Association of the E23K polymorphism in the KCNJ11 gene with gestational diabetes mellitus.
OBJECTIVE
Gestational diabetes mellitus (GDM) and type 2 diabetes share a common pathophysiological background, including beta cell dysfunction and insulin resistance. In addition, women with GDM are at increased risk of developing type 2 diabetes later in life. Our aim was to investigate whether, like type 2 diabetes, GDM has a genetic predisposition by studying five common polymorphisms in four candidate genes that have previously been associated with type 2 diabetes.


METHODS
We studied 1,777 unrelated Scandinavian women (588 with GDM and 1,189 pregnant non-diabetic controls) for polymorphisms in the genes encoding potassium inwardly rectifying channel subfamily J, member 11 (KCNJ11 E23K), insulin receptor substrate 1 (IRS1 G972R), uncoupling protein 2 (UCP2 -866G-->A) and calpain 10 (CAPN10 SNP43 and SNP44).


RESULTS
The EE, EK and KK genotype frequencies of the KCNJ11 E23K polymorphism differed significantly between GDM and control women (31.5, 52.7 and 15.8% vs 37.3, 48.8 and 13.9%, respectively; p=0.050). In addition, the frequency of the K allele was increased in women with GDM (odds ratio [OR]=1.17, 95% CI 1.02-1.35; p=0.027), and this effect was greater under a dominant model (KK/EK vs EE) (OR=1.3, 95% CI 1.05-1.60; p=0.016). Analysis of the IRS1 G972R polymorphism showed that RR homozygosity was found exclusively in women with GDM (91.0, 8.3 and 0.7% vs 90.7, 9.3 and 0.0% for GG, GR and RR genotypes, respectively; p=0.014). The genotype and allele frequencies of the other polymorphisms studied were not statistically different between the GDM and control women.


CONCLUSIONS
The E23K polymorphism of KCNJ11 seems to predispose to GDM in Scandinavian women.
Shaat
N
N
Department of Clinical Sciences/Diabetes and Endocrinology, Malmö University Hospital, Lund University, Malmö, Sweden. nael.shaat@med.lu.se
Ekelund
M
M
Lernmark
A
A
Ivarsson
S
S
Almgren
P
P
Berntorp
K
K
Groop
L
L
D000328:Adult; D000483:Alleles; D002154:Calpain / Q000235:genetics; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D016640:Diabetes, Gestational / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D055504:Insulin Receptor Substrate Proteins; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology; D050417:Insulin-Secreting Cells / Q000502:physiology; D007473:Ion Channels; D026901:Membrane Transport Proteins / Q000235:genetics; D024101:Mitochondrial Proteins / Q000235:genetics; D016017:Odds Ratio; D010750:Phosphoproteins / Q000235:genetics; D011110:Polymorphism, Genetic; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics* / Q000502:physiology; D011247:Pregnancy; D012306:Risk; D013548:Sweden / Q000453:epidemiology; D000071246:Uncoupling Protein 2; D000099161:Kcnj11 Channel
D002154:Calpain; D055504:Insulin Receptor Substrate Proteins; D007473:Ion Channels; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D010750:Phosphoproteins; D024661:Potassium Channels, Inwardly Rectifying; D000071246:Uncoupling Protein 2; D000099161:Kcnj11 Channel; C526292:IRS1 protein, human; C000604389:UCP2 protein, human; C415197:calpain 10