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Variants of ALPK1 with ABCG2, SLC2A9, and SLC22A12 increased the positive predictive value for gout

Journal of Human Genetics volume 63, pages 63–70 (2018)Cite this article

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Abstract

We investigated the interactions of ALPK1 variants and the loci of ABCG2, SLC2A9, and SLC22A12 on gout risk. We conducted two case–control studies. Participants were recruited from hospitals (n = 410; 104 gout cases and 306 controls) and communities (n = 678; 373 gout cases and 305 controls) in Taiwan. The genotypes of ALPK1 (rs11726117 M861T, rs231247 R1084R, and rs231253 3′ UTR), ABCG2 (rs2231142 Q141K and rs2231137 V12M), SLC2A9 (rs3733591 R265H and rs1014290), and SLC22A12 (rs3825016 H86H, rs11231825 H142H, and rs475688) were genotyped. Under a recessive model, the joint effects of ALPK1 variants and the SNPs rs2231142 of ABCG2, rs1014290 of SLC2A9, or rs475688 and rs3825016 of SLC22A12 were associated with gout. The rs11726117 [CC] of ALPK1 and rs2231142 [TT] of ABCG2 with the sequential addition of the rs1014290 [AA] of SLC2A9 and rs3825016 [CC] of SLC22A12 were associated with gout risk (odds ratio (OR): 13.01, 15.11, and 55.00 and positive predictive value (PPV): 56%, 69%, and 99% in the Han group, respectively; OR: 3.76, 5.78, and 12.30 and PPV: 74%, 80%, and 81% in the aboriginal group, respectively). Combined exposure to the four high-risk genotypes of ALPK1 and the uric-acid-related loci of ABCG2, SLC2A9, and SLC22A12 was associated with an increased gout risk and a high PPV for gout.

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Acknowledgements

This study is supported by Ministry of Science and Technology (MOST 105-2632-B-039-001 and MOST 106-2314-B-037-034), China Medical University (CMU105-S-01, 03, 04, 06; DMR-106–115), and Kaohsiung Medical University Research Foundation (KMU-M106006).

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Affiliations

  1. Department of Public Health and Environmental Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Hung-Pin Tu

  2. Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

    Hung-Pin Tu

  3. Key Laboratory of Vertebrate Evolution and Human Origins of Chinese Academy of Sciences, IVPP, CAS, Beijing, 100044, China

    Albert Min-Shan Ko

  4. Division of Plastic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

    Su-Shin Lee

  5. Environment-Omics-Disease Research Center, China Medical University Hospital, China Medical University, Taichung, 40402, Taiwan

    Chi-Pin Lee, Tzer-Min Kuo & Ying-Chin Ko

  6. Division of Immunology and Rheumatology, Department of Internal Medicine, China Medical University Hospital, Taichung, 404, Taiwan

    Chung-Ming Huang

  7. Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan

    Chung-Ming Huang

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  1. Hung-Pin Tu
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Correspondence to Ying-Chin Ko.

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Tu, HP., Min-Shan Ko, A., Lee, SS. et al. Variants of ALPK1 with ABCG2, SLC2A9, and SLC22A12 increased the positive predictive value for gout. J Hum Genet 63, 63–70 (2018). https://doi.org/10.1038/s10038-017-0368-9

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