Fetal growth is increased by maternal type 1 diabetes and HLA DR4-related gene interactions

Aims/hypothesis Intrauterine growth in non-diabetic pregnancies is reported to be influenced by type 1 diabetes susceptibility genes. In particular, the high-risk HLA DR4_DQB1*0302 haplotype is associated with increased birthweight. The aim of this study was to determine whether HLA DR4 was associated with increased birthweight in a maternal diabetes environment and whether effects persisted during early childhood. Subjects and methods Birthweight and gestational age were obtained in singleton births from mothers with type 1 diabetes (n = 1161) or whose fathers or siblings have type 1 diabetes (n = 872). Weight and height at ages 2 and 5 years were obtained from paediatric records. Data were adjusted for (gestational) age and sex and expressed as percentiles of German reference data. HLA DR typing was obtained for all children and 1090 children also had insulin gene (INS) variable number of tandem repeats (VNTR) typing. Results Maternal type 1 diabetes was associated with increased birthweight, gestational age and birthweight percentiles (all p < 0.0001). In children of mothers with type 1 diabetes, birthweight percentile was further related to maternal HbA_1c during pregnancy (r = 0.26; p < 0.0001) and was independently increased if children had HLA DR4 alleles (76th vs 64th percentile; p < 0.0001). HLA DR4 was not associated with birthweight in children of non-diabetic mothers. Birthweight was not associated with INS VNTR genotypes. High birthweight, but not HLA DR4 was associated with increased weight and BMI at ages 2 and 5 years (p < 0.0001). Conclusions/interpretation Our findings are consistent with the hypothesis that a diabetic intrauterine environment interacts with gene(s) marked by the type 1 diabetes susceptibility HLA DR4 alleles to increase fetal growth. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorised users.     

eNOS基因多态性与原发性高血压及其脑梗塞易感性的关系

[目的]探讨内皮型一氧化氮合酶(eNOS)基因27 bp数目可变的串联重复序列(VNTR)多态性与原发性高血压(EH)及其脑梗塞易感性的关系.[方法]①采用PCR-琼脂糖凝胶电泳法检测227例EH患者(其中123例无脑梗塞EH(-),104例并发脑梗塞EH( )和145例对照者27 bp VNTR基因型;②硝酸还原酶法测定对照组空腹血清-氧化氮代谢物(NOx)水平.[结果]①EH组aa ab基因型及a等位基因频率高于对照组(基因型0.220/0.083;等位基因0.121/0.041,P值均＜0.01);EH( )组与EH(-)组间基因频率分布类似.以65岁进行年龄分层,EH＜65组aa ab基因型及a等位基因频率高于对照组＜65组(基因型0.256/0.073;等位基因0.140/0.036,P值均＜0.01);EH( )＜65组aa ab基因型及a等位基因频率高于EH(-)＜65组(基因型0.347/0.194;等位基因0.194/0.104,P值均＜0.05).②多因素分析表明,27 bp VNTR多态性是EH发生的独立危险因素,也是65岁以下EH患者发生脑梗塞的独立危险因素.③对照组aa ab基因型空腹血清NOx低于bb基因型(P＜0.05).[结论]①eNOS基因27 bp VNTR多态性可能与原发性高血压及其早发脑梗塞有关;②a等位基因可能通过减少内皮基础NO释放参与上述病变的发生.