962049 letter2020

EJO0010.1177/1120672120962049European Journal of OphthalmologyUlhaq

EJO

Letter to the Editor

Comment on the assessment of “Association of interleukin-6 gene polymorphisms and glaucoma: systematic review and meta-analysis”

European Journal of Ophthalmology

European Journal of Ophthalmology 1­ © The Author(s) 2020 Article reuse guidelines: sagepub.com/journals-permissions https://doi.org/10.1177/1120672120962049 DOI: 10.1177/1120672120962049 journals.sagepub.com/home/ejo

Zulvikar Syambani Ulhaq Dear Editor, Wu et al.1 recently published an article on “the association of interleukin-6 gene polymorphisms and glaucoma: systematic review and meta-analysis.” Their study is one of the first works to analyze the relationship between IL-6 polymorphisms on the risk of glaucoma. However, the results and conclusion reported by the authors are inaccurate, which were driven by methodological errors. Here, I would like to discuss these issues. In the results section, the authors mention “subjects with the G allele presented an increased glaucoma risk (OR = 1.04, 95% CI = 0.80–1.36, p = 0.744) compared with individuals with the C allele” and “individuals carrying the G/G+G/C genotypes of the IL-6 rs1800795 polymorphism had a higher glaucoma risk (OR = 1.29, 95% CI = 0.76–2.19, p = 0.347) than did those who carried the C/C genotype,” these statements are not true, because p-values were more than 0.05. Additionally, these statements are contradicted with the other finding, such as “in the recessive model, no significant higher risk of glaucoma (OR = 0.97, 95% CI = 0.68–1.37, p = 0.850),” in which also having p-value more than 0.05. Thus, the results should be corrected as follows “no significant association between IL-6 rs1800795 with glaucoma in any models.” Because meta-analysis is the statistical combination of results from two or more separate studies,2-8 the findings and conclusion stating that “IL-6 rs1524107 (dominant (C/C+C/T vs T/T) and recessive (C/C vs C/T+T/T) models) are associated with glaucoma risk” are inaccurate, as these outcomes are driven by a single study. Moreover, a meta-analysis of the association between IL-6 rs1524107 and glaucoma should not be performed, rather than directly referring to a previously reported

study. Similarly, subgroup analyses such as “NTG” for glaucoma subtype and “European” for ethnicity group are also driven by a single study. In summary, a single study is not enough to conduct a meta-analysis. Declaration of conflicting interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iD Zulvikar Syambani Ulhaq -1940

https://orcid.org/0000-0002-2659

References 1. Wu C-L, Yang Y-T, Wang Y-H, et al. Association of interleukin-6 gene polymorphisms and glaucoma: systematic review and meta-analysis. Eur J Ophthalmol. Epub ahead of print 6 July 2020. DOI: 10.1177/1120672120940198. 2. Ahn E and Kang H. Introduction to systematic review and meta-analysis. Korean J Anesthesiol 2018; 71: 103–112. Department of Biochemistry, Faculty of Medicine and Health Sciences, Maulana Malik Ibrahim State Islamic University of Malang, Batu, East Java, Indonesia Corresponding author: Zulvikar Syambani Ulhaq, Department of Biochemistry, Faculty of Medicine and Health Sciences, Maulana Malik Ibrahim State Islamic University of Malang, Jalan Locari - Tlekung, Junrejo, Batu, East Java 65151, Indonesia. Email: [email protected]

2 3. Ulhaq ZS. Chemokine IL-8 level in aqueous humor of openangle glaucoma: a meta-analysis. Arch Soc Esp Oftalmol 2020; 95: 114–119. 4. Ulhaq ZS. Update on “Associations of estrogen receptor alpha gene polymorphisms with type 2 diabetes mellitus and metabolic syndrome: a systematic review and metaanalysis.” Horm Metab Res 2020; 52: 67–70. 5. Ulhaq ZS. The association between genetic polymorphisms in estrogen receptor genes and the risk of ocular disease: a meta-analysis. Turk J Ophthalmol 2020; 50: 216–220.

European Journal of Ophthalmology 00(0) 6. Ulhaq ZS and Soraya GV. Aqueous humor interleukin-6 levels in primary open-angle glaucoma (POAG): a systematic review and meta-analysis. Arch Soc Esp Oftalmol 2020; 95: 315–321. 7. Ulhaq ZS and Garcia CP. Inflammation-related gene polymorphisms associated with Parkinson’s disease: an updated meta-analysis. Egypt J Medical Hum Genet 2020; 21: 14. 8. Ulhaq ZS and Garcia CP. Estrogen receptor beta (ESR2) gene polymorphism and susceptibility to dementia. Acta Neurol Belg. Epub ahead of print 25 April 2020. DOI: 10.1007/s13760-020-01360-z.