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LETTER TO THE EDITOR
Year : 2012  |  Volume : 18  |  Issue : 2  |  Page : 270
 

Large scale meta-analysis of genetic studies in ischemic stroke: Five genes involving 152,297 individuals


1 Department of Neurology, All India Institute of Medical Sciences, New Delhi, India
2 Division of Paediatric Neurology, Department of Paediatrics, PGIMER, Chandigarh, India

Date of Web Publication8-Sep-2012

Correspondence Address:
Amit Kumar
Neuroscience Center, Department of Neurology, All India Institute of Medical Sciences
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0971-6866.100786

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How to cite this article:
Kumar A, Kumar P, Sahu JK. Large scale meta-analysis of genetic studies in ischemic stroke: Five genes involving 152,297 individuals. Indian J Hum Genet 2012;18:270

How to cite this URL:
Kumar A, Kumar P, Sahu JK. Large scale meta-analysis of genetic studies in ischemic stroke: Five genes involving 152,297 individuals. Indian J Hum Genet [serial online] 2012 [cited 2016 Jun 1];18:270. Available from: http://www.ijhg.com/text.asp?2012/18/2/270/100786


Sir,

The systematic review done by Hamzi et al. [1] on large scale meta-analysis of genetic studies in ischemic stroke suggested that there were significant association of five genes with ischemic stroke and it is necessary to compete with other genes. This systematic review requires re-evaluation as this study has important potential limitations.

First, the authors have analyzed five candidate gene variants namely Prothrombin, Factor V Leiden, Angiotensin Converting Enzyme (ACE), Methylene Tetra hydroxyfolate Reductase (MHFTR) and Apo-lipoprotein E (APOE) genes among 152,797 participants (45,433 cases and 107,364 controls). However, there is a major discrepancy in calculation of total number of participants as there is duplication of some data. For instance, (see page 214, [Table 4]) for MTHFR polymorphism, authors duplicated same reference Casas et al. [2] with different sample size (3,387 cases, 4,597 controls and 6,324 cases, 7,604 controls), which had increased the sample size and lead to misinterpretation of the results. Furthermore, authors have duplicated the studies [3],[4] in the [Table 4] , which were already included in Casas

et al. [2] meta-analysis, which resulted in wrong calculation of MTHFR gene sub-total Odds ratio .

Second concern is that the authors have followed the same criteria for selection of studies for other four genes polymorphisms (Prothrombin, Factor V Leiden, ACE and APOE gene meta-analysis which had also increased the total sample size and lead to faulty interpretation of the results. Even authors have not mentioned about heterogeneity of the study result, which is important to avoid bias due to variation in study outcomes between studies. So, readers should interpret this study with caution as there are important shortcomings in the study.

 
   References Top

1.Hamzi K, Tazzite A, Nadifi S. Large-scale meta-analysis of genetic studies in ischemic stroke: Five genes involving 152,797 individuals. Indian J Hum Genet 2011;17:212-7.  Back to cited text no. 1
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2.Casas JP, Hingorani AD, Bautista LE, Sharma P. Meta-analysis of genetic studies in ischemic stroke: Thirty-two genes involving approximately 18,000 cases and 58,000 controls. Arch Neurol 2004;61:1652-61.  Back to cited text no. 2
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3.Topiæ E, Simundiæ AM, Ttefanoviæ M, Demarin V, Vukoviæ V, Lovrenciæ-Huzjan A, et al . Polymorphism of apoprotein E (APOE), methylenetetrahydrofolate reductase (MTHFR) and paraoxonase (PON1) genes in patients with cerebrovascular disease. Clin Chem Lab Med 2001;39:346-50.  Back to cited text no. 3
    
4.Ariyaratnam R, Casas JP, Whittaker J, Smeeth L, Hingorani AD, Sharma P. Genetics of ischemic stroke among persons of non-European descent: A meta-analysis of eight genes involving approximately 32,500 individuals. PLoS Med 2007;4:e131.  Back to cited text no. 4
    




 

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