall and in whites, the recessive model for allele b produced significant results (odds ratios: 0.78; 95% CI: 0.68 to 0.90 and OR: 0.76 95% CI: 0.62 to 0.92, respectively), whereas the dominant model produced nonsignificant results. In studies involved East Asians and blacks, an association was not demonstrated. Regarding the G894T, T768C, and G23T polymorphisms, in no case (ie, overall, in whites, or in East Asians) was a statistically significant association and heterogeneity found. There was no substantial source of bias in the selected studies. In conclusion, there is evidence of association only between 4b/a polymorphism and hypertension; however, studies exploring combinations of the polymorphisms may help us better understand the genetics of hypertension.

Humans↗
PubMed2006

A meta-analysis of genotypes and haplotypes of methylenetetrahydrofolate reductase gene polymorphisms in acute lymphoblastic leukemia.

A meta-analysis of case-control studies that investigated the association between the C677T and/or A1298C polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene and acute lymphoblastic leukemia (ALL) was carried out. Pooled odds ratios (OR) of various genetic contrasts of each polymorphism were estimated using random (RE) and fixed effects (FE) models. Pooled ORs for combined genotypes and haplotypes were estimated after adjustment for study effect using a log-linear model and the expectation-maximization algorithm in combination with log-linear modeling, respectively. The recessive model for allele 1298C produced a rather marginal association: RE OR: 0.67; 95% confidence interval (CI): 0.46-0.99 and FE OR: 0.64; 95% CI: 0.49-0.84. In Caucasians, the results of the recessive model for allele 1298C was consisted with a protective effect of ALL development: FE OR: 0.63; 95% CI: 0.46-0.87. In childhood ALL, according to the results of the allele contrast and the recessive model for 677T allele it was conceivable that a protective effect exist: RE OR = 0.74; 95% CI: 0.57-0.96 and RE OR: 0.69; 95% CI: 0.51-0.94, respectively. The combined genotypes produced significant pooled OR for the 677CC/1298CC relative to 677CC/1298AA (OR: 0.54; 95% CI: 0.36-0.80). The haplotype 677C/1298C might be more protective to ALL relative to haplotype 677C/1298A (OR: 0.77; 95% CI: 0.61-0.97). When studies not in Hardy-Weinberg equilibrium (HWE) were corrected to account for departures from HWE, then, the pattern of results remained the same. Overall, there is high heterogeneity between the studies in both polymorphisms. A differential magnitude of effect in large versus small studies and alteration of early extremes effects existed.

Adolescent↗
PubMed2006

A tree-based decision rule for identifying profile groups of cases without predefined classes: application in diffuse large B-cell lymphomas.

In this paper, we examined the utility of a forward growing classification tree as a supplement to cluster analysis for deriving a decision rule for the identification of profile groups when the cases do not belong to predefined classes. The technique was applied for the identification of low and high proliferation profile groups of diffuse large B-cell lymphomas according to the immunohistochemical expression levels of proliferation proteins. In a forward growing classification tree method, the size of the tree is controlled by the improvement (threshold value) in the apparent misclassification rate after each split. The classes used in the tree were defined using k-means clustering. The decision rule consisted of the splitting points of the split variables used. The methodology was applied to the histology data from 79 cases of diffuse large B-cell lymphomas. Ten classes of individual cases were derived from k-means clustering. Then, a classification tree with a threshold of 2% was used to derive the decision rule. Branches at the left side of the tree consisted of individuals with a low proliferation profile and branches at the right side of the tree consisted of cases with a high proliferation profile. The classification tree, as a supplement method, not only identified but also provided decision rules for identifying profile groups. Finally, it also allowed for exploration of the data structure.

Algorithms↗
PubMed2006

Extreme between-study homogeneity in meta-analyses could offer useful insights.

OBJECTIVES: Meta-analyses are routinely evaluated for the presence of large between-study heterogeneity. We examined whether it is also important to probe whether there is extreme between-study homogeneity. STUDY DESIGN: We used heterogeneity tests with left-sided statistical significance for inference and developed a Monte Carlo simulation test for testing extreme homogeneity in risk ratios across studies, using the empiric distribution of the summary risk ratio and heterogeneity statistic. A left-sided P=0.01 threshold was set for claiming extreme homogeneity to minimize type I error. RESULTS: Among 11,803 meta-analyses with binary contrasts from the Cochrane Library, 143 (1.21%) had left-sided P-value <0.01 for the asymptotic Q statistic and 1,004 (8.50%) had left-sided P-value <0.10. The frequency of extreme between-study homogeneity did not depend on the number of studies in the meta-analyses. We identified examples where extreme between-study homogeneity (left-sided P-value <0.01) could result from various possibilities beyond chance. These included inappropriate statistical inference (asymptotic vs. Monte Carlo), use of a specific effect metric, correlated data or stratification using strong predictors of outcome, and biases and potential fraud. CONCLUSION: Extreme between-study homogeneity may provide useful insights about a meta-analysis and its constituent studies.

Databases, Bibliographic↗
PubMed2006

Heterogeneity-based genome search meta-analysis for preeclampsia.

Preeclampsia is a pregnancy-related disorder that causes maternal and fetal morbidity and mortality. Its exact inheritance pattern is still unknown, and genome searches for identifying susceptibility loci for preeclampsia have thus far produced inconclusive or inconsistent results. We performed a heterogeneity-based genome search meta-analysis (HEGESMA) that synthesized the available genome scan data on preeclampsia. HEGESMA identifies genetic regions (bins) that rank highly on average in terms of linkage statistics across genome scans (searches). The significance of each bin's average rank and heterogeneity across scans was calculated using Monte Carlo tests. The meta-analysis involved four genome-scans on general preeclampsia and five scans on severe preeclampsia. In general preeclampsia, 13 bins had significantly high average rank (Prank< 0.05) by either unweighted or weighted analyses, while four of them (2p11.2-2q21.1, 9q21.32-9q31.2, 2p15-2p11.2, 2q32.1-2q35) were formally significant by both analyses. Heterogeneity of bin 2.8 (2q32.1-2q35) was significantly low in both unweighted and weighted analysis (PQ< 0.01). In severe preeclampsia, 10 bins had significantly high average rank by either unweighted or weighted analyses and five of them (3q11.1-3q21.2, 2q37.1-2q37.3, 18p11.32-18p11.22, 2p15-2p11.2, 7q34-7q36.3) were significant by both analyses. Bin 2q37.1-2q37.3 showed marginal low heterogeneity in unweighted and weighted analysis (PQ= 0.06). Results should be interpreted with caution as the p values were modest. Further investigation of these regions by genotyping with additional markers and families may help to direct the identification of candidate genes for preeclampsia.

Chromosome Mapping↗
PubMed2006

Association of methylenetetrahydrofolate reductase (MTHFR) polymorphisms with genetic susceptibility to gastric cancer: a meta-analysis.

To clarify the influence of MTHFR C677T and A1298C polymorphisms on gastric cancer (GC), a meta-analysis of eight case-control studies (1,584/2,785 cases/controls) was carried out. Overall, there was moderate heterogeneity among studies, and the C677T allele T was associated with a 27% increased risk of GC compared with C allele: the random effects (RE) OR (95% confidence interval in parenthesis) was significant [OR=1.27 (1.13-1.44)]. In East Asians, the association was significant: RE OR=1.28 (1.14-1.44), whereas, in Caucasians it was not significant. Regarding gastric cancer adenocarcinoma (GCA), an association for the allele contrast in East Asians was detected: fixed effects (FE) OR=1.36 (1.18-1.56). The recessive model for allele T produced significant results overall and in East Asians for GC [FE OR=1.47 (1.26-1.72) and FE OR=1.61 (1.32-1.96), respectively] and for GCA [RE OR=1.53 (1.13-2.05) and FE OR=1.70 (1.36-2.12)]. The A1298C polymorphism was associated with GCA in East Asians: the FE OR for the allele contrast (C vs. A) was 1.38 (1.18-1.62), and under a recessive model for allele C, OR=1.62 (1.28-2.06). There were no sources of bias in the selected studies; the differential magnitude of effect in large versus small studies was not significant. In conclusion, there is evidence of association between MTHFR polymorphisms and GC, mainly in East Asians.

Adenocarcinoma↗
PubMed2006

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

Case-control studies that have investigated the association between alcoholism and alcohol-induced 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*1 alleles and the risk of alcoholism (OR = 1.89 [95% CI 1.56-2.28], 1.32 [95% CI 1.12-1.57], and 4.35 [95% CI 3.04-6.23], respectively). The subsequent subgroup analyses showed association for ADH2*1 and ADH3*2 only in East Asians (OR = 2.23 [95% CI 1.81-2.74] and 1.91 [95% CI 1.45-2.53], respectively) and East Asian males (OR = 2.21 [95% CI 1.57-3.10], 1.69 [95% CI 1.10-2.59], respectively). In East Asian males, the OR for ALDH2*1 was 3.66 (95% CI 1.68-7.96). In Caucasians, sensitivity analysis revealed an association for ADH2*1 in alcoholism (OR = 1.62 [95% CI 1.22-1.89]). 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.

Alcohol Dehydrogenase↗
PubMed2006

Association between primary nocturnal enuresis and habitual snoring in children.

OBJECTIVES: Nocturnal enuresis has been associated with obstructive sleep-disordered breathing mostly in hospital-referred adults and children. To investigate whether primary nocturnal enuresis is significantly associated with habitual snoring in the general pediatric population irrespective of subjects' age and sex, we studied children attending six randomly selected schools in a city in central Greece. METHODS: A questionnaire regarding the symptoms of sleep-disordered breathing and the presence of nocturnal enuresis (bedwetting for at least one night per week) was answered by the children's parents. RESULTS: A total of 1821 children (age 5 to 14 years; 896 girls) were included in the study. Of these, 135 (7.4%) were snoring more frequently than three nights per week (habitual snorers). The habitual snorers had a history of primary nocturnal enuresis more often than did nonhabitual snorers (7.4% versus 2%; odds ratio 4.00, 95% confidence interval 1.93 to 8.32). The association of primary nocturnal enuresis with habitual snoring remained significant after adjustment for age and sex (odds ratio 3.54, 95% confidence interval 1.68 to 7.44). CONCLUSIONS: In a community sample of children, those with habitual snoring more often had primary nocturnal enuresis than did those without snoring.

Adolescent↗
PubMed2006

C677T and A1298C methylenetetrahydrofolate reductase gene polymorphisms in schizophrenia, bipolar disorder and depression: a meta-analysis of genetic association studies.

A meta-analysis of the previous studies of allelic association between schizophrenia, bipolar disorder and depression with the C677T and A1298C polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene was carried out. Attention was paid to genetic differences in ancestral groups. Ten studies of the C677T MTHFR polymorphism and schizophrenia were included, along with four studies with the A1298C MTHFR polymorphism and schizophrenia. Four association studies of the C677T MTHFR polymorphism with bipolar disorder, and five studies of the C677T base pair change with depression were included. The studies contained Caucasian and east Asian samples. For schizophrenia, the main analysis for investigating the association of the C677T allele T and the risk of developing schizophrenia relative to the allele C showed lack of heterogeneity (P = 0.22, I(2) = 24%) between samples. In these samples, the fixed effects odds ratio was marginally significant [odds ratio 1.13 (95% confidence interval, 1.04-1.23)]. In an analysis of subgroups, the odds ratio were not significant for the Caucasian sample [random effects odds ratio 1.14 (0.95-1.36) and fixed effects odds ratio 1.13 (1.00-1.27)](P = 0.14, I(2) = 43%) and in Asians [random effects odds ratio 1.15 (0.98-1.35) and fixed effects odds ratio 1.15 (1.01-1.31)] (P = 0.19, I(2) = 37). The recessive model for allele T produced significant results in the main analysis [fixed effects odds ratio 1.32 (1.12-1.56)] in east Asians [fixed effects odds ratio 1.45 (1.13-1.85)] and female participants [fixed effects odds ratio 1.70 (1.07-2.71)], whereas for Caucasians the results were nonsignificant. For the A1298C polymorphism, in the main analysis the allele frequency difference between C and A, and the dominant model for allele C produced marginally significant associations [fixed effects odds ratio 1.16 (1.03-1.31) and fixed effects odds ratio 1.19 (1.02-1.40), respectively]. In bipolar disorder, overall, there was no significant association between either allele of the C677T polymorphism and the risk of developing bipolar disorder. Only in the east Asian population was the C677T association of marginal significance, with fixed effects odds ratio 1.23 (1.00-1.52). No sources of potential bias were found in the selected studies. The meta-analysis results suggested that east Asians have a greater genetic risk from the MTHFR gene in developing schizophrenia and depression, and that the genetic effects in bipolar disorder and depression are different. A further exploration of the involvement of the MTHFR gene in the susceptibility to schizophrenia and affective disorders, with a greater number of studies with larger sample sizes, however, are needed to fully establish the role of the MTHFR gene.

Bipolar Disorder↗
PubMed2006

Performance of antibodies against tissue transglutaminase for the diagnosis of celiac disease: meta-analysis.

A meta-analysis of studies investigating the diagnostic accuracy of enzyme-linked immunosorbent assays (ELISA) for antibodies against tissue transglutaminases (tTG) of various origins in celiac disease (CD) diagnosis was carried out. Twenty-one studies, with untreated CD patients and healthy/CD-free controls, were included in the meta-analysis. The diagnostic accuracy was estimated using a summary receiver operating characteristic (SROC) curve and pooled sensitivity (Se) and specificity (Sp). Multiple assays within a study were treated by considering all the assays within a study and by analyzing the most popular assay (i.e., the commercial anti-tTTG ELISA most frequently utilized in the papers in which multiple assays were included). The SROC curve indicated the absence of heterogeneity, and the superiority of recombinant human tTG (rh-tTG) and purified human tTG (ph-tTG) compared to guinea pig-tTG (gp-tTG). The sensitivities (most popular assay) for rh-tTG, ph-tTG, and gp-tTG were 94%, 90%, and 92%, respectively, and the specificities were 97%, 92%, and 96%, respectively. A sensitivity analysis (exclusion of studies with bias) altered the results of ph-tTG: Se, 95%; Sp, 98%. The sensitivities (all individual assays) for rh-tTG, ph-tTG, and gp-tTG were 94%, 94%, and 91%, respectively, and the specificities were 95%, 94%, and 89%, respectively. Human tTG ELISA is sensitive and specific, and it can be used for mass screening. Sensitivity analysis showed that ph-tTG might perform better.

Animals↗
PubMed2005

The risk of lymphoma development in autoimmune diseases: a meta-analysis.

BACKGROUND: The risk of development of non-Hodgkin lymphoma (NHL) in autoimmune patients has been investigated in several cohort studies. These studies revealed inconclusive results. To shed some light on this controversy, we conducted a meta-analysis of all available cohort studies linking systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and primary Sjögren syndrome (pSS) to the risk of NHL development. METHODS: We searched the PubMed database (1974 to April 2005) for English-language cohort studies using the key words systemic lupus erythematosus, SLE, rheumatoid arthritis, RA, Sjögren syndrome, or SS; non-Hodgkin lymphoma; and relative risk, RR, standardized incidence rate, or SIR. All cohort studies that used established diagnostic criteria for SLE, RA, and pSS; had histologic confirmation of NHL; and provided standardized incidence rates (SIRs) were included in the meta-analysis. RESULTS: The 20 studies chosen for the analysis included 6 for SLE, 9 for RA, and 5 for pSS. Overall, the meta-analysis suggested extreme heterogeneity among the studies (P < .01; I2 > 70%), high risk of NHL development for pSS (random effects SIR, 18.8; 95% confidence interval [CI], 9.5-37.3); moderate risk for SLE (random effects SIR, 7.4; 95% CI, 3.3-17.0); and lower risk for RA (random effects SIR, 3.9; 95% CI, 2.5-5.9). In RA, the random effects SIRs of NHL with conventional antirheumatic treatment, cytotoxic treatment, and treatment with a biological agent were 2.5 (95% CI, 0.7-9.0), 5.1 (95% CI, 0.9-28.6), and 11.5 (95% CI, 3.7-26.9), respectively. CONCLUSIONS: Rheumatic disease may present a potential risk factor for development of NHL. In this regard, we focused on the underlying pathophysiologic mechanisms related to lymphomagenesis in pSS, SLE, and RA, to justify the varying potential for and background of NHL development.

Antirheumatic Agents↗
PubMed2005

The role of G196A polymorphism in the brain-derived neurotrophic factor gene in the cause of Parkinson's disease: a meta-analysis.

The association between Parkinson's disease (PD) and the G196A polymorphism in the brain-derived neurotrophic factor (BDNF) gene has been investigated in several case-control studies, producing contradictory results: one study indicated that homozygocity of AA is associated with PD, another study produced the opposite result, whereas other studies found no association. To investigate these contradictory findings, a meta-analysis of all available association studies between the G196A polymorphism and the risk of developing PD was conducted. Four out of six identified studies included populations of East Asian descent, and two included populations of European descent (Whites). Overall, the meta-analysis of the allele contrast (A vs G) suggested large heterogeneity between studies (P=0.07, I2 =51%) and no association between G196A and the risk of developing PD: random effects odds ratio (OR)=1.00 [95% CI (0.85, 1.18)]. The sensitivity analysis (exclusion of two studies: one East Asian and one White) with the controls not in Hardy-Weinberg equilibrium showed large heterogeneity (P=0.10, I2 =52%) and no significant association: random effects OR=0.94 [95% CI (0.77, 1.15)]. The subgroup analyses for East Asians and Whites produced no significant association. In addition, the contrast of homozygotes, and the dominant and recessive models for allele A did not support a major role for this polymorphism in the pathogenesis of PD. There were no sources of bias in the selected studies, and the differential magnitude of effect in large vs small studies was not significant. The meta-analysis results suggest that the involvement of the BDNF gene in susceptibility to PD merits further exploration with larger and more rigorous population association studies.

Asian People↗
PubMed2005

HEGESMA: genome search meta-analysis and heterogeneity testing.

SUMMARY: Heterogeneity and genome search meta-analysis (HEGESMA) is a comprehensive software for performing genome scan meta-analysis, a quantitative method to identify genetic regions (bins) with consistently increased linkage score across multiple genome scans, and for testing the heterogeneity of the results of each bin across scans. The program provides as an output the average of ranks and three heterogeneity statistics, as well as corresponding significance levels. Statistical inferences are based on Monte Carlo permutation tests. The program allows both unweighted and weighted analysis, with the weights for each study as specified by the user. Furthermore, the program performs heterogeneity analyses restricted to the bins with similar average ranks. AVAILABILITY: http://biomath.med.uth.gr.

Chromosome Mapping↗
PubMed2005

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

The association between retinopathy in type 2 diabetes [diabetic retinopathy (DR)] and the C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene has been investigated in several case-control studies. These studies rendered contradictory results, some indicating that the polymorphism is associated with the risk of developing DR whereas others concluded there is no association. To shed light on these inconclusive findings, a meta-analysis of all available studies relating the C677T polymorphism to the risk of developing DR was conducted. Four out of five identified studies included populations of East Asian descent, and only one involved samples from European descent (Caucasians). Overall, the meta-analysis suggested large heterogeneity between studies (p = 0.08, I(2) = 52%) and marginal association between C677T transition and the risk of developing DR: random effects odds ratio (OR) = 1.39 [95% CI (1.05, 1.83)]. The sensitivity analysis [exclusion of one East Asian study with the controls not in Hardy-Weinberg equilibrium (HWE)] showed no heterogeneity (p = 0.25, I(2) = 27%) and no significant association: fixed effects OR = 1.22 [95% CI (0.99, 1.51)] and random effects OR = 1.24 [95% CI (0.96, 1.60)]. The sub-group analysis for the East Asian population produced a significant association: fixed effects OR = 1.48 [95% CI (1.20, 1.83)] and random effects OR = 1.52 [95% CI (1.14, 2.03)]. However, sensitivity analysis in East Asians revealed that the association is marginal: fixed effects OR = 1.33 [95% CI (1.04, 1.70)] and random effects OR = 1.36 [95% CI (1.01, 1.83)]. There is a source of bias in the selected studies: the largest studies failed to show association while the smallest study claimed an association. The above findings reinforce the need for larger and more rigourous studies in this area.

Diabetes Mellitus, Type 2↗
PubMed2005

Association between the GLUT1 gene polymorphism and the risk of diabetic nephropathy: a meta-analysis.

The association between diabetic nephropathy (DN) and the XbalphaI polymorphism in the GLUT1 gene has been investigated in several case-control studies. These studies rendered contradictory results: the allele XbalphaI(-) was shown either to be a risk factor or neutral, or even protective for the development of the disease. To shed some light on these inconclusive findings, a meta-analysis of all available studies relating the XbalphaI polymorphism to the risk of developing DN was conducted. Five out of six identified studies included Caucasian populations, and only one involved samples from an Asian population. Overall, the meta-analysis suggested large heterogeneity between studies (P<0.01, I2=68%) and lack of association between allele XbalphaI(-) and the risk of developing DN relative to allele XbalphaI(+): random effects odds ratio (OR)=1.26 [95% CI (0.93, 1.69)]. Excluding one study with the controls not in Hardy-Weinberg equilibrium, the sensitivity analysis revealed that heterogeneity (P=0.28, I2=21%) could be explained, and then, there is an overall association: fixed effects OR=1.34 [95% CI (1.13, 1.60)]. Then, significant ORs were also found on analysis of subgroups: for the Caucasian population, fixed effects OR=1.29 [95% CI (1.08, 1.56)] and for the type 2 diabetic patients fixed effects OR=1.69 [95% CI (1.09, 2.63)]. In type 1 diabetes, there is a moderate heterogeneity (P=0.19, I2=41%) with fixed effects OR=1.29 [95% CI (1.06, 1.56)] and random effects OR=1.32 [95% CI (1.01, 1.71)]. There is a source of bias in the selected studies: large studies failed to show association while small studies claimed an association. Although there is evidence of association between GLUT1 and DN, the above findings reinforce the need for further and more rigorous association studies.

Diabetic Nephropathies↗