Korean Diabetes J.  2010 Dec;34(6):368-373. 10.4093/kdj.2010.34.6.368.

R1467H Variants of Rho Guanine Nucleotide Exchange Factor 11 (ARHGEF11) are Associated with Type 2 Diabetes Mellitus in Koreans

Affiliations
  • 1Diabetes Clinical Research Center, Inha University Hospital, Inha University College of Medicine, Incheon, Korea. namms@inha.ac.kr
  • 2Department of Internal Medicine, Inha University Hospital, Inha University College of Medicine, Incheon, Korea.
  • 3Department of Preventive and Social Medicine, Inha University College of Medicine, Incheon, Korea.

Abstract

BACKGROUND
The human Rho guanine nucleotide exchange factor 11 (ARHGEF11) functions as an activator of Rho GTPases and is thought to influence insulin signaling. The R1467H variant of ARHGEF11 has been reported to be associated with susceptibility to type 2 diabetes mellitus (T2DM) in Western populations.
METHODS
We investigated the effects of the R1467H variant on susceptibility to T2DM as well as related traits in a Korean population. We genotyped the R1467H (rs945508) of ARHGEF11 in 689 unrelated T2DM patients and 249 non-diabetic individuals and compared the clinical and biochemical characteristics according to different alleles.
RESULTS
The H allele was significantly more frequent in T2DM cases than in controls (P = 0.037, 17.1% and 13.1%; respectively). H homozygocity was associated with a higher risk of T2DM compared to those with R/R or R/H genotype (odds ratio, 5.24; 95% confidence interval, 1.06 to 25.83; P = 0.042). The fasting plasma glucose, HbA1c, fasting insulin, HOMA2-IR and HOMA2-%beta levels did not differ significantly between different genotypes.
CONCLUSION
Our study replicated associations of the ARHGEF11 polymorphism with increased risk of T2DM in a Korean population and thus supports previous data implicating a potential role of ARHGEF11 in the etiology of T2DM. Further studies revealing the underlying mechanism for this association are needed.

Keyword

Diabetes mellitus, type 2; Korean; Rho guanine nucleotide exchange factor 11; Single nucleotide polymorphism; Susceptibility gene

MeSH Terms

Alleles
Diabetes Mellitus, Type 2
Fasting
Genotype
Glucose
Guanine
Guanine Nucleotide Exchange Factors
Humans
Insulin
Plasma
Polymorphism, Single Nucleotide
rho GTP-Binding Proteins
Glucose
Guanine
Guanine Nucleotide Exchange Factors
Insulin
rho GTP-Binding Proteins

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