PMID- 24594703
OWN - NLM
STAT- MEDLINE
DCOM- 20141104
LR  - 20221207
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 3
DP  - 2014
TI  - GRK5 intronic (CA)n polymorphisms associated with type 2 diabetes in Chinese 
      Hainan Island.
PG  - e90597
LID - 10.1371/journal.pone.0090597 [doi]
LID - e90597
AB  - A genome-wide association study had showed G-protein-coupled receptor kinase 5 
      (GRK5) rs10886471 was related to the risk of type 2 diabetes mellitus (T2DM) 
      through upregulated GRK5 mRNA expression. Rs10886471 is located in the intron 
      region of GRK5. However, the mechanism by which intronic SNP affects gene 
      expression remains unclear, whether the effect on gene expression depends on the 
      intronic short tandem repeat (STR) (CA)n splicing regulator or not. Here we 
      investigated the STR (CA)n polymorphism in rs10886471 and further discussed its 
      role in the T2DM risk of Chinese Hainan Island individuals. A total of 1164 
      subjects were recruited and classified into a normal fasting glucose (NFG) group, 
      an impaired fasting glucose (IFG) group, an impaired glucose tolerance (IGT) 
      group, and a T2DM group. STR (CA)n polymorphisms were detected through polymerase 
      chain reaction and sequencing. Five intronic (CA)n alleles, (CA)15 to (CA)19, 
      were identified in GRK5 rs10886471. Only the (CA)16 allele was significantly 
      associated with increased prediabetes and T2DM risk [odds ratio (OR)>1, P<0.05]. 
      Conversely, multiple alleles without any (CA)16 protected against prediabetes and 
      T2DM (0<OR<1, P<0.05). In summary, rs10886471 acts as both an SNP and an STR. The 
      rs10886471 intronic SNP causes GRK5 overexpression the subsequent risk of T2DM 
      may be due to the rs10886471 intronic STR (CA)n splicing enhancer. Further 
      studies should focus on verifying these finding using a large sample size and 
      analyzing the splicing mechanism of intronic (CA)n in rs10886471.
FAU - Xia, Zhenfang
AU  - Xia Z
AD  - Division of Health Statistics, School of Public Health, Central South University, 
      City of Changsha, Province Hunan, China.
FAU - Yang, Tubao
AU  - Yang T
AD  - Division of Health Statistics, School of Public Health, Central South University, 
      City of Changsha, Province Hunan, China.
FAU - Wang, Zhuansuo
AU  - Wang Z
AD  - Department of Endocrinology, the Affiliated Hospital of Hainan Medical College, 
      City of Haikou, Province Hainan, China.
FAU - Dong, Jianping
AU  - Dong J
AD  - Transgenic Laboratory, Hainan Medical College, City of Haikou, Province Hainan, 
      China.
FAU - Liang, Chunyan
AU  - Liang C
AD  - Outpatients Department, Community Health Service Center of Xiuying, City of 
      Haikou, Province Hainan, China.
LA  - eng
PT  - Journal Article
DEP - 20140303
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Blood Glucose)
RN  - EC 2.7.11.16 (G-Protein-Coupled Receptor Kinase 5)
RN  - EC 2.7.11.16 (GRK5 protein, human)
SB  - IM
MH  - Asian People/*genetics
MH  - Base Sequence
MH  - Blood Glucose/analysis
MH  - Diabetes Mellitus, Type 2/*genetics
MH  - G-Protein-Coupled Receptor Kinase 5/*genetics
MH  - Genetic Predisposition to Disease/*genetics
MH  - Genome-Wide Association Study
MH  - Humans
MH  - Introns/*genetics
MH  - Molecular Sequence Data
MH  - Odds Ratio
MH  - Polymerase Chain Reaction
MH  - Polymorphism, Genetic/*genetics
MH  - Sequence Analysis, DNA
PMC - PMC3940906
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2014/03/07 06:00
MHDA- 2014/11/05 06:00
PMCR- 2014/03/03
CRDT- 2014/03/06 06:00
PHST- 2013/10/27 00:00 [received]
PHST- 2014/02/01 00:00 [accepted]
PHST- 2014/03/06 06:00 [entrez]
PHST- 2014/03/07 06:00 [pubmed]
PHST- 2014/11/05 06:00 [medline]
PHST- 2014/03/03 00:00 [pmc-release]
AID - PONE-D-13-44878 [pii]
AID - 10.1371/journal.pone.0090597 [doi]
PST - epublish
SO  - PLoS One. 2014 Mar 3;9(3):e90597. doi: 10.1371/journal.pone.0090597. eCollection 
      2014.