T 淋巴细胞毒相关抗原-４基因49位点多态性与儿童1型糖尿病相关性的Meta分析

目的：评价T 淋巴细胞毒相关抗原-4（CTLA-4）基因49位点多态性与儿童1型糖尿病（T1DM）的相关性。方法：检索PubMed、EBSCO、中国学术期刊全文数据库（CNKI）、中国生物医学文献数据库（CBM）、万方数据库,收集CTLA-4基因49位点多态性与儿童T1DM相关性的文献。用Meta分析的方法检测CTLA-4基因49位点的基因型和等位基因在儿童T1DM组与对照组中是否有差异。结果：共纳入10篇文献,共有T1DM 1084例,对照组1338例。根据各项研究的异质性检验结果,均利用固定效应模型对CTLA-4基因49位点的AG、GG、GG+AG基因型和G等位基因与T1DM相关性进行Meta分析,各项研究的合并OR值（95% CI）分别为1.13（0.97～1.33）、1.42（1.16～1.75）、1.20（1.03～1.40）、1.21（1.09～1.33）,提示T1DM组CTLA-4基因49位点G等位基因和GG、GG+AG基因型表达与对照组比较均有显著差异。结论：CTLA-4基因49位点G等位基因和GG、GG+AG基因型均与儿童T1DM的发生相关。     

CTLA-4基因多态性与过敏性紫癜的相关性研究

目的探讨CTLA-4基因多态性与儿童过敏性紫癜(HSP)的相关性。方法选取60例HSP患儿为病例组,其中男33例,女27例;另选取30例健康儿童为对照组。按有无肾脏损害将HSP患儿分为紫癜性肾炎(HSPN)组(n=30)和Non-HSPN组(n=30)。采用PCR-RFLP法,对CTLA-4基因+49及-1722位点各基因型及等位基因频率进行分析。结果 +49位点AA、AG、GG基因型及等位基因频率在病例组和对照组之间、HSPN组与Non-HSPN组之间、不同性别HSP患儿间比较差异均无统计学意义(P0.05)。-1722位点TT、TC、CC基因型及等位基因频率在病例组和对照组之间、不同性别HSP患儿间比较差异均无统计学意义(P0.05);CC基因型及T、C等位基因频率在HSPN组与Non-HSPN组间比较差异有统计学意义(P0.05)。将+49位点与-1722位点组合:各组合基因型频率在病例组和对照组之间、不同性别HSP患儿间比较差异无统计学意义(P0.05);GG+CC基因型组合在HSPN组与Non-HSPN组间比较差异有统计学意义(P0.05)。结论 CTLA-4基因+49位点A/G基因多态性与HSP发病无关;-1722位点CC基因型及C等位基因,以及+49位点GG与-1722位点CC组合基因型可能为HSPN发病的危险因素。     

Progression to type 1 diabetes and autoantibody positivity in relation to HLA-risk genotypes in children participating in the ABIS study

Background:  Autoantibodies against beta-cell antigens together with human leukocyte antigen (HLA)-risk genotypes are used as predictive markers for type 1 diabetes (T1D). In this study, we have investigated the role of HLA-risk and -protective genotypes for development of beta-cell autoantibodies and progression to T1D in healthy children.
Methods:  T1D-related HLA genotypes and autoantibodies against glutamic acid decarboxylase [glutamic acid decarboxylase antibodies (GADA)] and islet antigen-2 (IA-2A) were studied at 1, 2.5 and 5 yr of age in unselected healthy children and children with T1D participating in the All Babies In Southeast Sweden (ABIS) study.
Results:  GADA or IA-2A positivity at 5 yr of age was associated with DR4-DQ8 haplotype and DR3-DQ2/DR4-DQ8 genotype. By the age of 6–7 yr, we identified 32 children with T1D among the 17 055 participants in the ABIS study. Eight of 2329 (0.3%) non-diabetic children had permanent autoantibodies, and 143 of 2329 (6%) children had transient autoantibodies. HLA-risk genotypes associated with T1D, whereas protective genotypes were seldom found in children with T1D. Children with permanent autoantibodies had more often risk-associated DR4-DQ8 haplotype than autoantibody-negative children. No associations with HLA-risk or -protective genotypes were found for transient autoantibodies.
Conclusions:  The strong relation between HLA-risk alleles and T1D once again confirmed that HLA-risk genotypes play an important role for development of T1D. However, HLA genotypes seem not to explain induction of autoantibodies, especially transient autoantibodies, in the general population, emphasizing the role of environmental factors in the initiation of autoimmunity. It seems that HLA-risk genotypes are responsible for maturation of the permanent autoantibody response.     

Novel mutat?ons and diverse clinical phenotypes in recomb?nase-activating gene 1 deficiency

Celiac Disease (CD) occurs in patients with Type 1 Diabetes (T1D) ranging the prevalence of 4.4-11.1% versus 0.5% of the general population. The mechanism of association of these two diseases involves a shared genetic background: HLA genotype DR3-DQ2 and DR4-DQ8 are strongly associated with T1D, DR3-DQ2 with CD. The classical severe presentation of CD rarely occurs in T1D patients, but more often patients have few/mild symptoms of CD or are completely asymptomatic (silent CD). In fact diagnosis of CD is regularly performed by means of the screening in T1D patients. The effects of gluten-free diet (GFD) on the growth and T1D metabolic control in CD/T1D patient are controversial. Regarding of the GFD composition, there is a debate on the higher glycaemic index of gluten-free foods respect to gluten-containing foods; furthermore GFD could be poorer of fibers and richer of fat. The adherence to GFD by children with CD-T1D has been reported generally below 50%, lower respect to the 73% of CD patients, a lower compliance being more frequent among asymptomatic patients. The more severe problems of GFD adherence usually occur during adolescence when in GFD non compliant subjects the lowest quality of life is reported. A psychological and educational support should be provided for these patients.     

Gender-limited association of cytotoxic T-lymphocyte antigen-4 (CTLA-4) polymorphism with cord blood IgE levels

Allergic mechanism has long been attributed to IgE-mediated reaction. The relationship between gene polymorphism and cord blood IgE (CB IgE) is unclear. We investigated whether elevation of CB IgE levels was associated with polymorphisms of cytotoxic T-lymphocyte antigen 4 (CTLA-4) at (−318) CT and (+49) AG positions in a gender-limited fashion. CB IgE levels were determined by Pharmacia CAP system and the CTLA-4 polymorphisms at (−318) and (+49) were determined by restriction fragment length polymorphism (RFLP). A total of 644 consecutive umbilical cord bloods were collected for this study. 32.9% of newborn infants had detectable IgE levels (≥0.35 kU/l). 25.6% of the male newborns had elevated CB IgE levels (≥0.5 kU/l) similar to those of the female newborns (22.7%). The CTLA-4 polymorphism at (+49) but not (−318) was significantly associated with elevated CB IgE levels (p = 0.004). The association of CTLA-4 (+49) A allele with elevated CB IgE levels was found only in females. Both male and female infants with different CTLA-4 (−318) genotypes had no difference in the rates of elevated CB IgE levels. A linkage disequilibrium between CTLA-4 (+49) G and (−318) C allele was found in this Chinese population. Subjects with the (+49, GG and −318, CC) genotype had a significantly lower rate of elevated CB IgE levels. Association of the CTLA-4 (+49) polymorphism with elevated CB IgE levels was found only in female infants. Newborn infants with the (+49, GG and −318, CC) genotype tended to have a low rate of elevated CB IgE.     

Association of cytotoxic T‐lymphocyte antigen 4 +49A/G gene polymorphism with acute rejection risk in renal transplantation

The conclusions on the association between cytotoxic T‐lymphocyte antigen 4 (CTLA4) +49A/G gene polymorphism and acute rejection risk in renal transplantation are still debated. This meta‐analysis was performed to update the association between CTLA4 +49A/G and acute rejection risk in renal transplantation. The association investigations were identified from PubMed and Cochrane Library, and eligible studies were included and synthesized using meta‐analysis method. Fourteen reports were included into this meta‐analysis for the association of CTLA4 A/G gene polymorphism and acute rejection risk in renal transplantation, consisting of 962 acute rejection patients and 2084 non‐acute rejection controls. The association between CTLA4 G allele/GG genotype and acute rejection risk in renal transplantation was found in this meta‐analysis (G allele: OR=1.21, 95% CI: 1.03‐1.44, P=.02; GG genotype: OR=1.37, 95% CI: 1.10‐1.69, P=.004). However, the AA genotype was not associated with acute rejection risk in renal transplantation. In conclusion, CTLA4 G allele/GG genotype is associated with the acute rejection risk in renal transplantation.     

Pattern of human leukocyte antigens in Turkish children with celiac disease

BACKGROUND: Regional variations in the human leukocyte antigen (HLA) distribution patterns of celiac disease (CD) have been reported. The aim of the present study was to assess the distribution of HLA class I and class II in Turkish children with CD and to compare the findings with a control group. METHODS: Human leukocyte antigen typing was performed in 33 children with CD and in 77 healthy individuals, who served as controls, by using standard National Institutes of Health lymphocytotoxicity techniques. RESULTS: A positive association was found between HLA A2 (42 vs 19% for sick subjects compared with healthy controls, respectively), B8 (39 vs. 9% for sick subjects compared with healthy controls, respectively), CW7 (45 vs. 25% for sick subjects compared with healthy controls, respectively), DR3 (70 vs. 17% for sick subjects compared with healthy controls, respectively), DR7 (30 vs. 13% for sick subjects compared with healthy controls, respectively) and DQ2 (52 vs. 34% for sick subjects compared with healthy controls, respectively). The combinations of DR3-DQ2 (30 vs. 12% for sick subjects compared with healthy controls, respectively), DR3-DR4 (21 vs. 1% for sick subjects compared with healthy controls, respectively) and DR7-DQ2 (21 vs. 6% for sick subjects compared with healthy controls, respectively) were also found to be significantly important in children with CD. The highest relative risk (RR) was for HLA B8 in class I (RR 6.50), for DR3 (RR 11.30) in class II and for combination of DR3-DR4 (RR 20.46). The highest etiologic fraction (EF) was for the DR3 antigen (EF 0.55). CONCLUSIONS: The present study emphasizes that HLA genotypes are an important background to CD development, but some additional susceptibility factors remain to be identified.     

脂联素基因+45和+276多态性与川崎病的关系

目的 检测川崎病患儿脂联素基因+45T/G、+276G/T多态性分布情况,探讨其与川崎病发病和冠状动脉损伤（CAL）发生的关系。方法 采取病例对照研究方法,选取81例川崎病患儿（其中11例并发CAL）和100例正常体检儿童（对照组）。采用基因测序方法测定脂联素基因+45和+276位点的多态性分布。结果 川崎病组脂联素基因+45位点基因型TT、TG、GG以及T/G的等位基因频率与对照组比较差异无统计学意义（P > 0.05）;川崎病组中并发CAL者与无CAL者该位点的基因型分布频率和等位基因频率比较差异亦无统计学意义（P > 0.05）。川崎病组与对照组脂联素基因+276位点基因型GG、GT、TT及G/T等位基因频率的比较差异均有统计学意义（P < 0.05）;GG基因型为川崎病发病的危险因素（OR=2.313,P=0.006）。川崎病患儿中CAL组脂联素基因+276位点基因型分布与非CAL组比较差异无统计学意义（P > 0.05）。结论 脂联素基因+276位点多态性可能与川崎病的发生相关,但与CAL的发生无关;脂联素基因+45位点多态性可能与川崎病和CAL的发生均无关。     

重庆汉族儿童单核细胞趋化蛋白1基因多态性及表达水平与结核病易感性的关系

目的 分析趋化因子单核细胞趋化蛋白1(MCP-1)启动子区2518基因型频率和等位基因在重庆地区汉族儿童结核病中的分布特点,探讨MCP-1基因启动子区2518A/G多态性、血清MCP-1蛋白表达水平与结核病的相关关系.方法 研究对象为100例儿童结核病、100例成人结核病以及相应的200例健康对照.序列特异性引物PCR(PCR-SSP)技术检测MCP-1基因启动子区2518A/G多态性.ELISA方法测定相应不同基因型患者和对照血清MCP-1水平.结果 (1)总体结核病组2518位点G等位基因频率为58%,明显高于相应的健康对照组(36%)(P<0.01);(2)总体结核病组2518 GG基因型频率为65%,明显高于相应的健康对照组(27%)(P<0.01);(3)MCP-1基因启动子区2518位点GG基因型结核病患病危险性(OR=6,95%CI=3.3～11.0)高于AA基因型(OR=1.0,95%CI=0.243～1.554),且儿童GG基因型患病的危险性(OR=7,95%CI=3.0～16.6)高于成人GG基因型(OR=5.1,95%CI=2.2～12.0);(4)2518 GG基因型的MCP-1水平(124 μl/L)高于AA基因型(23.10 μg/L)和AG基因型(39.96 μg/L),三组比较差异有统计学意义(P<0.01).结核组高于正常组,儿童组高于成人组.结论 在中国重庆地区汉族人中,MCP-1-2518位GG基因型作为结核病可能的危险因素,在儿童结核病的发病中具有较成人更重要的意义.     

Genetic polymorphisms of CD14, toll-like receptor 4, and caspase-recruitment domain 15 are not associated with necrotizing enterocolitis in very low birth weight infants

OBJECTIVES: Inadequate response of the innate immune system to bacterial antigens present in the intestinal flora may play a role in the development of necrotizing enterocolitis (NEC). Pattern recognition receptors such as CD14, toll-like receptor (TLR) 4, and caspase-recruitment domain (CARD) 15 bind bacterial lipopolysaccharide and peptidoglycan, and their activation leads to production of inflammatory cytokines. Our aim was to evaluate whether single nucleotide polymorphisms (SNPs) of CD14, TLR4, and CARD15 are associated with the risk of NEC in very low birth weight (VLBW) infants. PATIENTS AND METHODS: We determined the CD14 C-260T, TLR4 A +896G, C +1196T, and CARD15 G +2722C, C +2104T, 3020insC functional SNPs in dried blood samples from 118 VLBW infants (of those, 41 developed NEC) and from 146 healthy term newborns using polymerase chain reaction and restriction fragment length polymorphism methods. We tested the association between genotype and risk of NEC. RESULTS: No significant differences were found in the prevalence of CD14 -260T, TLR4 +896G, +1196T, and CARD15 +2722C, +2104T, 3020insC alleles between VLBW infants and healthy term newborns (P = NS). The frequencies of investigated genotypes were similar in infants with and without NEC (P = NS). Furthermore, we did not find any association between genotype and prematurity or sepsis, which are important risk factors of NEC. CONCLUSIONS: Carrier state of the tested CD14, TLR4, and CARD15 SNPs is not associated with NEC risk in VLBW infants.     

IL-6 C-572G多态性位点与自发性早产遗传易感性的关系

目的探讨IL-6基因C-572G多态性位点与自发性早产(SPTB)遗传易感性的关联性。方法研究对象来自北京及其周边地区。病例组包括569例SPTB新生儿,其中超早产儿(胎龄28周)56例、极早产儿(胎龄28~31~(+6)周)166例和中晚期早产儿(胎龄32~36~(+6)周)347例。对照组包括673例足月新生儿。采用最新的Sequenom Mass ARRAY~?SNP检测技术对IL-6基因C-572G位点进行单核苷酸多态性分型。结果与携带IL-6基因C-572G位点的CC基因型的个体相比,携带至少1个G等位基因型(CG+GG基因型)的个体发生中晚期SPTB的风险显著升高(OR=1.35,95%CI:1.01~1.80,P=0.04)。结论在该中国人群中,IL-6基因C-572G多态性位点与中晚期SPTB患病风险的增加存在显著的遗传学关联。     

CTLA-4启动子-318C/T基因多态性与哮喘患儿血清总IgE水平的关系

目的探讨细胞毒T淋巴细胞相关抗原4(CTLA-4)启动子-318(C/T)基因多态性和吉林长春地区哮喘患儿血清总IgE水平的关系,以便为哮喘的诊治提供新线索。方法随机选取90例哮喘患儿及100例健康体检儿童作对照组,哮喘组和对照组的性别和年龄差异无统计学意义。采用聚合酶链式反应—限制性片段长度多态性(PCR-RFLP)技术对哮喘组和对照组CTLA-4启动子-318(C/T)基因多态性进行检测分析;同时采用酶联免疫吸附试验(ELISA)检测不同基因型哮喘患儿血清总IgE水平。结果CTLA-4启动子-318位点存在基因多态性。血清总IgE水平哮喘组(M=308.92 IU/ml,Q=254.75)高于正常对照组(M=36.66 IU/ml,Q=33.57),P<0.01;哮喘组中基因型为野生型(CC型,M=375.86 IU/ml,Q=139.95),高于突变型(TT型 CT型,M=141.25 IU/ml,Q=47.73),P<0.01。结论CTLA-4启动子-318(C/T)存在基因多态性,该位点的基因多态性可能引起血清总IgE水平下调。     

Interferon-gamma Low producer genotype +874 overrepresented in Bacillus Calmette-Guerin nonresponding children

BACKGROUND: There are limited reports on the influence of the immune regulatory genotypes on the efficacy of Bacillus Calmette-Guerin (BCG) in man. This study was designed to evaluate the influence of the cytokine genotype interferon (IFN)-gamma +874T/A on T cell in vitro assays in BCG nonresponders (negative to either in vivo or in vitro test with purified protein derivative or both). METHODS: Ninety healthy children who were without any clinical evidence of the disease, 45 with a BCG-scar and the remaining 45 without scar were assessed for in vitro T cell responses. CD4+ and CD8+ cell counts were measured by flow cytometry. r32kDaBCG (Ag85A-BCG) protein was used to stimulate T cells and IFN-gamma cytokine concentration in the cultures were measured by enzyme-linked immunosorbent assay. Polymorphism in IFN-gamma (+874T/A) region was detected by amplification refractory mutation system-polymerase chain reaction. RESULTS: T cell subsets were within the normal range in all subjects. Children with TT genotype showed significantly higher antigen-induced IFN-gamma (P < 0.001) as compared with those with AT/AA genotype. The highest values were observed in children with TT genotype combined with positive antigen-specific peripheral blood mononuclear cells proliferation. Seventy-five percent of the vaccinated children with TT genotype showed high amounts of stimulated IFN-gamma compared with 66% of scar negative and 16% of scar positive but with AA genotype. CONCLUSIONS: IFN-gamma (+874T/A) polymorphism seemed to be a strong and independent predictor for clinical outcome of both scar-positive and scar-negative children. These results may help in planning future vaccination strategies. The ability to mount in vitro lymphoproliferation did not distinguish the success or failure of BCG vaccination nor predict susceptibility to the disease.     

IL-13 基因+2044G/A 多态性与儿童哮喘风险和血清IL-13 水平的相关性研究

目的探讨IL-13基因+2044G/A多态性与儿童哮喘发病风险及哮喘儿童血清IL-13水平的关系。方法采用PCR-RFLP和ELISA方法,对90例支气管哮喘患儿(哮喘组)和82例健康儿童(对照组)IL-13基因+2044G/A多态性和血清IL-13水平进行检测,计算基因型、等位基因频率及其所对应的血清IL-13水平。结果哮喘组和对照组IL-13+2044G/A多态性3种基因型的分布差异有统计学意义(P0.001);与GG基因型比较,GA基因型儿童哮喘风险增加3.52倍(95%CI:1.82~6.82),AA基因哮喘风险增加3.71倍(95%CI:1.06~12.97)。哮喘组A等位基因频率为36.1%,高于对照组的18.3%,差异有统计学意义(P0.001)。与G等位基因比较,A等位基因携带儿童哮喘风险增加2.53倍(95%CI:1.53~4.16)。哮喘组患儿血清IL-13水平为151.82(134.33~166.68)ng/L,对照组为79.00(58.74~111.09)ng/L,两组差异有统计学意义(P0.001)。哮喘组GG、GA和AA基因型的血清IL-13水平均分别高于对照组,差异有统计学意义(P均0.01)。哮喘组GG、GA和AA 3种基因型之间血清IL-13水平的差异也有统计学意义(P0.01),其中GA和AA基因型血清IL-13水平高于GG基因型。结论 IL-13基因+2044G/A多态性与支气管哮喘儿童血清IL-13水平具有关联性,且A等位基因可能造成了哮喘儿童血清高IL-13水平,携带A等位基因的儿童哮喘风险增加。     

胞浆型磷脂酶A2多态性与儿童支气管哮喘发生及孟鲁司特疗效的相关性

目的 探究胞浆型磷脂酶A2（PLA2G4）基因rs932476位点多态性与儿童支气管哮喘发生及白三烯受体拮抗剂孟鲁司特治疗反应性的相关性。方法 收集支气管哮喘患儿128例为病例组,100例健康儿童为对照组。比较两组儿童PLA2G4基因rs932476位点基因型及等位基因分布。病例组患儿采用常规治疗+孟鲁司特方案治疗2个月。比较病例组患儿治疗前后血清白三烯B4（LTB4）及炎性因子白细胞介素-4（IL-4）、免疫球蛋白E（IgE）和γ-干扰素（IFN-γ）、肺功能和呼出气一氧化氮（FeNO）的水平。结果 PLA2G4基因rs932476位点基因型及等位基因频率在病例组和对照组之间及不同严重程度哮喘组之间的分布差异均无统计学意义（P > 0.05）。治疗后AA型患儿总有效率高于GG型,差异有统计学意义。与治疗前相比,治疗后各基因型患儿血清IgE和IL-4水平降低,IFN-γ水平升高（P < 0.05）。治疗后GG型患儿血清IL-4水平高于AA型,IFN-γ的水平低于AA型。治疗后,各基因型患儿的肺功能参数升高,其中AA型患儿显著高于GG型;而FeNO水平治疗后明显下降,其中AA型患儿明显低于GG型。病例组治疗前血清LTB4水平明显高于对照组（P < 0.05）。治疗后病例组血清LTB4水平明显降低（P < 0.05）,其中GG基因型患儿LTB4水平高于AA型（P < 0.05）。结论 PLA2G4基因rs932476位点多态性与儿童支气管哮喘的易感性及病情严重程度无关,但对白三烯受体拮抗剂孟鲁司特的疗效有一定的影响,其机制可能与影响LTB4水平有关。     

原发性肾病综合征与细胞毒性T淋巴细胞相关抗原-4基因启动子区-318位点基因多态性的相关性

目的探讨细胞毒性T淋巴细胞相关抗原-4(CTLA-4)与糖皮质激素(GC)耐药型原发性肾病综合征(PNS)中系膜增生性肾小球肾炎(MsPGN)的相关性。方法应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测36例PNS-MsPGN患儿和30例正常对照儿童CTLA-4基因启动子区-318位点基因型。结果肾病组CTLA-4基因启动子区-318位点基因型频率分别为CC型38.9%、TC型61.1%和TT型0,等位基因频率为C等位基因69.4%、T等位基因30.6%。肾病组各基因型及等位基因频率与对照组相比均无显著差异(P均>0.03)。结论CTLA-4基因启动子区-318位点基因C/T双态性同GC耐药型PNS-MsPGN患儿无相关性,提示该基点基因多态性可能不参与GC耐药型PNS-MsPGN的发病机制及耐药机制。     

An exploration of Glo‐3A antibody levels in children at increased risk for type 1 diabetes mellitus

Aims: To determine whether Glo‐3A, (formerly referred to as homologue of Glb1 or Glb1) antibodies are associated with islet autoimmunity (IA) in children at increased risk for type 1 diabetes (T1D) and to investigate their relation with environmental correlates of T1D. Methods: We selected a sample from the Diabetes Autoimmunity Study in the Young (DAISY), a prospective study of children at increased risk for T1D. Cases were positive for insulin, glutamic acid decarboxylase (GAD), or insulinoma‐associated antigen‐2 (IA‐2) autoantibodies on two consecutive visits and either diagnosed with diabetes mellitus or still autoantibody positive when selected. Controls were from the same increased risk group, of similar age as the cases but negative for autoantibodies. Sera from 91 IA cases and 82 controls were analyzed in a blinded manner for immunoglobulin G (IgG) antibodies to Glo‐3A by ELISA. Results: Adjusting for family history of T1D and human leukocyte antigen (HLA)‐DR4 positivity, Glo‐3A antibodies were not associated with IA case status (OR: 1.01, 95% CI: 0.99–1.03). Adjusting for age, family history of T1D, and HLA‐DR4 positivity, Glo‐3A antibody levels were inversely associated with breast‐feeding duration (beta = ?0.08, p = 0.001) and directly associated with current intake of foods containing gluten (beta = 0.24, p = 0.007) in IA cases but not in controls. Zonulin, a biomarker of gut permeability, was directly associated with Glo‐3A antibody levels in cases (beta = 0.73, p = 0.003) but not in controls. Conclusion: Differing correlates of Glo‐3A antibodies in IA cases and controls suggest an underlying difference in mucosal immune response.     

Analysis of cytotoxic T lymphocyte antigen-4 (CTLA-4) exon 1 polymorphism in patients with type 1 diabetes mellitus in a Turkish population

Recent studies have described linkage and association between cytotoxic T-lymphocyte antigen-4 (CTLA-4) gene polymorphism and type 1 diabetes mellitus (DM1) in some ethnic populations, but not others. This finding suggests that CTLA-4 gene association with DM1 may be influenced by the racial composition of the population. Thus, it is important to study the polymorphism of the CTLA-4 gene in different ethnic groups. In this case-control association study, the CTLA-4 gene exon 1 A/G polymorphism was analyzed in 48 children with DM1 and 80 healthy controls using polymerase chain reaction-restriction fragment length polymorphism analysis. The possible interaction of the CTLA-4 gene polymorphism with the presence of established genetic markers (HLA-DR genotyping) was also evaluated in 29 patients. The results of the present study do not suggest an association of the known polymorphism in exon 1 of the CTLA-4 gene with DM1 in this Turkish population, and G-allele containing CTLA-4 genotypes were not preferentially associated with age at clinical presentation or with presence of other genetic (HLA-DR3 or -DR4) markers of DM1.     

脂联素基因SNP276多态性与儿童青少年肥胖的相关性研究

目的研究脂联素（APM1）基因SNP276 G/T多态性与儿童青少年单纯性肥胖及其代谢指标的相关性。方法以2004至2006年于复旦大学附属儿科医院内分泌门诊就诊的单纯性肥胖或超重儿童青少年分别作为肥胖组和超重组;选择某中学正常体重学生作为正常对照组。分别测量身高和体重,计算体重指数（BMI）。测定血清空腹葡萄糖（FPG）、空腹胰岛素(FIns)、三酰甘油(TG)和总胆固醇(TC)水平。计算胰岛素抵抗指数（HOMA-IR）和胰岛素敏感指数（QUICKI）。抽提外周血基因组DNA,采用Taqman-MGB探针技术检测APM1基因SNP276 G/T多态性,分析不同基因型与代谢指标和BMI间的关联性。 结果肥胖组纳入227例,超重组纳入231例,正常对照组纳入216名。①肥胖+超重组的BMI、FPG、FIns、TG和HOMA-IR均显著高于正常对照组。②基因分布频率符合Hardy-Weinberg平衡。③肥胖组、超重组和正常对照组的G等位基因频率分别为71.4％、72.5％和69.7％,GG基因型频率分别为50.2％、52.4％和45.8％,GT基因型频率分别为42.3％、40.3％和47.7％;各组差异均无统计学意义（P均>0.05）。 ④SNP276 GG、GT和TT基因型的BMI、FPG、FIns、TG、TC、HOMA-IR和QUICKI差异均无统计学意义（P＝0.49~0.99）。⑤肥胖+超重组IFG儿童青少年中GG+GT型有70例,TT型4例;正常对照组IFG儿童青少年中GG+GT型有10例,TT型0例;两组差异无统计学意义（P＝0.45）。结论APM1基因SNP276 G/T多态性与青少年儿童单纯性肥胖及其代谢指标间无显著关联性,提示该SNP位点可能存在种族特异性。     

Association of the PTPN22/LYP gene with type 1 diabetes

OBJECTIVES: The goal of this study was to verify the association between type 1 diabetes (T1D) and the protein tyrosine phosphatase, non-receptor type 22 (PTPN22) gene in non-Hispanic whites (NHWs) and Hispanics from Colorado. SUBJECTS AND METHODS: The C1858T single-nucleotide polymorphism within the PTPN22 gene was genotyped in 753 patients with T1D ascertained from the diabetes clinic at the Barbara Davis Center in Denver and 662 control population. RESULTS: Both the PTPN22 CT genotype [odds ratio (OR) = 1.96; p < 0.0001] and TT genotype (OR = 4.41; p = 0.02) were significantly associated with T1D in the NHW population. While the association was stronger in subjects with non-HLA-DR3/4 genotypes than in those with the HLA-DR3/4 genotype, regression analyses did not reveal significant interaction between PTPN22 genotypes and HLA-DR3/4. The strength of the association was similar in males and females, patients diagnosed before and after age 10 yr, and in Hispanics and NHWs. CONCLUSION: In this study, we confirm that PTPN22 is associated with T1D in the Colorado population.