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.
Chang
S-J
SJ
Department of Public Health, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. changsj@kmu.edu.tw
Tsai
M-H
MH
Ko
Y-C
YC
Tsai
P-C
PC
Chen
C-J
CJ
Lai
H-M
HM
D000328:Adult; D016022:Case-Control Studies; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics*; D062967:Cyclic GMP-Dependent Protein Kinase Type II; D017869:Cyclic GMP-Dependent Protein Kinases / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006073:Gout / Q000235:genetics*; D006801:Humans; D008126:Lod Score; D008297:Male; D010375:Pedigree; D011110:Polymorphism, Genetic
D062967:Cyclic GMP-Dependent Protein Kinase Type II; D017869:Cyclic GMP-Dependent Protein Kinases; C569729:PRKG2 protein, human