Influence of age on the association of GIRK4 with metabolic syndrome.
BACKGROUND
G protein-coupled inward rectifier K+ channel 4 (GIRK4) gene expressions have been implicated in the development of obesity, a key feature of metabolic syndrome (MetS). We investigated whether sequence variants of GIRK4 may represent metabolic risk factors for the Uygur Chinese population.


METHODS
The entire GIRK4 gene, including all exons, the promoter and untranslated regions from 48 MetS individuals, was studied in order to identify genetic variations associated with the disorder. Targeted genotyping of four common single nucleotide polymorphisms (SNPs: rs11221497, rs6590357, rs4937391 and rs2604204) and one novel missense mutation (M210I) was performed using the TaqMan polymerase chain reaction method for 443 MetS and 786 non-MetS subjects.


RESULTS
When all MetS cases were compared against all non-MetS controls, no significant association was found between the three SNPs (rs2604204, rs4937391 and rs6590357) and MetS status or metabolic traits. After adjustment, rs11221497 was associated with MetS (odds ratio (OR) [95% CI]=0.731 [0.551-0.968], P=0.029). Interestingly, when the MetS group was stratified into subclasses by age, an association was found for the three SNPs (rs2604204, rs4937391 and rs6590357) having estimated false discovery rates<0.001 and age of <50 y. After adjustment, the SNPs rs2604204, rs4937391 and rs6590357 were also associated with MetS in younger subjects: ORs [95% CI]: 1.678 [1.149-2.450], 1.839 [1.204-2.809] and 0.602 [0.379-0.958], respectively. All of the four SNPs showed a trend towards lower or higher metabolic traits (P<0.05) in younger subjects. In addition, a newly identified missense mutation (M210I) was not specifically related with MetS.


CONCLUSIONS
GIRK4 sequence variants appear to associate with MetS in the Uygurian population, and this association may be influenced by age.
The Center of Hypertension of the People's Hospital of Xinjiang Uygur Autonomous Region, Xinjiang 830001, China. lnanfang@yahoo.com.cn
Nanfang
N
Li
Delian
D
Zhang
Juhong
J
Zhang
Yanying
Y
Guo
Zhitao
Z
Yan
Hongmei
H
Wang
Ling
L
Zhou
Jing
J
Hong
Xinling
X
Wang
Zufeiya
Z
A
D000328:Adult; D000367:Age Factors; D016022:Case-Control Studies; D002681:China; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000235:genetics*; D006801:Humans; D024821:Metabolic Syndrome / Q000235:genetics*; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020506:Untranslated Regions
D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; C484274:KCNJ5 protein, human; D020506:Untranslated Regions