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Association Study of DKK2 Polymorphisms with Alcohol Dependence and Alcohol-Related Harm

Authors

  • Jason Yongha Kim,

    1. Department of Life Science, Sogang University, Seoul, Republic of Korea
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    • These authors have equal contributions to this study.
  • Joon Seol Bae,

    1. Department of Life Science, Sogang University, Seoul, Republic of Korea
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    • These authors have equal contributions to this study.
  • Byung Lae Park,

    1. Department of Genetic Epidemiology, SNP Genetics Inc., Seoul, Republic of Korea
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  • Jeong-Hyun Kim,

    1. Department of Life Science, Sogang University, Seoul, Republic of Korea
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  • Lyoung Hyo Kim,

    1. Department of Life Science, Sogang University, Seoul, Republic of Korea
    2. Department of Genetic Epidemiology, SNP Genetics Inc., Seoul, Republic of Korea
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  • Jee Wook Kim,

    1. Department of Neuropsychiatry, Hallym University Burn Institute, Seoul, Republic of Korea
    2. Department of Neuropsychiatry, Hallym University Dongtan Sacred Heart Hospital, Hwaseong, Gyeonggi Province, Republic of Korea
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  • Boung Chul Lee,

    1. Department of Neuropsychiatry, Hallym University Burn Institute, Seoul, Republic of Korea
    2. Department of Neuropsychiatry, Hangang Sacred Heart Hospital, Hallym University, Seoul, Republic of Korea
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  • Tae-Cheon Kang,

    1. Department of Anatomy and Neurobiology, College of Medicine, Hallym University, Chuncheon, Republic of Korea
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  • Ihn-Geun Choi,

    Corresponding author
    1. Department of Neuropsychiatry, Hallym University Burn Institute, Seoul, Republic of Korea
    2. Department of Neuropsychiatry, Hallym University Kangnam Sacred Heart Hospital, Seoul, Republic of Korea
    • Reprint requests: Ihn-Geun Choi, MD, PhD, Department of Neuropsychiatry, Hallym University Kangnam Sacred Heart Hospital, 948-1 Daerim 1-Dong, Yeongdeungpo-Gu, Seoul, 150-950, Republic of Korea. Tel.: +82 2 845 5194; Fax: +82 2 849 4469; E-mail: ihngeun@naver.com; Hyoung Doo Shin, PhD, Department of Life Science, Sogang University, 1 Shinsu-dong, Mapo-gu, Seoul, 121-742, Republic of Korea. Tel.: +82 2 705 8615; Fax: +82 2 3723 1680; E-mail: hdshin@sogang.ac.kr

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  • Hyoung Doo Shin

    1. Department of Life Science, Sogang University, Seoul, Republic of Korea
    2. Department of Genetic Epidemiology, SNP Genetics Inc., Seoul, Republic of Korea
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Abstract

Background

Alcohol dependence (AD) is a common disorder with both environmental and genetic factors. Previous studies have shown that the genomic region from chromosome 4q22-q32 is closely associated with AD. Furthermore, a study with Irish subjects revealed that the polymorphisms of Dickkopf WNT signaling pathway inhibitor (DKK2), located at 4q25, showed a significant association with AD.

Methods

We conducted a replication study of the association between DKK2 polymorphisms and AD with 459 alcoholics and 444 normal controls, all of Korean descendent. To rank the AD of the subjects, Alcohol Use Disorders Identification Test (AUDIT) was utilized. Using the TaqMan assay, 21 single-nucleotide polymorphisms (SNPs) of DKK2 were genotyped.

Results

Our analysis showed that rs17037102 (Q146R) was significantly associated with overall AUDIT score (= 0.003, pcorr = 0.05 in dominant model). Further analysis showed that the SNP was significantly associated with alcohol-related harm (= 0.001, pcorr = 0.02 in co-dominant model). Several other SNPs, including the 3 SNPs which were associated with AD in European population, showed marginal associations that were erased when corrections for multiple testing was applied. Furthermore, rs17037102 was in linkage disequilibrium with the nonexonic DKK2 SNPs which showed associations with AD in the previous study with Irish population, which suggests that rs17037102 may be the causal SNP.

Conclusions

We found 1 DKK2 SNP to be significantly associated with alcohol-related harm in alcoholic subjects. The SNP might be the causal SNP which led its linked SNPs to show associations in previous studies.

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