Screening for MODY mutations, GAD antibodies, and type 1 diabetes--associated HLA genotypes in women with gestational diabetes mellitus.
OBJECTIVE
To investigate whether genetic susceptibility to type 1 diabetes or maturity-onset diabetes of the young (MODY) increases susceptibility to gestational diabetes mellitus (GDM).


METHODS
We studied mutations in MODY1-4 genes, the presence of GAD antibodies, and HLA DQB1 risk genotypes in 66 Swedish women with GDM and a family history of diabetes. An oral glucose tolerance test was repeated in 46 women at 1 year postpartum.


RESULTS
There was no increase in type 1 diabetes-associated HLA-DQB1 alleles or GAD antibodies when compared with a group of type 2 diabetic patients (n = 82) or healthy control subjects (n = 86). Mutations in known MODY genes were identified in 3 of the 66 subjects (1 MODY2, 1 MODY3, and 1 MODY4). Of the 46 GDM subjects, 2 had diabetes (4%) and 17 had impaired glucose tolerance (IGT) (37%) at 1 year postpartum. Of the two subjects who developed manifest diabetes, one carried a MODY3 mutation (A203H in the hepatocyte nuclear factor-1alpha gene). There was no increase in high-risk HLA alleles or GAD antibodies in the women who had manifest diabetes or IGT at 1 year postpartum.


CONCLUSIONS
MODY mutations but not autoimmunity contribute to GDM in Swedish women with a family history of diabetes and increase the risk of subsequent diabetes.
Weng
Jianping
J
Department of Endocrinology, Malmö University Hospital, Lund University, Malmö, Sweden.
Ekelund
Magnus
M
Lehto
Markku
M
Li
Haiyan
H
Ekberg
Göran
G
Frid
Anders
A
Aberg
Anders
A
Groop
Leif C
LC
Berntorp
Kerstin
K
D000328:Adult; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D016640:Diabetes, Gestational / Q000235:genetics* / Q000276:immunology; D005260:Female; D005838:Genotype; D018149:Glucose Intolerance / Q000235:genetics / Q000276:immunology; D006680:HLA Antigens / Q000235:genetics*; D006683:HLA-DQ Antigens / Q000235:genetics*; D059866:HLA-DQ beta-Chains; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D018579:Patient Selection; D011247:Pregnancy; D018570:Risk Assessment; D013548:Sweden
D006680:HLA Antigens; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen