Is rs34861192 or rs1862513 a more promising varian

Authors: H Osawa Y Tabara J Ohashi R Kawamura H Onuma H Makino

Publish Date: 2010/02/04

Volume: 53, Issue: 4, Pages: 795-797

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Abstract

To the Editor In a recent paper Asano et al reported on an analysis of single nucleotide polymorphisms SNP of the human resistin gene RETN in an aged Japanese population and suggested that rs34861192 SNP638GA and rs3745368 3′ UTR are significant determinants of plasma resistin 1 We wish to report that this statement may cause readers to conclude erroneously that rs34861192 but not rs1862513 SNP420CG is a causal variant determining circulating resistin If the functional data were to be taken into account the interpretation of the genetic data would be differentIt appears to us that rs1862513 can still be considered to be a promising candidate for a causal variant as evidenced from findings available to date including their reported results 1 2 3 4 5 First it should be noted that their conclusion was drawn entirely from statistical analyses of genetic data These data should be interpreted with caution since it is not possible to assess the effect of A of rs34861192 independent of G of rs1862513 due to the absence of individuals having both the A/A genotype of rs34861192 and the C/C genotype of rs1862513 Second their conclusion was not verified by functional analyses Of rs34861192 rs1862513 and rs3219175 SNP358GA which is in complete linkage disequilibrium LD with rs34861192 functional roles have been proven only for rs1862513 in vitro 2 3 4 5Most crucially when the data in Fig 3 of Asano et al 1 are inspected carefully all individuals with the A/A genotype of rs34861192 also had the G/G genotype of rs1862513 There were no individuals with both the A/A genotype of rs34861192 and the C/C genotype of rs1862513 Therefore it is not possible to assess the effect of A of rs34861192 independent of G of rs1862513 Individuals with the A/A genotype of rs34861192 and the C/C genotype of rs1862513 should have been included in the analysis in order to determine which SNP is more critical for determining circulating resistin levels This does not appear to be feasible due to the very low frequency of individuals with the combination of these two genotypes which may be due to limitations in genetic epidemiology because of the available sample size In addition rs34861192 rs1862513 and rs3219175 are all located in the same LD block and all of these three SNPs are strongly associated with circulating resistin levels Based on their data rs34861192 and rs1862513 are in moderate LD r 2 = 047 When calculated from our previous data in 200 type 2 diabetic cases and in 200 controls 2 r 2 was similar to that of Asano et al r 2 = 051 and 057 respectively whereas D′ was 1 in both groups It should be pointed out that it is difficult to identify a causal variant from highly correlated SNPs by the exclusive use of statistical analyses of genetic data in the absence of other information 6

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