妊娠期糖尿病与HLA基因相关性研究
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摘要
目的:
妊娠期糖尿病(gestational diabetes mellitus,GDM)是指妊娠期首次发生或发现的糖代谢异常。近年来,随着医疗诊断技术和人们生活水平的提高,GDM的发病率呈逐年上升的趋势。目前认为糖尿病是一种多基因遗传病,GDM为糖尿病的一个特殊类型,多种基因的相互作用在GDM的发病中起着重要的作用。人类白细胞抗原(human leucocyte antigen,HLA)基因上的某些位点可能与GDM的易感性有关,但至今尚无定论。本研究主要探讨广西地区汉族GDM与HLA-DQA1等位基因的相关性,及HLA-DQA1基因与孕妇血糖,新生儿血糖、体重及Apgar评分的关系。
方法:
选取2006年10月—2007年4月于广西医科大学第一附属医院住院分娩的GDM孕妇50例,随机选取同期入院的正常孕妇50例作为对照。按照WHO诊断标准诊断GDM。采用聚合酶链反应—序列特异性引物(polymerase chain reaction-sequence specific primersm,PCR-SSP)法对50例广西汉族GDM孕妇及50例汉族健康孕妇的HLA-DQA1基因型进行检测。测量孕妇血糖,新生儿的血糖值及体重,对新生儿进行Apgar评分。
结果
GDM组孕妇与对照组孕妇相比较,HLA-DQA1*0501基因频率明显升高(30.0%vs 14.0%),差异有显著性(P=0.006),OR值为2.633。HLA-DQA1*0101,0104,0201,0601等位基因频率在GDM组孕妇中有增高趋势,(其频率分别为9.0%vs 6.0%,11.0%vs 10.0%,3.0%vs 2.0%,6.0%vs 5.0%),但差异没有显著性(P均＞0.05)。而GDM组中HLA-DQA1*0102,0103,0301,0302和0401基因频率有降低趋势,为(20.0%vs 28.0%,3.0%vs 8.0%,9.0%vs 13.0%,0.0%vs 2.0%,9.0%vs 12.0%),差异亦无著性(P均＞0.05)。
GDM组中有19位病人(38%)需要使用胰岛素治疗,47位GDM患者(94%)血糖控制良好,GDM组产后血糖较产前血糖降低(为5.16±0.83mmol/L vs 6.26±0.76mmol/L),差异有显著性(P＜0.05)。GDM组有不良孕产史,高血压病及糖尿病家族史者较对照组明显增加,(分别为18.0%vs 2.0%,12.0%vs 2.0%,28.0%vs 0.0%),差异有显著性(P均＜0.05)。GDM组新生儿体重高于对照组(为3341.6±329.7 g vs3169.4±497.7 g),血糖低于对照组(3.16±0.83 mmol/L vs 5.04±1.63mmol/L),差异有显著性(P均＜0.05)。两组新生儿Apgar 1分钟、10分钟评分的中位数均为10,差异无显著性(P＞0.05)。GDM组孕妇的新生儿中发生巨大儿者有2人(4.0%),对照组有1人(2.0%),差异无显著性(P＞0.05)。GDM组中发生新生儿低血糖症者1人(2.0%),对照组中无新生儿低血糖症发生,差异无显著性(P＞0.05)。GDM组中有2人发生新生儿窒息(4.0%),对照组有2人(4.0%),差异无显著性(P＞0.05)。
GDM组按是否携带HLA-DQA1*0501基因分为携带组与非携带组,两组比较,产前血糖值无明显差异(6.35±0.85 mmol/L vs 6.17±0.68 mmol/L,P＞0.05)。产后血糖值亦无明显差异(为5.42±0.75mmol/L vs 5.49±0.91mmol/L,P＞0.05)。两组中有不良孕产史,高血压病及糖尿病家族史者无显著性差异(分别为26.1%vs 11.1%,4.3%vs 18.5%,39.1%vs 18.5%,P均＞0.05)。两组中产前使用胰岛素率亦无差别(37.0%vs 39.1%,P均＞0.05)。两组新生儿体重及血糖值差异亦无显著性,(为3366.9±346.7g vs3320.0±319.7g,3.28±0.83mmol/L vs 3.01±0.84mmol/L,P均＞0.05)。两组新生儿Apgar 1分钟与10分钟评分中位数均为10,差异无显著性(P＞0.05)。
结论:
HLA-DQA1*0501基因可能为广西地区汉族GDM的易感基因,未发现与HLA-DQA1相关的GDM保护基因。未发现HLA-DQA1*0501基因与孕妇血糖,新生儿血糖、体重及Apgar评分相关。
Objective:
Gestational diabetes mellitus(GDM)is defined as carbohydrate intolerance of varying severity with onset or first recognition during pregnancy.In recent years,as medical diagnostic technology and living standard progress,the morbidity of GDM presents an annual rising trend.At present,diabetes mellitus is considered as a polygenic inherited disease.GDM is a special type of diabetes, multiple genes have a impact on GDM.Some sites in HLA gene may have certain connection to the susceptibility of GDM.However,there is no definitive academic opinion on the connection between HLA gene and GDM.We investigate the association between polymorphism of HLA-DQA1 and susceptibility of gestational diabetes mellitus in Han ethnic of Guangxi,and the association between polymorphism of HLA-DQA1 and the blood glucose of the GDM pregnant women and the blood glucose,weights,Apgar scores of their newborns.
Methods:
This study enrolled 50 cases of GDM and 50 cases of normal pregnant women in the First affiliated Hospital of Guangxi medical university during October,2006 to April,2007,excluded diseases correlated with HLA gene. GDM was diagnosed by WHO standard.PCR-SSP gene typing technique was used to detect HLA-DQA1 alleles.Record the blood glucose of the GDM pregnant women and the blood glucose,weights,Apgar scores of their newborns.
Results:
It was observed that gene frequency of HLA-DQA1~*0501 increased in GDM group compared with control group(30%vs 14.0%,P=0.006).OR is 2.633.We also observed that the gene frequencies of HLA-DQA1~*0101,0104, 0201 and 0601 gene were incresed in GDM group,but have no significant difference(9.0%vs 6.0%,11.0%vs 10.0%,3.0%vs 2.0%,6.0%vs 5.0%, P＞0.05).The gene frequencies of HLA-DQA1~*0102,0103,0301,0302 and 0401 were decreased in GDM group,but also have no significant difference (20.0%vs 28.0%,3.0%vs 8.0%,9.0%vs 13%,0.0%vs 2.0%,9.0%vs 12.0%, P＞0.05).
19 GDM patiens(38%)need insulin therapy.The blood glucose of 47 GDM patiens(94%)control well.In GDM group,the postpartum blood glucose decresed compared with the antepartum(5.16±0.83mmol/L vs 6.26±0.76mmol/L,P＜0.05).The incidence of bad outcomes in previous gestation and delivery,and the familiy history of high blood pressure and diabetes mellitus in GDM group was higher than the control group(18.0%vs 2.0%,12.0%vs 2.0%,28.0%vs 0.0%,P＜0.05).The weight of newborns of GDM group much higher than control group(3341.6±329.7g vs 3169.4±497.7g, P＜0.05).And the blood glucose of newborn lower than control group(3.16±0.83 mmol/L vs 5.04±1.63mmol/L,P＜0.05).The median of Apgar score in two groups were both 10,have no significant difference(P＞0.05).Large for date infant was two in GDM group(4.0%),while one in control group(2.0%, P＞0.05).One in GDM group had neonatal hypoglycemia(2.0%),none in control group(P＞0.05).Apnoea neonatorum was two in GDM group(4.0%),and two in control group(4.0%),also have no significant difference(P＞0.05).
Divided GDM group into two groups,one group have HLA-DQA1~*0501, another didn't have.The postpartum blood glucose and the antepartum in two groups have no significant difference(6.35±0.85 mmol/L vs 6.17±0.68 mmol/L, 5.42±0.75mmol/L vs 5.49±0.91 mmol/L,P＞0.05).The incidence of bad outcomes during previous gestation and delivery,the familiy history of high blood pressure and diabetes mellitus,needed insulin to cure have no difference (26.1%vs 11.1%,4.3%vs 18.5%,39.1%vs 18.5%,37.0%vs 39.1%,P＞0.05). The weight,blood glucose and the Apgar score of newborn in two groups also have no significant difference(3366.9±346.7g vs 3320.0±319.7g,3.28±0.83 mmol/L vs 3.01±0.84 mmol/L,10 vs 10,P＞0.05).
Conclusions:
Alleles HLA-DQA1~*0501 may be the susceptible gene of GDM in Han ethnic of Guangxi,but the protective gene of GDM is still not found.The association between HLA-DQA1~*0501 and the glucose of pregnant women,the weight,blood glucose and Apgar score of newborns is also not found.
妊娠期糖尿病(gestational diabetes mellitus,GDM)是指妊娠期首次发生或发现的糖代谢异常。近年来,随着医疗诊断技术和人们生活水平的提高,GDM的发病率呈逐年上升的趋势。目前认为糖尿病是一种多基因遗传病,GDM为糖尿病的一个特殊类型,多种基因的相互作用在GDM的发病中起着重要的作用。人类白细胞抗原(human leucocyte antigen,HLA)基因上的某些位点可能与GDM的易感性有关,但至今尚无定论。本研究主要探讨广西地区汉族GDM与HLA-DQA1等位基因的相关性,及HLA-DQA1基因与孕妇血糖,新生儿血糖、体重及Apgar评分的关系。
方法:
选取2006年10月—2007年4月于广西医科大学第一附属医院住院分娩的GDM孕妇50例,随机选取同期入院的正常孕妇50例作为对照。按照WHO诊断标准诊断GDM。采用聚合酶链反应—序列特异性引物(polymerase chain reaction-sequence specific primersm,PCR-SSP)法对50例广西汉族GDM孕妇及50例汉族健康孕妇的HLA-DQA1基因型进行检测。测量孕妇血糖,新生儿的血糖值及体重,对新生儿进行Apgar评分。
结果
GDM组孕妇与对照组孕妇相比较,HLA-DQA1*0501基因频率明显升高(30.0%vs 14.0%),差异有显著性(P=0.006),OR值为2.633。HLA-DQA1*0101,0104,0201,0601等位基因频率在GDM组孕妇中有增高趋势,(其频率分别为9.0%vs 6.0%,11.0%vs 10.0%,3.0%vs 2.0%,6.0%vs 5.0%),但差异没有显著性(P均＞0.05)。而GDM组中HLA-DQA1*0102,0103,0301,0302和0401基因频率有降低趋势,为(20.0%vs 28.0%,3.0%vs 8.0%,9.0%vs 13.0%,0.0%vs 2.0%,9.0%vs 12.0%),差异亦无著性(P均＞0.05)。
GDM组中有19位病人(38%)需要使用胰岛素治疗,47位GDM患者(94%)血糖控制良好,GDM组产后血糖较产前血糖降低(为5.16±0.83mmol/L vs 6.26±0.76mmol/L),差异有显著性(P＜0.05)。GDM组有不良孕产史,高血压病及糖尿病家族史者较对照组明显增加,(分别为18.0%vs 2.0%,12.0%vs 2.0%,28.0%vs 0.0%),差异有显著性(P均＜0.05)。GDM组新生儿体重高于对照组(为3341.6±329.7 g vs3169.4±497.7 g),血糖低于对照组(3.16±0.83 mmol/L vs 5.04±1.63mmol/L),差异有显著性(P均＜0.05)。两组新生儿Apgar 1分钟、10分钟评分的中位数均为10,差异无显著性(P＞0.05)。GDM组孕妇的新生儿中发生巨大儿者有2人(4.0%),对照组有1人(2.0%),差异无显著性(P＞0.05)。GDM组中发生新生儿低血糖症者1人(2.0%),对照组中无新生儿低血糖症发生,差异无显著性(P＞0.05)。GDM组中有2人发生新生儿窒息(4.0%),对照组有2人(4.0%),差异无显著性(P＞0.05)。
GDM组按是否携带HLA-DQA1*0501基因分为携带组与非携带组,两组比较,产前血糖值无明显差异(6.35±0.85 mmol/L vs 6.17±0.68 mmol/L,P＞0.05)。产后血糖值亦无明显差异(为5.42±0.75mmol/L vs 5.49±0.91mmol/L,P＞0.05)。两组中有不良孕产史,高血压病及糖尿病家族史者无显著性差异(分别为26.1%vs 11.1%,4.3%vs 18.5%,39.1%vs 18.5%,P均＞0.05)。两组中产前使用胰岛素率亦无差别(37.0%vs 39.1%,P均＞0.05)。两组新生儿体重及血糖值差异亦无显著性,(为3366.9±346.7g vs3320.0±319.7g,3.28±0.83mmol/L vs 3.01±0.84mmol/L,P均＞0.05)。两组新生儿Apgar 1分钟与10分钟评分中位数均为10,差异无显著性(P＞0.05)。
结论:
HLA-DQA1*0501基因可能为广西地区汉族GDM的易感基因,未发现与HLA-DQA1相关的GDM保护基因。未发现HLA-DQA1*0501基因与孕妇血糖,新生儿血糖、体重及Apgar评分相关。
Objective:
Gestational diabetes mellitus(GDM)is defined as carbohydrate intolerance of varying severity with onset or first recognition during pregnancy.In recent years,as medical diagnostic technology and living standard progress,the morbidity of GDM presents an annual rising trend.At present,diabetes mellitus is considered as a polygenic inherited disease.GDM is a special type of diabetes, multiple genes have a impact on GDM.Some sites in HLA gene may have certain connection to the susceptibility of GDM.However,there is no definitive academic opinion on the connection between HLA gene and GDM.We investigate the association between polymorphism of HLA-DQA1 and susceptibility of gestational diabetes mellitus in Han ethnic of Guangxi,and the association between polymorphism of HLA-DQA1 and the blood glucose of the GDM pregnant women and the blood glucose,weights,Apgar scores of their newborns.
Methods:
This study enrolled 50 cases of GDM and 50 cases of normal pregnant women in the First affiliated Hospital of Guangxi medical university during October,2006 to April,2007,excluded diseases correlated with HLA gene. GDM was diagnosed by WHO standard.PCR-SSP gene typing technique was used to detect HLA-DQA1 alleles.Record the blood glucose of the GDM pregnant women and the blood glucose,weights,Apgar scores of their newborns.
Results:
It was observed that gene frequency of HLA-DQA1~*0501 increased in GDM group compared with control group(30%vs 14.0%,P=0.006).OR is 2.633.We also observed that the gene frequencies of HLA-DQA1~*0101,0104, 0201 and 0601 gene were incresed in GDM group,but have no significant difference(9.0%vs 6.0%,11.0%vs 10.0%,3.0%vs 2.0%,6.0%vs 5.0%, P＞0.05).The gene frequencies of HLA-DQA1~*0102,0103,0301,0302 and 0401 were decreased in GDM group,but also have no significant difference (20.0%vs 28.0%,3.0%vs 8.0%,9.0%vs 13%,0.0%vs 2.0%,9.0%vs 12.0%, P＞0.05).
19 GDM patiens(38%)need insulin therapy.The blood glucose of 47 GDM patiens(94%)control well.In GDM group,the postpartum blood glucose decresed compared with the antepartum(5.16±0.83mmol/L vs 6.26±0.76mmol/L,P＜0.05).The incidence of bad outcomes in previous gestation and delivery,and the familiy history of high blood pressure and diabetes mellitus in GDM group was higher than the control group(18.0%vs 2.0%,12.0%vs 2.0%,28.0%vs 0.0%,P＜0.05).The weight of newborns of GDM group much higher than control group(3341.6±329.7g vs 3169.4±497.7g, P＜0.05).And the blood glucose of newborn lower than control group(3.16±0.83 mmol/L vs 5.04±1.63mmol/L,P＜0.05).The median of Apgar score in two groups were both 10,have no significant difference(P＞0.05).Large for date infant was two in GDM group(4.0%),while one in control group(2.0%, P＞0.05).One in GDM group had neonatal hypoglycemia(2.0%),none in control group(P＞0.05).Apnoea neonatorum was two in GDM group(4.0%),and two in control group(4.0%),also have no significant difference(P＞0.05).
Divided GDM group into two groups,one group have HLA-DQA1~*0501, another didn't have.The postpartum blood glucose and the antepartum in two groups have no significant difference(6.35±0.85 mmol/L vs 6.17±0.68 mmol/L, 5.42±0.75mmol/L vs 5.49±0.91 mmol/L,P＞0.05).The incidence of bad outcomes during previous gestation and delivery,the familiy history of high blood pressure and diabetes mellitus,needed insulin to cure have no difference (26.1%vs 11.1%,4.3%vs 18.5%,39.1%vs 18.5%,37.0%vs 39.1%,P＞0.05). The weight,blood glucose and the Apgar score of newborn in two groups also have no significant difference(3366.9±346.7g vs 3320.0±319.7g,3.28±0.83 mmol/L vs 3.01±0.84 mmol/L,10 vs 10,P＞0.05).
Conclusions:
Alleles HLA-DQA1~*0501 may be the susceptible gene of GDM in Han ethnic of Guangxi,but the protective gene of GDM is still not found.The association between HLA-DQA1~*0501 and the glucose of pregnant women,the weight,blood glucose and Apgar score of newborns is also not found.
引文
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[31]赵曼林,冯玉昆,祁文瑾,人类白细胞抗原Ⅱ类基因与GDM的相关性研究,中华妇产科杂志,2005,40(10),673
[32]龙桂芳,阿卜迪,李卫,应用序列特异引物PCR法对广西壮族HLA-DQA1进行基因分型,中华血液学杂志,1995,16(10),532-534
[1]Cypryk K,Pertynska-Marczewska M,Szymczak W,et al.Overweight and obesity as common risk factors for gestational diabetes mellitus (GDM),perinatal macrosomy in offspring and type-2 diabetes in mothers.Przegl Lek,2005,62(1):38-41.
[2]Akbay E,TirasMB,Yetkin I,et al.Insulin secretion and insulin sensitivity in normal pregnancy and gestatioal diabetesmellitus.Gynecol Endocrinol,2003,17(2):137.
[3]Bomba-Opon D,Wielgos M,Szymanska M,et al.Effects of free fatty acids on the course of gestational diabetes mellitus.Neuro Endocrinol Lett,2006,27(-2):277-280.
[4] Qiu C,Williams MA,Vadachkoria S,et al.Increased maternal plasma leptin in early pregnancy and risk of gestational diabetes mellitus.Obstet Gynecol,2004,103(3):519-525.
[5] Weerakiet S,Lertnarkorn K,Panburana P,et al.Can adiponectin predict gestational diabetes? Gynecol Endocrinol,2006,22(7):362-368.
[6] John P,Thyfault PhD,Elizabet h M,et al.Gestation diabetes is associated with depressed adiponectin levels.J Soci Gynecol Invest,2005,12 :41-45.
[7] Tsai PJ,Yu CH,Hsu SP,et al.Maternal plasma adiponectin concentrations at 24 to 31 weeks of gestation: negative association with gestational diabetes mellitus.Nutrition,2005,21(11-12):1095-1099.
[8] KinalskiM,Telejko B,KuzmickiM,et al.Tumor necrosis factor alpha system and plasma adiponectin concentration in women with gestational diabetes.Horm Metab Res,2005,37(7):450-454.
[9] Buchanan TA,Xiang AH.Gestational diabetes mellitus.J Clin Invest,2005,115:485-491.
[10] Bachaf,Saadr,Guogor,et aLAdiponectin in youth:relationship to visceral adiposity,insulin sensitivity,and beta cell function.Diabetes care,2004,27:547-552.
[11] Retnakaran R,Hanley AJ.Raif NAdiponectin and beta cell dysfunction in gestational diabetes: pathophysiological implications.Diabetologia,2005,48(5):993-1001.
[12] Radaelli T,Varastehpour A,Catalano P. et al.Gestational diabetes induces lacental genes for chronic stress and inflammatory pathways.Diabetes,2003,52(12):2951-2958.
[13] Bo S,Signorile A,MenatoG,et al.C-reactive protein and tumor necrosis factor-alpha in gestational hyperglycemia.J Endocrinol Invest,2005,28(9):779-786.
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[15] Qiu C,Sorensen TK,Luthy DA,et al.Paediatr Perinat Epidemiol. A prospective study of maternal serum c-reactive protein (CRP) concentrations and risk of gestational diabetes mellitus. Paediatr Perinat Epidemiol,2004,18(5):377-384.
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[18] Mahmoud FF,Haines DD.Abul HT Butyrylcholinesterase activity in gestational diabetes: correlation with lymphocyte subpopulations in peripheral blood. Am J Reprod Immunol,2006,56(3):185-192.
[19] Torn C,Gupta M,Sanjeevi CB,et al. Different HLA-DR-DQ and MHC class I chain-related gene A (MICA)genotypes in autoimmune and nonautoimmune gestational diabetes in a Swedish population.Hum Immunol,2004,65:1443-1450.
[20]Tomoatsu N,Alexandria.HLA-DR-DQ haplotype in rapidonset type 1diabetes in Janpaese.Diabetes Care,2003,26:1640-1642.
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[30]牛秀敏,常征,常颖,GDM与HLA-DQA1基因多态性相关性的研究,天津医科大学学报,2006,12(2),211-213
[31]赵曼林,冯玉昆,祁文瑾,人类白细胞抗原Ⅱ类基因与GDM的相关性研究,中华妇产科杂志,2005,40(10),673
[32]龙桂芳,阿卜迪,李卫,应用序列特异引物PCR法对广西壮族HLA-DQA1进行基因分型,中华血液学杂志,1995,16(10),532-534
[1]Cypryk K,Pertynska-Marczewska M,Szymczak W,et al.Overweight and obesity as common risk factors for gestational diabetes mellitus (GDM),perinatal macrosomy in offspring and type-2 diabetes in mothers.Przegl Lek,2005,62(1):38-41.
[2]Akbay E,TirasMB,Yetkin I,et al.Insulin secretion and insulin sensitivity in normal pregnancy and gestatioal diabetesmellitus.Gynecol Endocrinol,2003,17(2):137.
[3]Bomba-Opon D,Wielgos M,Szymanska M,et al.Effects of free fatty acids on the course of gestational diabetes mellitus.Neuro Endocrinol Lett,2006,27(-2):277-280.
[4] Qiu C,Williams MA,Vadachkoria S,et al.Increased maternal plasma leptin in early pregnancy and risk of gestational diabetes mellitus.Obstet Gynecol,2004,103(3):519-525.
[5] Weerakiet S,Lertnarkorn K,Panburana P,et al.Can adiponectin predict gestational diabetes? Gynecol Endocrinol,2006,22(7):362-368.
[6] John P,Thyfault PhD,Elizabet h M,et al.Gestation diabetes is associated with depressed adiponectin levels.J Soci Gynecol Invest,2005,12 :41-45.
[7] Tsai PJ,Yu CH,Hsu SP,et al.Maternal plasma adiponectin concentrations at 24 to 31 weeks of gestation: negative association with gestational diabetes mellitus.Nutrition,2005,21(11-12):1095-1099.
[8] KinalskiM,Telejko B,KuzmickiM,et al.Tumor necrosis factor alpha system and plasma adiponectin concentration in women with gestational diabetes.Horm Metab Res,2005,37(7):450-454.
[9] Buchanan TA,Xiang AH.Gestational diabetes mellitus.J Clin Invest,2005,115:485-491.
[10] Bachaf,Saadr,Guogor,et aLAdiponectin in youth:relationship to visceral adiposity,insulin sensitivity,and beta cell function.Diabetes care,2004,27:547-552.
[11] Retnakaran R,Hanley AJ.Raif NAdiponectin and beta cell dysfunction in gestational diabetes: pathophysiological implications.Diabetologia,2005,48(5):993-1001.
[12] Radaelli T,Varastehpour A,Catalano P. et al.Gestational diabetes induces lacental genes for chronic stress and inflammatory pathways.Diabetes,2003,52(12):2951-2958.
[13] Bo S,Signorile A,MenatoG,et al.C-reactive protein and tumor necrosis factor-alpha in gestational hyperglycemia.J Endocrinol Invest,2005,28(9):779-786.
[14] Rota S,Yildirim B,Kaleli B,et al.C-reactive protein levels in non-obese pregnant women with gestational diabetes.Tohoku J Exp Med,2005,206(4):341-345.
[15] Qiu C,Sorensen TK,Luthy DA,et al.Paediatr Perinat Epidemiol. A prospective study of maternal serum c-reactive protein (CRP) concentrations and risk of gestational diabetes mellitus. Paediatr Perinat Epidemiol,2004,18(5):377-384.
[16] Wolf M,Sauk J,Shah A,et al. Inflammation and glucose intolerance: a prospective study of gestational diabetes mellitus.Diabetes Care,2004,27(1):21-27.
[17] Mahmoud F,Abul H,Omu A,et al.Lymphocyte sub-populations in gestational diabetes.Am J Reprod Immunol,2005,53:21-29.
[18] Mahmoud FF,Haines DD.Abul HT Butyrylcholinesterase activity in gestational diabetes: correlation with lymphocyte subpopulations in peripheral blood. Am J Reprod Immunol,2006,56(3):185-192.
[19] Torn C,Gupta M,Sanjeevi CB,et al. Different HLA-DR-DQ and MHC class I chain-related gene A (MICA)genotypes in autoimmune and nonautoimmune gestational diabetes in a Swedish population.Hum Immunol,2004,65:1443-1450.
[20]Tomoatsu N,Alexandria.HLA-DR-DQ haplotype in rapidonset type 1diabetes in Janpaese.Diabetes Care,2003,26:1640-1642.