Interaction between HLA-DRB1 gene polymorphism and environmental risk factors in the development of gestational diabetes mellitus

Abstract

Objective To explore the interactions between human leukocyte antigen ( HLA)-DRB1 gene polymorphism and environmental risk factors in gestational diabetes mellitus ( GDM ) pathogenesis.Methods Pregnant women who had prenatal cares in Obstetric Department , West China Second Hospital of Sichuan University were recruited from January 1st to December 31st in 2011.A prospective cohort study was conducted in the women who had a glucose challenge test ( GCT) or 75 g oral glucose tolerance test ( OGTT) during 24-28 gestational weeks.A total of 104 women diagnosed with GDM were randomly included in GDM group while another 103 normal women fell into the control group.The HLA-DRB1 polymorphism was detected by Polymerase Chain Reaction -Sequence Specific Primers ( PCR-SSP) method in both groups.The interactions between HLA-DRB1 polymorphism and environmental risk factors were analyzed based on the simple-case-study method.Results ( 1 ) There were 712 pregnant women with complete perinatal information during January 1st to December 31st, 2011, among whom 175 (24.6%) women were diagnosed with GDM.A logistic regression analysis showed that advanced maternal age (OR=1.081, 95%CI:1.027-1.138), imbalanced diet (OR=3.329, 95%CI:2.167 -5.116), high body mass index (BMI≥24.0 kg/m2) before pregnancy (OR=1.095, 95%CI:1.008 -1.190), HBsAg carrier status (OR=3.173, 95%CI:1.387-7.260) and family history of diabetes mellitus (DM) (OR=1.798, 95%CI:1.063 -3.041) were risk factors of GDM.(2) There were 49 HLA-DRB1 genotypes and 51 HLA-DRB1 genotypes in GDM group and the control group , respectively.We further compared the genotypes that occurred in over 3 cases in either group and found that HLA-DRB1*12,16 was only detected in 5 cases (5/103, 4.9%) in control group,and the difference was significant between the two groups (P=0.029).HLA-DRB1*11,16 and HLA-DRB1*09,09 were only detected in 4 cases (3.8%,4/104) and 5 cases (4.8%, 5/104) in GDM group respectively , but without significant differences between the two groups ( P >0.05 ).No significant difference was found in other genotype frequencies between the two groups ( P>0.05 ).( 3 ) Thirteen types of HLA-DRB1 allele were detected but no significant differences were observed in their frequencies between two groups ( P>0.05).(4) A positive interaction was detected between HLA-DRB1*07 polymorphism and advanced maternal ages (OR=5.952, 95%CI:1.314-26.970, P=0.022), while no interaction was found between HLA-DRB polymorphisms to other risk factors such as imbalanced diet , high body mass index ( BMI≥24.0 kg/m2 ) , HBsAg carrier status or DM family history.Conclusions Advanced maternal age, unbalanced diet, high body mass index (BMI≥24.0 kg/m2), HBsAg carrier status and DM family history are environmental risk factors of GDM in Chengdu.While HLA-DRB1*12,16 genotype may be a protective genotype for GDM.There is a positive interaction between HLA-DRB1*07 polymorphism and advanced maternal age which may play a critic role in GDM development. Key words: Diabetes,gestational ; HLA-DRB1 chains ; Polymorphism,genetic ; Risk factors ; Gene-environment interaction ;