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The cyclic GMP-dependent protein kinase II gene associates with gout disease identified by genome-wide analysis and case-control study
  1. Shun-Jen Chang (changsj{at}kmu.edu.tw)
  1. Kaohsiung Medical University, Taiwan
    1. Ming-Hsien Tsai (u9351020{at}abo.kmu.edu.tw)
    1. Kaohsiung Medical University, Taiwan
      1. Ying-Chin Ko (ycko{at}kmu.edu.tw)
      1. Kaohsiung Medical University, Taiwan
        1. Pei-Chien Tsai (ambertpc{at}mail2000.com.tw)
        1. Kaohsiung Medical University, Taiwan
          1. Chung-Jen Chen (chungjen{at}adm.cgmh.org.tw)
          1. Chang Gung Memori Hospital- Kaohsiung Medical Center, Chang Gung University College of Medicine, Taiwan
            1. Han-Ming Lai (laihn{at}ms31.hinet.net)
            1. Chang Gung Memori Hospital- Kaohsiung Medical Center, Chang Gung University College of Medicine, Taiwan

              Abstract

              Objectives: To identify the position of a gout susceptibility gene.

              Methods: We performed a genome-wide scan method using 382 random polymorphic microsatellite markers spread across 22 autosomes in a Taiwanese gout family to screen the gout susceptibility genetic marker. We confirmed its association with gout disease by 33 single nucleotide polymorphisms (SNP) in 148 matched case-control subjects. The gout family was composed of eight gouty patients and ten gout-free subjects and the case-control subjects were 74 male gout patients and 74 healthy controls matched by age.

              Results: Analysis of the genome-wide scan result by a non- parametric linkage method found that chromosome 4q21 contains a locus significantly linked with gout disease (D4S3243 at 81,289,553 bp; p = 0.004; LOD score = 5.13). In SNP genotyping analysis at the neighborhood regions of marker D4S3243 for the case-control subjects, the polymorphisms rs7688672 and rs6837293, located on the cGMP-dependent protein kinase II (cGK II) gene, were found to relate significantly to gout disease in a recessive model after adjustment of hyperuricemia (OR=2.89, 95% CI=1.19-7.02 and OR=2.72, 95% CI=1.13-6.54 respectively).

              Conclusions: This study suggests the cGK II gene on chromosome 4q21 was most likely to harbor gout disease independent of hyperuricemia and inherited recessively.

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