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Need for clarification of data in the meta-analysis about APOE gene polymorphism and primary open-angle glaucoma risk.

Posted by liaorongfeng001 on 09 Feb 2014 at 14:20 GMT

To the Editor:
Recently, we have read with interest in the study “Role of the APOE ε2/ε3/ε4 Polymorphism in the Development of Primary Open-Angle Glaucoma: Evidence from a Comprehensive Meta-Analysis” based on 9 case-control studies and published in the November 2013 issue of PLOS ONE.[1] Song et al. [1] conducted the meta-analysis to evaluate the association between the apolipoprotein E (APOE) gene ε2/ε3/ε4 polymorphism and the risk of primary open-angle glaucoma (POAG), and found no association between the APOE gene and the POAG risk.
However, some issues need to be addressed about this meta-analysis: (1) importantly, in the section of data extraction, the authors included two “eligible studies” which were published using the same case series obviously. The study with the smaller sample size should be excluded. [2-3] (2) It must be pointed that the eligible studies of the meta-analysis included a study evaluated the association between the APOE gene and the patients who with both POAG and Alzheimer's disease (AD). [4] However, APOE ε4 allele was regarded as a major risk for AD, the frequencies of APOE genotypes may be affected by AD in the patients who also with POAG. (3) Moreover, using the same search strategy as that of Song et al. [1], we found a study provided sufficient data about alleles (ε2, ε3, ε4) of APOE gene which could be regarded a useful data to evaluate the association between the alleles and POAG risk, although the study did not provide the distributions of genotypes (ε2/ε2, ε2/ε3, ε2/ε4, ε3/ε3, ε3/ε4, ε4/ε4) for the cases and controls. [5] (4) as the authors mentioned in the meta-analysis, there were several limitations affected the objective results. Some relevant published studies or unpublished studies were missed, which might generate publication bias.

References
1. Song Q, Chen P, Liu Q (2013) Role of the APOE ε2/ε3/ε4 polymorphism in the development of primary open-angle glaucoma: evidence from a comprehensive meta-analysis. PLoS One 27;8:e82347. doi: 10.1371/journal.pone.0082347.
2. Fan BJ, Wang DY, Fan DS, Tam PO, Lam DS, et al. (2005) SNPs and interaction analyses of myocilin, optineurin, and apolipoprotein E in primary open angle glaucoma patients. Mol Vis 29;11:625-631.
3. Lam CY, Fan BJ, Wang DY, Tam PO, Yung Tham CC, et al. (2006) Association of apolipoprotein E polymorphisms with normal tension glaucoma in a Chinese population. J Glaucoma15:218-222.
4. Tamura H, Kawakami H, Kanamoto T, Kato T, Yokoyama T, et al. (2006) High frequency of open-angle glaucoma in Japanese patients with Alzheimer's disease. J Neurol Sci246:79-83.
5. Ressiniotis T, Griffiths PG, Birch M, Keers S, Chinnery PF. (2004) The role of apolipoprotein E gene polymorphisms in primary open-angle glaucoma. Arch Ophthalmol122:258-261.

No competing interests declared.

RE: Need for clarification of data in the meta-analysis about APOE gene polymorphism and primary open-angle glaucoma risk.

songql replied to liaorongfeng001 on 25 Feb 2014 at 14:40 GMT

We are grateful to Dr Rongfeng Liao for his interest and thoughtful comments in reference to our article “Role of the APOE ε2/ε3/ε4 Polymorphism in the Development of Primary Open-Angle Glaucoma: Evidence from a Comprehensive Meta-Analysis” which was in the November 2013 issue of PLOS ONE. We appreciate the opportunity to respond to the letter.
In regards to the first comment, we appreciate the writers' thoroughness in checking our search for studies complying with our inclusion/exclusion criteria. However, just as we stated in the section of “Identification and eligibility of relevant studies”, the two studies you mentioned were conducted by different research group in spite of using the same case series, so at last we included them in our meta-analysis to ensure the accuracy of the results.
We agree that AD and glaucoma share some common features; the prevalence of POAG is greater in AD patients and an association between POAG and Alzheimer’s disease exists. However, due to the lack of POAG subtype information about AD background from the eligible studies, we did not performed the sub-group analyses about AD background in the POAG in our meta-analysis, and listed this limitation in the section of “Discussion”.
With regard to the process of identifying the relevant published articles, we developed the strict inclusion/exclusion criteria to secure the accuracy of results. So the study as you mentioned was excluded due to insufficient data. It is generally known that some excluded studies or unpublished studies might influence the results to some extent, however, some limitations were inevitable for a meta-analysis. Furthermore, we also listed the possible limitations in the section of “Discussion”. Certainly, further well-designed case-control studies with adequate numbers of cases are warranted to confirm our findings.
Thank you again for your constructive comments and reasonable questions concerning our article. The authors certify that there is no financial conflict of interest.

No competing interests declared.