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Chang, S.J. et al.

S.J. Chang, M.H. Tsai, Y.C. Ko, P.C. Tsai, C.J. Chen, H.M. Lai,

The cyclic GMP-dependent protein kinase II gene associates with gout disease: identified by genome-wide analysis and case-control study.

OBJECTIVE: To identify the position of a gout susceptibility gene. METHODS: A genome-wide scan was performed using 382 random polymorphic microsatellite markers spread across 22 autosomes in a Taiwanese family with gout to screen for the gout susceptibility genetic marker. Its association with gout by 33 single nucleotide polymorphisms (SNP) in 148 matched case-control subjects was confirmed. The family with gout comprised eight patients with gout and 10 gout-free subjects; case-control subjects were 74 male patients with gout and 74 healthy controls matched by age. RESULTS: Analysis of the genome-wide scan results by a non-parametric linkage method found that chromosome 4q21 contains a locus significantly linked with gout (D4S3243 at 81 289 553 bp; p = 0.004; LOD score = 5.13). In SNP genotyping analysis at the neighbourhood 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 hyperuricaemia (OR = 2.89, 95% CI 1.19 to 7.02 and OR = 2.72, 95% CI 1.13 to 6.54, respectively). CONCLUSIONS: This study suggests that the cGK II gene on chromosome 4q21 is most likely to harbour gout disease independently of hyperuricaemia and is inherited recessively.[1]

References

The cyclic GMP-dependent protein kinase II gene associates with gout disease: identified by genome-wide analysis and case-control study. Chang, S.J., Tsai, M.H., Ko, Y.C., Tsai, P.C., Chen, C.J., Lai, H.M. Ann. Rheum. Dis. (2009) [Pubmed]

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