Homocysteine, B Vitamins, Methylenetetrahydrofolate Reductase Gene, and Risk of Primary Open-Angle Glaucoma

Xu, Fan; Zhao, Xin; Zeng, Siming; Li, Li; Zhong, Haibin; Li, Min

doi:10.1016/j.ophtha.2012.06.025

Cited by 29 publications

(23 citation statements)

References 35 publications

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“…On the other hand, several other studies suggested that MTHFR C677T polymorphism itself is not a major risk factor [10, 27] as these studies could not find any significant association with susceptibility risk of POAG in Japanese [28], Austrian [16], Swedish [18], Pakistani [6], Iranian [29], Mexican [30] and Greek populations [13]. …”

Section: Discussionmentioning

confidence: 99%

Association of the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism with primary glaucoma in Saudi population

et al. 2016

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BackgroundMethylenetetrahydrofolate reductase (MTHFR), a critical enzyme in folate metabolism is involved in DNA synthesis, DNA repair and DNA methylation. The functional polymorphism of MTHFR gene, C677T has been shown to impact various diseases and implicated as a risk factor for the development of various neurodegenerative disorders including glaucoma.MethodsWe investigated MTHFR C677T genotypes and alleles frequencies in primary glaucoma [primary open angle glaucoma (POAG) and primary angle closure glaucoma (PACG)] patients and matched healthy controls in a case-control study. Two hundred ten primary glaucoma cases were studied for MTHFR C677T polymorphism and compared with 280 controls taken from the healthy population, employing the polymerase chain reaction-restriction fragment length polymorphism technique (PCR-RFLP). The MTHFR gene was amplified using specific primers. The PCR products (294 bp) was subsequently digested with HinfI (New England Biolabs) at 37 °C for 12 h, separated by electrophoresis on 2 % agarose gels, and visualized with ethidium bromide staining. The restriction digestion yielded 168 and 126 bp fragments for TT, 294, 168 and 126 bp fragments for CT and undigested PCR product 294 bp indicating CC genotype.ResultsWe found the frequency of the genotypes and alleles of MTHFR C677T differ significantly between cases and controls. The frequencies of allele T and genotype CT were significantly higher while the frequencies of allele C and genotype CC were lower in primary glaucoma patients as compared to controls (p <0.05). Upon stratification of our results into POAG and PACG, significantly higher frequencies of allele T (19.44 %) and genotype CT (38.89 %) were found in POAG patients compared to controls (12.5 % and 25 % respectively). The frequencies of alleles and genotypes were almost similar in PACG and controls (p = 0.8).ConclusionThis study indicates that the allele T and genotype CT of MTHFR C677T polymorphism are significantly associated with POAG while allele C and CC genotype may be protective for it. We conclude that the MTHFR C677T polymorphism increases the risk for POAG development in Saudi population and can be a genetic marker however, further studies are needed with multiple-ethnic populations affected with POAG to strengthen these findings.

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Section: Discussionmentioning

confidence: 99%

Association of the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism with primary glaucoma in Saudi population

et al. 2016

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“…Increased serum and tear homocysteine levels were found to be present in patients with POAG 17,18. Elevated plasma homocysteine levels have also been found in patients with PXFG,19,20 and these findings were recently confirmed by two published meta-analyses 21,22. The genetic component of circulating homocysteine involves single nucleotide polymorphisms on five genes, ie, methylenetetrahydrofolate reductase ( MTHFR ), methionine synthase, methionine synthase reductase, methylenetetrahydrofolate dehydrogenase ( MTHFD1 ), and cystathionine β-synthase, encoding enzymes within the pathway of homocysteine metabolism on chromosomes 1, 5, 14, and 21.…”

Section: Introductionmentioning

confidence: 60%

Plasma homocysteine and genetic variants of homocysteine metabolism enzymes in patients from central Greece with primary open-angle glaucoma and pseudoexfoliation glaucoma

Zacharaki¹,

Hadjigeorgiou²,

Κολιάκος³

et al. 2014

OPTH

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BackgroundThe purpose of this study was to investigate plasma homocysteine levels and polymorphisms in genes encoding enzymes in the metabolic pathway of homocysteine in association with primary open-angle glaucoma (POAG) and pseudoexfoliation glaucoma (PXFG).MethodsA total of 156 glaucoma patients (76 with POAG and 80 with PXFG) and 135 controls matched for age and sex were enrolled in this study. Plasma homocysteine levels were measured using a commercially available enzyme-linked immunosorbent assay kit. DNA was extracted from peripheral blood leukocytes and real-time polymerase chain reaction was performed for genotyping of the samples. Patients were genotyped using predesigned TaqMan® single nucleotide polymorphism genotyping assays for two exon variations (rs1801131, rs1801133) in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene and one intron variation (rs8006686) in the methylenetetrahydrofolate dehydrogenase (MTHFD1) gene.ResultsHomocysteine levels were slightly higher in the patient group (POAG and PXFG) compared with controls, but the difference did not reach statistical significance. The minor alleles of the MTHFR single nucleotide polymorphisms showed a protective effect for POAG and showed an increased risk for PXFG, but none of these associations reached statistical significance (P>0.05). The minor allele of MTHFD1 rs8006686 showed a trend for increased risk of both POAG and PXFG (P>0.05). No statistically significant interaction was seen between the genetic variants and homocysteine levels (P>0.05).ConclusionOur results show that neither the examined single nucleotide polymorphisms from genes involved in the pathway of homocysteine metabolism nor the measured homocysteine levels were associated with POAG or PXFG in our study cohort.

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“…However, four studies did not find an association between MTHFR C677T polymorphism and POAG risk in Iranian, Mexican, Indian and Greek populations [25,[27][28][29]. In 2012, Xu et al have conducted the first meta-analysis including ten studies with 1,406 cases and 1,216 controls on MTHFR C677T polymorphism [38]. They found no impact of MTHFR C677T polymorphism on POAG susceptibility in the pooled analysis.…”

Section: Discussionmentioning

confidence: 99%

Association of MTHFR C677T and A1298C Polymorphisms with Glaucoma Risk: a Systematic Review Meta-Analysis based 42 Case-Control Studies

Gohari

Mirjalili

Akbarian-Bafghi

et al. 2019

rjo

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Aim: Several epidemiological studies have been performed to explore the association of MTHFR polymorphisms with glaucoma risk. However, the results were inconsistent or even inconclusive. Hence, we performed a meta-analysis to evaluate the association of MTHFR C677T and A1298C polymorphisms with glaucoma risk. Methods: A comprehensive literature search on PubMed, Google Scholar, EMBASE, and CNKI databases was performed to find all eligible studies up to January 30, 2019. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of such association. Results: A total of 42 case-control studies including 33 studies for MTHFR C677T and nine studies for A1298C polymorphism were selected. Pooled results showed that there was no significant association between the MTHFR C677T polymorphism and glaucoma risk. Similarly, no associations were found in subgroup analysis based on ethnicity and glaucoma type. However, there was a significant association between the A1298C polymorphism and the increased risk of glaucoma under heterozygote model (OR=0.765, 95% CI=0.626-0.935, P=0.009). Moreover, the significant association between MTHFR A1298C polymorphism and glaucoma were found by ethnicity and primary open angle glaucoma (POAG). Conclusions: The present meta-analysis revealed that MTHFR A1298C polymorphism is significantly associated with the increased risk of glaucoma, but not MTHFR C677T polymorphism.

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Homocysteine, B Vitamins, Methylenetetrahydrofolate Reductase Gene, and Risk of Primary Open-Angle Glaucoma

Cited by 29 publications

References 35 publications

Association of the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism with primary glaucoma in Saudi population

Association of the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism with primary glaucoma in Saudi population

Plasma homocysteine and genetic variants of homocysteine metabolism enzymes in patients from central Greece with primary open-angle glaucoma and pseudoexfoliation glaucoma

Association of MTHFR C677T and A1298C Polymorphisms with Glaucoma Risk: a Systematic Review Meta-Analysis based 42 Case-Control Studies

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