摘要
目的：探讨人类白细胞抗原（ HLA）-DRB1基因多态性与妊娠期糖尿病（ GDM）危险因素间的交互作用在GDM发病中的作用。方法选择2011年1月1日-12月31日在四川大学华西第二医院产科行产前检查的孕妇，采用前瞻性队列研究的方法，对所有孕妇于孕24～28周时行50 g葡萄糖负荷试验，或75 g葡萄糖耐量试验（ OGTT），随机抽取104例GDM孕妇为GDM组，103例血糖正常的健康孕妇为对照组，采用PCR-序列特异性引物（ PCR-SSP）技术检测两组孕妇的HLA-DRB1基因多态性，采用单纯病例研究方法，将HLA-DRB1基因多态性与GDM危险因素进行基因-环境交互作用分析。结果（1）2011年1月1日-12月31日共纳入资料完整孕妇712例，其中GDM 孕妇175例，血糖正常孕妇537例。多因素回归分析显示，孕妇高龄（≥35岁）、饮食不均衡、孕前高体质指数（ BMI≥24.0 kg／m^2）、携带乙型肝炎病毒（ HBV）、有糖尿病家族史系GDM发病的危险因素。（2）对照组孕妇中共检出51种HLA-DRB1基因型， GDM 组孕妇中共检出49种HLA-DRB1基因型。对GDM组或对照组中出现≥3例的基因型进行比较，HLA-DRB1＊12，16基因型仅在对照组中检出5例（4.9％，5／103），两组比较，差异有统计学意义（ P＝0.029）；而且仅在GDM组中检出4例（3.8％，4／104）HLA-DRB1＊11，16基因型和5例（4.8％，5／104） HLA-DRB1＊09，09基因型，但两组比较，差异均无统计学意义（P＞0.05）；余基因型频率在两组中比较，差异均无统计学意义（P＞0.05）。（3）本研究共检测出13种HLA-DRB1等位基因，GDM组与对照组各HLA-DRB1等位基因频率比较，差异无统计学意义（P＞0.05）。（4）孕妇高龄（≥35岁）与HLA-DRB1基因多态性的交互作用分析表明， HLA-DRB1＊07等位基因与孕妇高龄呈正向交互作用（ OR＝5.952，95％CI为1.314～26.970， P＝0.022）；而携带HBV、糖尿病家族史、孕前BMI≥24.0 kg／m^2、饮食不均衡与HLA-DRB1基因多态性在GDM发病中未发现有交互作用。结论孕妇高龄、饮食不均衡、孕前高BMI、携带HBV、有糖尿病家族史为成都地区GDM发生的危险因素，HLA-DRB1＊12，16可能为GDM的保护基因型，孕妇高龄与HLA-DRB1＊07对GDM的发生存在明显的正向交互作用。
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/m^2） 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/m^2 ） , HBsAg carrier status or DM family history.Conclusions Advanced maternal age, unbalanced diet, high body mass index （BMI≥24.0 kg/m^2）, 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.
出处
《中华妇产科杂志》
CAS
CSCD
北大核心
2014年第4期270-275,共6页
Chinese Journal of Obstetrics and Gynecology
基金
四川省科技厅科技支撑计划（2012SZ0036）
成都市科技局计划项目（10GGYB898SF-023）
