Mannose-Binding Lectin Gene Polymorphisms Are Associated with Gestational Diabetes Mellitus

Abstract

Insulin resistance is a feature of gestational diabetes mellitus (GDM). Inverse correlations between indexes of insulin sensitivity and serum markers of inflammation have been observed and, particularly, TNF-alpha has been shown to be associated with the appearance of insulin resistance in pregnancy. Mannose-binding lectin (MBL) is a protein member of the collectin family. Its deficiency is genetically determined and predisposes to recurrent infections and chronic inflammatory diseases. To test the hypothesis that a genetic predisposition to a proinflammatory state could favor the appearance of GDM during pregnancy, we studied R52C and G54D polymorphisms of MBL2 gene and plasma MBL levels from 105 consecutive GDM women and 173 healthy pregnant women. An association was found between G54D and GDM [odds ratio, 2.03 (1.18-3.49); P < 0.01], and this association remained significant when the presence of both mutated alleles was considered [odds ratio, 1.76 (1.04-2.96); P < 0.05] but not for the R52C. GDM patients who carried the G54D mutation required insulin therapy more frequently (56.4 vs. 30.4%, chi(2) =5.83; P = 0.027) and had heavier infants (3326.4 +/- 546.9 vs. 3087.5 +/- 395.5 g; P < 0.05) than GDM women homozygous for the wild-type allele. An inverse correlation in GDM patients between neonatal weight and plasma MBL levels (r = -0.320; P = 0.002) was found, remaining significant after adjustment for confounding variables. In conclusion, pregnant women bearing the G54D MBL allele have a greater risk for developing GDM and having heavier infants.

Protection from inflammatory disease in insulin resistance: the role of mannan-binding lectin

“…We have recently reported that pregnant women bearing MBL2 gene mutations had a greater risk of developing gestational diabetes and having heavier infants [15]. On the other hand, a high MBL level was also associated with a greatly decreased risk of myocardial infarction in diabetic or hypercholesterolaemic individuals in a recent report [16].…”

Transcriptome Analysis of K-877 (a Novel Selective PPARα Modulator (SPPARMα))-Regulated Genes in Primary Human Hepatocytes and the Mouse Liver

“…These include mannose-binding lectin 2 (MBL2) 49,50) and glutamyl aminopeptidase ENPEP 51,52) . MBL is an important protein of the humoral innate immune system, and it has been reported that the serum MBL concentrations are decreased in obese subjects, accompanied by an increase in inflammatory markers 49) .…”

“…MBL is an important protein of the humoral innate immune system, and it has been reported that the serum MBL concentrations are decreased in obese subjects, accompanied by an increase in inflammatory markers 49) . In addition, G54D MBL2 gene polymorphisms confer an increased risk for developing gestational diabetes mellitus 50) . ENPEP is an enzyme that facilitates the conversion of angiotensin , the main effector protein of the renin-angiotensin-aldosterone system, to angiotensin 51) .…”

Association of the E23K polymorphism in the KCNJ11 gene with gestational diabetes mellitus

“…Genetic predisposition to GDM has been reported for variations in the insulin receptor (INSR), insulin-like growth factor 2 (IGF2), β 3 -adrenergic receptor (ADRB3), sulphonylurea receptor 1 (ABCC8), CAPN10 and mannose-binding lectin (MBL2) genes [23][24][25][26][27], whereas no associations were found for the PPARG Pro12Ala polymorphism or insulin gene variable number of tandem repeats (INS VNTR) [28]. Also, an association with the ADRB3 W64R variant could not be replicated in subsequent studies [29,30].…”