1型糖尿病种HLA-DQA1-DQB1连锁基因的特征研究

目的：探讨HLA-DQA1-DQB1连锁基因单倍体与成人缓慢进展型1型糖尿病（SPIDDM）和速发型1型糖尿病（FPIDDM）的相关性。方法：采用PCR/SSP技术检测本组1型糖尿病中102例SPIDDM患者和130例FPIDDM患者频率。结果：①HLA-DQA1＊0301-DQB1＊0201和DQA1＊0501-DQB1＊0201连锁基因单倍体与SPIDDM（Pc〈0.001）和FPIDDM（Pc〈0.001）均呈显著正相关。②HLA-DQA1＊0301-DQB1＊0301和DQA1＊0301-DQB1＊0602连锁基因单倍体与SPIDDM呈显著正相关（Pc〈0.001）。③HLA-DQA1＊0301-DQB1＊0302、DQA1＊0301-DQB1＊0303及DRB1＊0301-DQA1＊0301-DQB1＊0201连锁基因单倍体与FPIDDM呈显著正相关（均Pc〈0.05）;DQA1＊0102等位基因中SPIDDM组16例（15.69%）;FPIDDM组10例（7.69%）（P〈0.05）;DQA1＊03基因SPIDDM组47例（46.08%）,FPIDDM组79例（60.77%）（P〈0.05）;DQB1＊0601基因SPIDDM组10例（9.8%）,FPIDDM组4例（3.08%）（P〈0.01）。结论：SPIDDM和FPIDDM虽然均为自身免疫性糖尿病,但其HLA表型并不完全相同,不同的HLA表型可能是决定患者起病方式及病情发展不同的因素之一。     

1型糖尿病与HLA-DRB1?DQB1基因相关性研究

目的: 研究中国江苏地区汉族人群1型糖尿病(T1DM)与人类白细胞抗原(HLA)-DRB1?DQB1基因及单倍型频率的相关性?方法:选取江苏地区汉族人群T1DM患者(112例)与对照组(69例),运用聚合酶链反应-寡核苷酸探针序列特异性引物(PCR-SSO)技术,进行HLA-DRB1?DQB1基因分型,两组间等位基因频率比较采用χ2检验,通过Arlequin软件进行单倍型频率的分析?结果:112名T1DM患者中检测到DRB1位点等位基因17个(对照组19个),DQB1位点等位基因7个(对照组7个)?与对照组相比,T1DM组DRB1*0901?DRB1*0405和DRB1*0301频率明显增高,DQB1位点的DQB1*0201与DQB1*0303频率明显高于对照组;与对照组相比,T1DM患者明显升高的单倍型频率为:DRB1*0901-DQB1*0303?DRB1*0301-DQB1*0201?DRB1*0405-DQB1*0401和DRB1*0405-DQB1*0302?结论:中国江苏地区汉族T1DM患者HLA基因DR位点的DRB1*0901?DRB1*0405?DRB1*0301及DQ位点的DQB1*0201?DQB1*0303对T1DM易感?发现了4个新的具有易感作用的单倍型:DRB1*0901-DQB1*0303?DRB1*0301-DQB1*0201?DRB1*0405-DQB1*0401和DRB1*0405 -DQB1*0302?     

江苏汉族人HLA-DQ位点基因多态性分析

用聚合酶链反应结合顺序持异的寡核苷酸t（PCR／SSO）探针杂交方法分析了86例江苏籍汉族正常人HLA－DQ位点等位基因分布情况，发现大多数DQA1和DQB1等位基因阳性，并与白种人的不同。证实了HLA分布的种族差异，研究结果对于探索人类的起源和人数的迁移与进化有重要意义。     

HLA-DQA1基因与广西地区2型糖尿病关联性的研究

目的:探讨2型糖尿病(DM)及其并发症与HLA的相关情况.方法:采用聚合酶链反应-序列特异性引物(PCR-SSP)法对72名广西汉族2型糖尿病(DM)及46名汉族正常对照的HLA-DQA1位点进行基因分型.结果:2型DM组DQA1*0401等位基因频率明显低于正常对照组,DOA1*0104等位基因频率明显高于正常对照组,2型DM并肾病组和并高血压组DQA1*0501等位基因频率分别低于无肾病组和无高血压组.结论:广西汉族2型DM及其并发症与HLA有关联;HLA-DQA1*0401可能为2型DM的保护基因,HLA-DQA1*0104可能为2型DM的易感基因;HLA-DQA1*0501对2型DM并肾病、高血压具有保护作用.     

INSIG1基因SNPrs9769506位点的多态性与2型糖尿病的关系

目的：探讨胰岛素诱导基因1（INSIG1）单核苷酸多态性（SNP）rs9769506位点的多态性与2型糖尿病（T2DM）的相关性,以期为 T2DM 的防治提供潜在的分子靶点。方法选择河南省南阳市中心医院2013年1月至2014年3月收治的 T2DM患者98例,另选取体检中心的健康体检者90例作为对照组,INSIG1基因 SNP rs9769506位点多态性检测使用实时荧光定量PCR（RT‐PCR）Taqman 分析。结果 T2DM 组 rs9769506位点 A 等位基因频率为54．1％,G 等位基因频率为45．9％,对照组 A等位基因频率为47．8％,G 等位基因频率为52．2％,两组之间差异无统计学意义（P ＞0．05）。 T2DM 组患者 rs9769506位点 A/A 、A /G 和 G/G 基因型频率分别为41．8％、24．5％和33．7％,对照组 rs9769506位点 A/A 、A/G 和 G/G 基因型频率分别为32．2％、31．1％和36．7％,A/A 基因型频率在对照组和 T2DM 组之间差异有统计学意义（P＜0．05）,而 A/G 和 G/G 基因型频率在对照组和 T2DM 组之间差异则无统计学意义（P＞0．05）。 T2DM 患者中三酰甘油（TG）、总胆固醇（TC）、低密度脂蛋白胆固醇（LDL‐C）、高密度脂蛋白胆固醇（HDL‐C）表达水平在 A /A 、A/G 、G/G 基因型患者之间差异有统计学意义（P ＜0．05）,而 A/G 、G/G 基因型患者之间差异无统计学意义（P＞0．05）。结论 INSIG1基因 SNP rs9769506位点 A/A 基因型在 T2DM 患者中检出率高,对 T2DM 早期筛查及基因治疗具有临床指导意义。     

广东省汉族1型糖尿病患者HLA-DRB1基因多态性分析

目的 探讨HLA-DRB1基因多态性在广东汉族1型糖尿病(T1DM)患者中的分布规律及相关性.方法 采用PCR-SBT技术对58例1型糖尿病患者和454例正常对照人群进行HLA-DRB1等位基因分型.结果 在HLA-DRB1基因位点上,T1DM组和正常对照组共检出38种等位基因.与正常对照组相比,T1DM组的DRB1*0301、DRB1*0405、DRB1*0701、DRB1*0901频率明显升高,而DRB1*1202、DRB1*1502、DRB1*1602频率明显下降,差异有统计学意义(P＜0.05).结论 HLA-DRB1位点上的DRB1*0301、DRB1*0405、DRB1*0701、DRB1*0901是广东汉族人群1型糖尿病的易感基因,而DRB1*1202、DRB1*1502、DRB1*1602为保护基因.     

儿童1型糖尿病54例临床分析

儿童糖尿病绝大多数属 1型糖尿病 ,病因尚未完全阐明 ,但目前认为 ,其发病可能与遗传、环境因素和自身免疫异常有关。我们对住院的 5 4例儿童 1型糖尿病患者的临床资料进行回顾性总结 ,据其发病特点及环境、遗传因素对其发病的影响作一分析 ,以提高对该病的认识。1　资料与方法1 1　一般资料 :1985～ 1999年共收治儿童 1型糖尿病患者5 4例 ,占同期住院儿童糖尿病患者 (75例 )的 72 0 % ,其中男 33例 ,女 2 1例 ,男女比例 1 5 7∶1,起病年龄最小 2 0个月 ,最大 16岁 ,平均年龄 9 18± 6 2 4岁 ,高发年龄以 5～ 7岁和 10～ 13岁 2组。1 2　…     

如何区分1型糖尿病与2型糖尿病

1997年美国糖尿病学会（ADA）将糖尿病分为以下四型：1型糖尿病、2型糖尿病、特异型糖尿病、妊娠糖尿病。在我国，最常见的是2型糖尿病，其次是1型糖尿病。这两种类型有下列主要临床特征（如图）：     

1型糖尿病患者胰岛自身抗体与人类白细胞抗原-DQ基因型的关系

目的 探讨急性起病1型糖尿病（T1DM）患者谷氨酸脱羧酶抗体（GADA）、蛋白酪氨酸磷酸酶抗体（IA-2A）、胰岛素自身抗体（IAA）与人类白细胞抗原（HLA-DQ）基因型之间的关系。方法采用横断面、病例对照研究方法,495例T1DM患者与376例正常对照用放射配体法检测GADA和IA-2A,其中使用胰岛素在2周以内的71例患者与300例正常对照检测IAA。187例抗体阳性、151例抗体阴性T1DM患者与278例正常对照采用PCR直接测序法确定HLA-DQ基因型。结果（1）与正常对照比较,T1DM患者（n=187）DQA1＊03-DQB1＊0303、DQA1＊05-DQB1＊0201与DQA1＊03-DQB1＊0401单体型频率增高（分别为32．6％vs21．9％,14．1％vs3．5％与10．2％vs2．9％,均P〈0．01）,DQA1＊0102-DQB1＊0602单体型频率降低（1.7％vs5．3％,P〈0．05）,而DQA1＊03-DQB1＊0302频率差异无统计学意义（4．7％vs3．8％,P〉0．05）。（2）在338例T1DM患者中,携带DQA1＊05-DQB1＊0201与DQA1＊03-DQB1＊0401单体型患者,GADA阳性率高于不携带此单体型者（分别为55．8％vs41．0％与65．5％vs40．3％,P〈0．05或P〈0．01）;携带DQA1＊03-DQB1＊0303单体型患者IA-2A阳性率高于不携带此单体型者（27．0％vs7．9％,P〈0．01）;携带DQA1＊03-DQB1＊0302单体型患者GADA与IA-2A阳性率分别与不携带此单体型者比较,差异均无统计学意义（48．5％vs43．9％与24．2％vs15．4％,P〉0．05）;而携带保护性DQA1＊0102-DQB1＊0602单体型患者GADA阳性率低于不携带此单体型者（16．7％vs45．9％,P〈0．05）。携带易感单体型者IAA检出率与不携带者比较,差异均无统计学意义（P〉0．05）。结论1型糖尿病患者GADA与DQA1＊05-DQB1＊0201、DQA1＊03-BQB1＊0401单体型相关,IA-2A与DQA1＊03-DQB1＊0303单体型相关。     

HLA-DQB1基因多态性与2型糖尿病的关系

目的:探讨中国北方汉族人HLA-DQB1等位基因多态性与2型糖尿病的关系.方法:采用PCR技术和限制性内切酶片段长度多态性分析方法对49例2型糖尿病患者及55例正常对照者进行了HLA-DQB1基因分析.结果:病例组和对照组HLA-DQB1基因突变型等位基因(G)频率在病例组和对照组间差异无显著性(χ2=0.36, P>0.05),GG、GC 、CC三种基因型出现频率差异无显著性.基因型频率的相对风险分析结果表明 GC基因型与CC基因型患2型糖尿病风险度为1.02, GG基因型与CC基因型患2型糖尿病风险度为0.43.结论:HLA-DQB1基因突变型等位基因与2型糖尿病发病无必然的联系,突变基因型并没有增加2型糖尿病的发病风险.     

Myopia in young patients with type 1 diabetes mellitus

INTRODUCTION

This study aimed to evaluate the proportion of young patients with type 1 diabetes mellitus (T1DM) who have myopia, as well as the risk factors associated with myopia in this group.

METHODS

In this cross-sectional study, patients aged < 21 years with T1DM for ≥ 1 year underwent a comprehensive eye examination. Presence of parental myopia, and average hours of near-work and outdoor activity were estimated using a questionnaire. Annualised glycosylated haemoglobin (HbA1c), defined as the mean of the last three HbA1c readings taken over the last year, was calculated. Multivariate analysis using genetic, environmental and diabetes-related factors was done to evaluate risk factors associated with myopia.

RESULTS

Of the 146 patients (mean age 12.5 ± 3.6 years) recruited, 66.4% were Chinese and 57.5% were female. Myopia (i.e. spherical equivalent [SE] of –0.50 D or worse) was present in 96 (65.8%) patients. The proportion of patients with myopia increased from 25.0% and 53.6% in those aged < 7.0 years and 7.0–9.9 years, respectively, to 59.2% and 78.4% in those aged 10.0–11.9 years and ≥ 12.0 years, respectively. Higher levels of SE were associated with lower parental myopia (p = 0.024) and higher annualised HbA1c (p = 0.011).

CONCLUSION

Compared to the background population, the proportion of myopia in young patients with T1DM was higher in those aged < 10 years but similar in the older age group. Myopia was associated with a history of parental myopia. Environmental risk factors and poor glycaemic control were not related to higher myopia risk.     

HLA-DQ A1, -DQB1 and -DRB1 gene polymorphism--in Malay type 1 diabetes mellitus patients and their use for risk prediction

HLA-DQA1, -DQB1, and -DRB1 gene polymorphism were analyzed to study type 1 DM susceptibility in Malay patients from Southeast Asia (Malaysia and Singapore). Patients showed significant increases in the occurrence of DQA1*0501 (50.7% vs. 20.4%; RR = 3.97; Pc < 0.01), DQB1*0201 (48% vs. 19.1%; RR = 3.86; Pc < 0.05), and DRB1*0301 (38.7 vs. 6.8%; RR = 8.36; 95% Pc < 0.05). Conversely, significant decreases were noted in the occurrence of DQA1*0601 (14.7% vs. 35.2%; RR = 0.33; Pc = 0.008) and DQB1*0601 (4% vs. 23.5%; RR = 0.16; Pc < 0.05) in type 1 DM patients. Using a logistic regression model, we derived a risk prediction model for type 1 DM in our indigenous Malay population based on the identified HLA genotypes. The RR for type 1 DM increases by a factor of 5.68 for every unit increase in the number of DRB1*0301 allele (P < 0.001), and decreases by a factor of 0.18 per unit increase in the number of DQB1*0601 allele (P < 0.001). After adjusting for these two HLA genotypes, DQA1*0501, DQB1*0201 and DQA1*0601 were not statistically significant as risk predictors. The lower incidence of type 1 DM in the Malay population may be contributed by the genotypic combinations of DR and DQ genes as well as the linkage disequilibria between susceptible and protective alleles.     

抵抗素-420C/G基因多态性与中国东北地区汉族人群2型糖尿病大血管病变相关性分析

目的:研究中国东北地区汉族人群抵抗素(RETN)-420C/G基因单核苷酸多态性(SNPs)的等位基因、基因型频率分布及其与2型糖尿病(T2DM)大血管病变之间的关系.方法:应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法对180例样本[T2DM并发大血管病变组60例,单纯T2DM组60例,正常对照(ND...     

A case of Klinefelter’s syndrome with type 1 diabetes mellitus

Klinefelter’s syndrome (KS) is the most common sex chromosome disease in men. Classical features of the syndrome include a eunuchoidal body habitus, small testes and hypergonadotrophic hypogonadism. There has been an increased risk of diabetes mellitus and autoimmune disease for KS patients. This paper reports a case of KS in association with type 1 diabetes mellitus. The patient was a 21-year-old man, who has been confirmed by absolute insulin deficiency and positive IA-2 autoantibody. The hyperinsulinemic euglycemic clamp test indicated his insulin sensitivity in normal range, and his blood glucose was controlled well by the insulin therapy.

     

Acute renal failure in patients with type 1 diabetes mellitus.

Acute renal failure (ARF) is a serious condition which still carries a mortality of around 50%. People with diabetes may be at increased risk of developing ARF, either as a complication of diabetic ketoacidosis or hyperosmolar coma, increased incidence of cardiovascular disease, or due to increased susceptibility of the kidney to adverse effects in the presence of underlying diabetic renal disease. During the period 1956-1992, 1,661 cases of ARF have been treated at Leeds General Infirmary. Of these, we have identified 26 patients also having type 1 diabetes. ARF due to diabetic ketoacidosis is surprisingly uncommon (14 cases out of 23 patients whose notes were reviewed). All cases of ARF complicating ketoacidosis in the last decade have been associated with particularly severe illness requiring intensive care unit support, rather than otherwise ''uncomplicated'' ketoacidosis. We discuss the conditions that may result in ARF in patients with diabetes and the particular difficulties that may be encountered in management.