Associations of polymorphisms in the candidate genes for Alzheimer's disease BIN1, CLU, CR1 and PICALM with gestational diabetes and impaired glucose tolerance.
Alzheimer's disease (AD) is the most common type of dementia, with a prevalence that is rising every year. AD is associated with type 2 diabetes mellitus (T2DM) and insulin resistance, and is therefore sometimes called "type 3 diabetes mellitus". The aim of this study was to examine whether the variants of some candidate genes involved in the development of AD, namely BIN1 (rs744373), CLU (rs11136000), CR1 (rs3818361), and PICALM (rs3851179), are related to several disorders of glucose metabolism-gestational diabetes (GDM), T2DM and impaired glucose tolerance (IGT). Our study included 550 women with former GDM and 717 control women, 392 patients with T2DM and 180 non-diabetic controls, and 117 patients with IGT and 630 controls with normal glucose tolerance. Genotyping analysis was performed using specially-designed TaqMan assays. No significant associations of the genetic variants rs744373 in BIN1, rs11136000 in CLU, or rs3818361 in CR1 were found with GDM, T2DM or IGT, but rs3851179 in PICALM was associated with an increased risk of GDM. The frequency of the AD risk-associated C allele was significantly higher in the GDM group compared to controls: OR 1.21; 95% CI (1.03-1.44). This finding was not apparent in T2DM and IGT; conversely, the C allele of the PICALM SNP was protective for IGT: OR 0.67; 95% CI (0.51-0.89). This study demonstrates an association between PICALM rs3851179 and GDM as well as IGT. However, elucidation of the possible role of this gene in the pathogenesis of GDM requires further independent studies.
Department of Molecular Endocrinology, Institute of Endocrinology, Národní 8, Prague, 116 94, Czech Republic. gvacinova@endo.cz.|Department of Anthropology and Human Genetics, Faculty of Science, Charles University in Prague, Prague, Czech Republic. gvacinova@endo.cz.
Gabriela
G
Vacínová
Department of Molecular Endocrinology, Institute of Endocrinology, Národní 8, Prague, 116 94, Czech Republic.
D
D
Vejražková
Department of Molecular Endocrinology, Institute of Endocrinology, Národní 8, Prague, 116 94, Czech Republic.
P
P
Lukášová
Department of Molecular Endocrinology, Institute of Endocrinology, Národní 8, Prague, 116 94, Czech Republic.
O
O
Lischková
Department of Molecular Endocrinology, Institute of Endocrinology, Národní 8, Prague, 116 94, Czech Republic.
K
K
Dvořáková
Thomayer Hospital, Prague, Czech Republic.|Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine and General University Hospital in Prague, Charles University in Prague, Prague, Czech Republic.
R
R
Rusina
Faculty of Humanities, Charles University in Prague, Prague, Czech Republic.
I
I
Holmerová
Faculty of Humanities, Charles University in Prague, Prague, Czech Republic.|Third Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
H
H
Vaňková
Department of Molecular Endocrinology, Institute of Endocrinology, Národní 8, Prague, 116 94, Czech Republic.
J
J
Včelák
Department of Molecular Endocrinology, Institute of Endocrinology, Národní 8, Prague, 116 94, Czech Republic.
B
B
Bendlová
Department of Molecular Endocrinology, Institute of Endocrinology, Národní 8, Prague, 116 94, Czech Republic.
M
M
Vaňková
D048868:Adaptor Proteins, Signal Transducing / Q000097:blood / Q000235:genetics; D000328:Adult; D000368:Aged; D000483:Alleles; D000544:Alzheimer Disease / Q000150:complications / Q000235:genetics*; D051152:Clusterin / Q000097:blood / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D016640:Diabetes, Gestational / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies / Q000379:methods; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D018149:Glucose Intolerance / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D034041:Monomeric Clathrin Assembly Proteins / Q000097:blood / Q000235:genetics*; D009687:Nuclear Proteins / Q000097:blood / Q000235:genetics; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011247:Pregnancy; D017463:Receptors, Complement 3b / Q000097:blood / Q000235:genetics; D012307:Risk Factors; D025521:Tumor Suppressor Proteins / Q000097:blood / Q000235:genetics; D044465:White People / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; C101410:BIN1 protein, human; C495242:CLU protein, human; C509991:CR1 protein, human; D051152:Clusterin; D034041:Monomeric Clathrin Assembly Proteins; D009687:Nuclear Proteins; C439003:PICALM protein, human; D017463:Receptors, Complement 3b; D025521:Tumor Suppressor Proteins
Alzheimer’s disease; Gestational diabetes mellitus; Glucose metabolism; Impaired glucose tolerance; Polymorphisms; Type 2 diabetes mellitus