Journal of the Neurological Sciences 344 (2014) 222

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Response to letter to the editor Responses to: Misconceptions surrounding the genetic susceptibility to ischemic stroke

Dear editor, We thank Dr. Sand PG for the comments on our paper titled: Three polymorphisms of ALOX5AP and risk of ischemic stroke in Chinese: Evidence from a meta-analysis [1]. For first question raised by Dr. Sand PG, we acknowledged that T carriers (AT+TT) of LOX5AP SG13S114A/T and A carries (AA+AT) overlapped, but we could confirm that A allele was associated with increased risk of ischemic stroke (IS), as combined odds ratio (OR) and 95% confidence interval (95% CI) for AA vs. TT was 1.47 (1.13–1.91), P = 0.005; and OR (95% CI) for A carries vs. TT for atherothrombotic-IS (AHS) was 1.17 (1.06–1.30), P = 0.002. For the second question, the method for selection of a scientific model remained uncertain for a meta-analysis regarding genetic polymorphism. Although a published paper has introduced an approach to select a reasonable comparison model [2], it was, however, not applicable. For the third question, we acknowledged that multiple-correction should be done for statistical test. Because four comparisons were done for each genetic polymorphism of LOX5AP, the P b 0.0125(0.05/4) should be used for statistical significance. After multiple adjustments for statistical test, A allele of LOX5AP SG13S114A/T was also suggested to be associated with increased risk of IS in Chinese, as P value for AA vs. TT for IS was 0.005 b 0.0125, and for A carries vs. TT for AHS was 0.002. For the fourth question, there was one study for LOX5AP SG13S114A/ T [3] and two studies for SG13S32A/C [4,5] that violated the HWE (Hardy–Weinberg equilibrium) in control group, as indicated in the paper (P b 0.05 indicated the violation of HWE). For LOX5AP SG13S114A/T, the study by Gao et al (2010) [3] violated the HWE in control group, and had highly discrepant allele frequencies. When the combined analysis was conducted by excluding this study, from supplementary Figure (A) in our paper (sensitivity analysis) [1], we could find that A allele was still associated with increased risk of IS in Chinese.

http://dx.doi.org/10.1016/j.jns.2014.06.010 0022-510X/© 2014 Elsevier B.V. All rights reserved.

Similarly, by excluding the two studies [4,5] violating the HWE in control groups, a combined analysis indicated that LOX5AP SG13S32A/C was also not associated with risk of IS. At last, detailed information for LOX5AP SG13S114A/T, SG13S89A/G and SG13S32A/C could be available on the NCBI database (http://www.ncbi.nlm.nih.gov/SNP). Formative names for LOX5AP SG13S114A/T, SG13S89A/G and SG13S32A/C were rs10507391, rs4769874 and rs9551963, respectively. Disclosure of interest All authors declaim no conflict of interest. References [1] Ye F, Liu NN, Zheng YQ, Zhang WJ, Wang CM, Xu Y, et al. Three polymorphisms of ALOX5AP and risk of ischemic stroke in Chinese: evidence from a meta-analysis. J Neurol Sci 2014;336:93–8. [2] Thakkinstian A, McElduff P, D'Este C, Duffy D, Attia J. A method for meta-analysis of molecular association studies. Stat Med 2005;24:1291–306. [3] Gao Z, Tan G-P. Relationship between ALOX5AP gene single nucleotide polymorphism and stroke of Han population in Shenyang City. J Apoplexy Nerv Dis 2010;27:1022–6. [4] Zhao J, Wang X, Xu J, Li N, Shang X, He Z, et al. Association of inflammatory response gene polymorphism with atherothrombotic stroke in Northern Han Chinese. Acta Biochim Biophys Sin (Shanghai) 2012;44:1023–30. [5] Xu J-L, He Z-Y, Li N, Deng S-M, Liu F, QIn X, et al. Association of polymorphisms of 5lipoxygenase activating protein and interleukin-1A genes with ischemic stroke. Zhonghua Shen Jing Ge Za Zhi 2009;42:803–7.

Fei Ye* Nan-Nuan Liu Yong-Qiang Zheng Wen-Jun Zhang Department of Neurology of Ren Min Hospital, Hubei University of Medicine, Hubei Province, PR China ⁎Corresponding author. E-mail address: [email protected] (F. Ye).

6 June 2014

Responses to: Misconceptions surrounding the genetic susceptibility to ischemic stroke.

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