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Title of Journal: Hum Genet

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Abbravation: Human Genetics

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Springer-Verlag

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ISSN

1432-1203

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Association tests of interleukin6 Emphasis Type

Authors: Peng Xiao PengYuan Liu Yan Lu YanFang Guo DongHai Xiong LiHua Li Robert R Recker HongWen Deng
Publish Date: 2005/05/20
Volume: 117, Issue: 4, Pages: 340-348
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Abstract

Interleukin 6 IL6 and tumor necrosis factor TNF are important cytokines for bone turnover In this study a promoter C174G singlenucleotide polymorphism SNP within the IL6 gene affecting the transcription rate of IL6 and an exon 6 T676G SNP of the TNF receptor 2 TNFR2 gene causing an M196R aminoacid change were examined for their relationship with bone mineral density BMD Four hundred and five multioffspring Caucasian families including 389 male children and 744 female children were used One thousand resamplings were conducted and in each data set one child was randomly chosen from each family For each data set oneway analysis of variance ANOVA test was independently implemented using age age2 sex height and weight as covariates There were 523 288 204 and 369 significant results out of 1000replicate resamplings of the data of the IL6 SNP P005 for onethird middistal ultradistal radius BMD and the first principal component PC1 extracted from the three radial BMDs respectively which means that the confidences for associations of the C174G SNP in the IL6 gene with onethird middistal ultradistal radius totally called distal forearm BMDs and PC1 were 523 288 204 and 369 respectively For this SNP with BMD at other skeletal sites and the TNFR2 T676G SNP with BMD at any site significant results were far less than 200 times out of 1000 resampling replicates The exceedingly consistent permutation results further improved the confidence of the associations It may imply that the IL6 C174G SNP is associated with distal forearm BMD but there is no evidence that the TNFR2 T676G SNP is related with BMD in US Caucasians This is the first attempt to conduct association test utilizing a resampling approach Our results may be more informative than other association analyses that were only based on one sampling result The results also suggest that different samplings could produce significantly diverse results even for the same population and the results from one sampling are unlikely to be conclusive Our results have significant implications for association studies and interpretation of nonreproducible association findingsThe study was partially supported by grants from Health Future Foundation National Institute of Health K01 AR0217001 R01 GM6040201A1 R01 AR05049601A1 the State of Nebraska LB595 and LB692 and US Department of Energy DEFG0300ER63000/A00 This study was also benefited from the 211 State Key Research Fund to Xi’an Jiaotong University grants from CNSF and Huo Ying Dong Education Fund of HongKong

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