TCF7L2基因rs7903146的多态性与2型糖尿病肥胖的相关性

【目的】探讨TCF7L2基因rs7903146的多态性与2型糖尿病（T2DM ）肥胖的相关性。【方法】收集T2DM 患者216例（DM组）,根据体质量指数（BMI）又分为肥胖T2DM组（BMI＞25 kg／m2）和正常T2DM组（BMI≤25 kg／m2）,另外收集健康体检者194例,根据体质量指数（BMI）又分为肥胖对照组（BMI＞25 kg／m2）和正常对照组（BMI≤25 kg／m2）,采用 PCR‐RFLP技术检测各组 TCF7L2基因 rs7903146多态性并比较。【结果】T2DM组与对照组TCF7L2基因rs7903146位点基因型及等位基因频率分布比较差异无统计学意义（ P ＞0．05）;肥胖DM组与正常DM组、肥胖对照组与正常对照组 TCF7L2基因rs7903146位点基因型分布、等位基因频率比较均有统计学意义（ P ＜0．05）,肥胖DM 组与肥胖对照组、正常DM 组与正常对照组基因型分布、等位基因频率比较均无统计学意义（ P ＞0．05）。【结论】TCF7L2基因rs7903146位点变异不是糖尿病发病的危险因素,有可能是引起肥胖的重要遗传因素。     

辽宁地区FoxO3a基因rs4946936多态性与2型糖尿病的相关性研究

【目的】探讨FoxO3a基因rs4946936单核苷酸多态性与辽宁地区2型糖尿病（T2DM）相关性。【方法】收集374例T2DM患者（T2DM组）及283例非糖尿病健康人群（对照组）,检测两组FoxO3a基因rs4946936单核苷酸多态性,比较两组等位基因与基因型分布频率。【结果】T2DM组中C等位基因、CC基因型频率分别为76．74％、58．82％,与对照组的C等位基因频率77．21％、CC基因型58．66％比较差异无统计学意义（P〉0．05）。【结论】FoxO3a基因rs4946936单核苷酸多态性与T2DM无相关性。     

IFN-γ基因+874位点单核苷酸多态性与乙型肝炎病毒感染关系的研究

【目的】研究干扰素（IFN-γ）基因＋874位点单核苷酸多态性与乙型肝炎病毒（HBV）感染、转归的关系,探讨HBV感染的遗传易感因素。【方法】采用序列特异性引物-聚合酶链反应（PCR—SSP）技术检测231例慢性HBV感染者、165例自限性HBV感染者和135名正常对照者IFN-γ基因第一内含子＋874位点T／A单核苷酸多态性。【结果】慢性HBV感染组IFN-γ基因＋874位点AA基因型频率（78．8％）显著高于正常对照组（64．4％）（x^2=9．60．P=0．008）,而自限性HBV感染组（62．4％）和对照组之间差异无显著性（x^2=0．16,P=0．92）。进一步比较慢性HBV感染者IFN-γ基因＋874住点单核苷酸多态性与HBV—DNA复制的关系,发现IFN-γ基因＋874住点基因型和等住基因频率在低水平HBV-DNA组和高水平HBV-DNA组之间的分布差异无显著性。【结论】IFN-γ基因第一内含子＋874位点多态性与慢性HBV感染有关,提示该位点多态性可能在决定个体HBV感染遗传易感性方面有一定意义。     

PC-1基因外显子4多态性与中国人2型糖尿病相关性的系统评价

目的系统评价浆细胞膜糖蛋白l（plasmacellglycoprotrin-1,PC-1）基因第4外显子K121Q多态性与中国人2型糖尿病（type2diabetesmellitus,T2DM）的相关性。方法计算机检索CNKI、VIP、CBM、PubMed、EMbase、qheCochraneLibrary（2012年第3期）和WanFangData,查找国内外关于PC．1基因第4外显子K121Q多态性与T2DM相关性的病例-对照研究,检索时限均从1980年至2012年。由2位评价者根据纳入与排除标准独立筛选文献、提取资料并评价质量后,采用RevMan5．0和Stata12．0软件进行Meta分析,采用Egger’S线性回归法分析发表偏倚。结果最终纳入11个研究,包括T2DM患者1637例,对照1730例。Meta分析结果显示：对于中国人群,基因型K／Q人群的T2DM发病风险高于基因型K／K人群[OR=I．84,95％CI（1．19,2．85）,P=0．006];基因型Q／Q＋K／Q人群的T2DM发病风险高于基因型K／K人群[OR=I．92,95％CI（1．18,3．14）,P=0．009];等位基因Q人群的T2DM发病风险高于等位基因K人群[OR=I．83,95％CI（1．16,2．89）,P=0．01010结论中国人群PC-1基因第4外显子K121Q等位基因Q与T2DM发病有关。受纳入研究数量及质量所限,上述结论尚待进一步研究加以验证。     

维生素D受体基因多态性与2型糖尿病的易感性研究

【目的】探讨维生素D受体基因BsmI、ApaI位点多态性与汉族人群2型糖尿病的相关性。【方法】采用PCR-限制性多态性片断长度（RFLP）技术检测83例健康对照（NC）者、96例2型糖尿病（T2DM）患者的维生素D受体BsmI、ApaI位点基因型和等位基因频率。【结果】①T2DM组与NC组BsmI位点基因型、等位基因频率分布差异有统计学意义（均P〈0．05）,两组间等位基因B的相对风险率为2．50。②T2DM组与Nc组Apal位点基因型、等位基因频率分布差异均无统计学意义（x2=0．344,P=0．842;x2=0．090,P=0．765）。【结论】维生素D受体基因BsmI位点与2型糖尿病的发生密切相关,等位基因B可能是2型糖尿病的易感基因。     

辽宁地区汉族 IL-1βrs16944基因多态性与2型糖尿病的相关性研究

【目的】探讨白介素-1β（IL-1β） rs16944基因多态性与2型糖尿病（T2DM ）的关系。【方法】利用提取基因组DNA及Mass ARRAY 分子量阵列技术对健康对照组人群366人及T2DM患者583例进行基因多态性分析。【结果】IL-1βrs16944基因 AA、AG、GG三种基因型在健康对照组中分布频率分别为22．40％、50．00％、27．60％,在T2DM组中分布频率分别为20．58％、50．09％、29．33％,等位基因 A在健康对照组及T2DM组中分布频率分别为47．40％及45．63％,等位基因G在两组中分布频率分别为52．60％及54．37％,两组各基因型及等位基因型分布相比较无显著性差异（ P ＞0．05）。【结论】IL-1β rs16944基因其多态性可能与辽宁地区T2DM 无关。     

中国汉族健康人群多巴胺D1受体-48A／G基因多态性与精神分裂症的相关性

目的：探讨中国汉族健康人群多巴胺D1受体-48A／G基因多态性与高加索、德国及日本健康人群和精神分裂症患者的差异。方法：收集2004-03／07在武汉大学人民医院精神卫生中心和武汉市第二精神病医院住院治疗的精神分裂症患者117例（精神分裂症组）及同期体检的中国健康汉族人188例（对照组），均来自湖北省，无血缘关系。分析-48A／G基因型在不同种族间（中国汉族与高加索、德国及日本人群）、精神分裂症患者和正常人群、不同家族史精神分裂症患者和正常人群的分布差异，采用聚合酶链反应-限制性片段长度多态性法。结果：有117例精神分裂症患者和188例正常人的样本纳入结果分析。①不同种族间多巴胺D1受体-48A／G基因型分布的比较：中国汉族健康人群-48A／G等位基因的分布高于高加索和德国人群，低于日本人群（X^2=65．728，18．281，9．929；P均〈0．01）；在基因型的分布上，与日本人群差异也存在显著性（X^2=8．191，P〈0．01）。②精神分裂症组和对照组多巴胺D1受体-48A／G基因多态性分布的比较：两组基因型分布及等位基因均差异无显著性（X^2=-1．179，0．072，P均〉0．05）。③不同家族史精神分裂症组和对照组多巴胺D1受体-48A／G基因多态性分布的比较：有精神分裂症家族史患者AA基因型频率高于对照组（91．7％和71.3％，，X^2=6．621，P〈0．01），A等位基因频率明显高于对照组（69／72和320／376，X^2=6．081，P〈0．05）。结论：中国汉族健康人群与文献报道的高加索、德国及日本人群多巴胺D1受体-48A／G等位基因分布存在显著性差异，在基因型的分布上，与日本人群也存在显著性差异；精神分裂症患者和正常人群的基因型频率和等位基因频率的分布相似；有精神分裂症家族史患者AA基因型频率及A等位基因频率明显高于正常人群，提示中国汉族人群中多巴胺D1受体-48A／G基因多态性可能与精神分裂症发病有关，A等位基因可能是精神分裂症发病的风险因子之一。     

TGFβ1—800G〉A基因多态性与自发性脑出血的相关性研究

【目的】探讨转化生长因子β1（TGF-β1）基因多态性与自发性脑出血（CH）的关系。【方法】检测202例CH患者及167例性别、年龄匹配的健康体检者一800G〉A多态位点的基因型,并计算出各等位基因频率在两组中的频率分布。【结果】中国湖南汉族人群中存在-800G〉A位点多态性,-800G〉A基因型在两组人群中的分布符合Hardy-Weinberg平衡,脑出血组与对照组相比,基因型及等位基因频率分布差异无显著性（P〉0．05）,logistic回归分析未发现某种基因型增加或者降低脑出血发生的风险。【结论】TGF-β1-800G〉A基因多态性与中国湖南地区汉族人群自发性脑出血无明显相关性。     

E-选择素基因多态性与新疆维吾尔族、汉族原发性高血压相关性研究

【目的】探讨E一选择素基因rs5361A／C、rs5355C／T两个等位基因多态性与新疆维吾尔族、汉族原发性高血压之间的相关性。【方法】选择新疆维吾尔族、汉族原发性高血压患者309例和368例,同时选取维吾尔族、汉族正常对照组300例和349例,采用TaqMan探针法对E选择素基因的2个等位基因多态性rs5361A／C、rs5355c／T进行检测。【结果】新疆维吾尔族、汉族原发性高血压组与正常对照组中rs5361A／C基因多态性均存在显著差异（P〈0．01）,而新疆维吾尔族、汉族原发性高血压组与正常对照组中rs5355C／T基因多态性均无显著差异（P〉0．05）。【结论]E一选择素基因rs5355C／T等位基因多态性与新疆维吾尔族、汉族原发性高血压均无显著相关性,E一选择素基因rs5361C／T等位基因多态性与新疆维吾尔族、汉族原发性高血压均显著相关,E一选择素基因rs5361等位基因CC型可能是新疆维吾尔族和汉族原发性高血压病的独立致病因素。     

核苷酸内焦磷酸酶磷酸二酯酶1 基因 K121Q 多态性与2 型糖尿病的相关性研究

目的探讨中国黑龙江汉族人群核苷酸内焦磷酸酶磷酸二酯酶1（Ecto—nucleotidepyrophosphatase／phosphodies-terase1,ENPPl）基因第4外显子K121Q对糖尿病发病的影响及其两者之间的关系。方法运用聚合酶链反应一限制性片段长度多态性（PCR—RFLP）方法检测146例2型糖尿病（T2DM）患者（T2DM组）和238例糖耐量正常对照健康人（对照组）EN—PPl基因K121Q的多态性分布,同时检测其临床及生化指标,进行随机对照研究。结果①T2DM组XQ（KQ＋QQ）基因型频率高于对照组（21．23％VS10．50％,P=0．0038）,其Q等位基因频率亦高于对照组（10．96％VS5．25％,P=0．0034）,差异有统计学意义;②携带Q等位基因个体与携带K等位基因个体两组比较,在性别构成、年龄、身高、体重、体重指数（BMI）l、腰围、臀围、腰臀比（WHR）、收缩压（SBP）、舒张压（DBP）、空腹血糖（FPG）、空腹胰岛素水平（FINS）、HOMA—IR差异均无统计学意义（P〉0．05）;（④Logistic回归显示,ENPPl基因K121Q多态性与T2DM相关（OR=2．30,95％CI=1．29—4．08,P=0．0038）;④汉族人群Q等位基因携带频率低于其他人群（非西班牙裔白人、美国黑人和西班牙人）。结论①ENPPl基因K121Q位点Q等位基因与中国黑龙江省汉族人群T2DM发病相关;②T2DM患者中携带Q等位基因个体无明显胰岛素抵抗表现;（~）ENPPl基因K121Q位点的多态性有明显种族地域差异性。     

Association of CTLA-4 gene A/G polymorphism in Japanese type 1 diabetic patients with younger age of onset and autoimmune thyroid disease

OBJECTIVE: We studied the association between type 1 diabetes with autoimmune thyroid disease (AITD) and A/G allele polymorphism in exon 1 of the CTLA-4 gene in a Japanese population. RESEARCH DESIGN AND METHODS: We studied 74 Japanese type 1 diabetic patients with or without AITD and 107 normal subjects to identify the association between CTLA-4 polymorphism and type 1 diabetes using polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS: The frequency of the CTLA-4 G allele differed significantly between the type 1 diabetic patients (61%) and the normal control subjects (48%) (P = 0.016). The difference in the CTLA-4 G allele became greater between patients with a younger age of onset of type 1 diabetes (age at onset <30 years) and the normal control subjects (64% and 48%, respectively). However, the frequency of the CTLA-4 G allele did not differ between type 1 diabetic patients with younger and older age of onset (64% vs. 57%). The G allele frequencies in the patients with younger-onset type 1 diabetes and AITD increased more than in the control patients (P = 0.025). These differences reflected a significant increase in the frequency of G/G genotype--that is, 54% in those with younger-onset type 1 diabetes and AITD, 39% in those without AITD, and 28% in control subjects. CONCLUSIONS: An association was detected between the CTLA-4 gene polymorphism and younger-onset type 1 diabetes with AITD. The G variant was suggested to be genetically linked to AITD-associated type 1 diabetes of younger onset in this apanese population. The defect in these patients presumably lies in a T-cell-mediated autoimmune mechanism.     

Association between epidermal growth factor +61 G/A polymorphism and glioma risk in a Chinese Han population

The association between the +61 G/A polymorphism of the epidermal growth factor (EGF) gene and glioma risk remains controversial and unclear. The objective of this study was to investigate the association between the EGF +61 G/A polymorphism and glioma risk in a Chinese Han population. Peripheral blood samples were extracted from 160 glioma patients and 320 control subjects. Genotyping was performed using a polymerase chain reaction-restriction fragment length polymorphism method. Glioma patients had a significantly higher frequency of the AA genotype (odds ratio [OR] 1.93, 95% confidence intervals [CI] 1.08, 3.44) than control subjects and the frequency of the AA genotype was significantly higher in glioblastoma patients than in patients with other gliomas (OR 2.19, 95% CI 1.05, 4.57). Patients with grade IV gliomas had a significantly higher frequency of the AA genotype (OR 2.25, 95% CI 1.08, 4.71) than patients with lower grade gliomas. This study demonstrated that the EGF +61 AA genotype is associated with an increased risk of glioma in a Chinese Han population.     

Association of the CTLA-4 gene 49 A/G polymorphism with type 1 diabetes and autoimmune thyroid disease in Japanese children

OBJECTIVE: To clarify the role of the T-lymphocyte-associated-4 (CTLA-4) polymorphism in the susceptibility to child-onset type 1 diabetes with regard to its clinical characteristics and complications with autoimmune thyroid disease (AITD) in the Japanese population. RESEARCH DESIGN AND METHODS: The CTLA-4 49 A/G polymorphism was detected by the PCR-restriction fragment-length polymorphism (RFLP) method in 97 type 1 diabetic subjects and 20 patients with Graves' disease, a cohort which included 4 patients who also had type 1 diabetes. RESULTS: The genotypes and allele frequencies of this polymorphism did not differ between the type 1 diabetic subjects and the control subjects. The G allele frequency was 63.9% in the type 1 diabetic subjects. The G allele frequency in the subgroup of patients with a high titer of autoantibodies to the GAD antibody (Ab) was 72.9% (P = 0.0499 vs. control subjects); in the subgroup of patients without HLA DRB1*0405, it was 72.6% (P = 0.0271 vs. control subjects); and in the subgroup of patients with a residual beta-cell function, it was 78.6% (P = 0.0391 vs. control subjects). The G allele frequency in the patients with Graves' disease was also significantly higher at 78.1% (P = 0.0405 vs. control subjects). Furthermore, the frequency in our diabetic subjects complicated with Graves' disease was even higher (87.5%). CONCLUSIONS: We have demonstrated that a distinct association exists between the G allele of CTLA-4 and high values of GAD Ab, residual beta-cell function, and the absence of HLA-DRB1*0405.     

PC-1基因K121Q变异与2型糖尿病的关系

目的探讨浆细胞膜糖蛋白(PC1)基因4号外显子K121Q多态性与2型糖尿病及临床特征的相关性。方法用聚合酶链反应限制性内切酶片段长度多态性分析(PCR RFLP)、DNA测序等技术检测上海地区汉族人群中165例2型糖尿病患者和98名正常糖耐量对照者PC1基因K121Q的多态性分布情况,同时采用PCR单链构像多态性分析(PCR SSCP)筛查该区域其他可能与2型糖尿病发生有关的多态性位点。结果糖尿病患者中KK基因型143例(86.67%),KQ基因型22例(13.33%),QQ基因型0例(0.00%),K、Q等位基因频率分别为93.33%和6.67%;正常对照组中KK基因型85例(86.73%),KQ基因型12例(12.25%),QQ基因型1例(1.02%),K、Q等位基因频率分别为92.86%和7.14%,2组人群的基因型和等位基因频率差异无显著性(P>0.05);2型糖尿病患者中Q等位基因携带者的胰岛素抵抗指数(IR)、血糖、胰岛素、血脂等均略高于KK基因型的患者,但两者之间的差异均无显著性;中国上海地区汉族人群Q等位基因频率明显低于欧洲白种人。结论目前尚不能确定PC1基因K121Q多态性与上海地区汉族人群胰岛素抵抗及2型糖尿病发病相关;PC1基因的K121Q多态性具有明显的种族差异。     

辽宁地区FoxO1基因rs17446593多态性与2型糖尿病的关系

【目的】探讨FoxO1基因rs17446593单核苷酸多态性与2型糖尿病（T2DM ）的关系。【方法】395例T2DM患者和366例对照组,用分子量阵列技术（MassARRAY）方法检测FoxO1基因 rs17446593单核苷酸多态性,并用SPSS13．0统计软件进行分析。【结果】FOXO1基因 rs17446593在 T2DM 组GG、GA 型及AA型分别为1．77％、27．09％及71．14％,在对照组GG、GA型及AA型分别为1．64％、20．22％及78．14％（两组间χ2＝5．0460,P ＝0．080）。G等位基因在两组分别为15．32％,及11．75％（两组间χ2＝4．116,P ＝0．042）。【结论】FoxO1基因 rs17446593 G等位基因可能是T2DM的易感基因。     

Type 1 diabetes is insulin -2221 MspI and CTLA-4 +49 A/G polymorphism dependent

BACKGROUND: Several studies have demonstrated an association of type 1 diabetes with specific alleles of HLA class II molecules, as with polymorphisms of insulin gene region. The aim of our study was to evaluate the interaction of insulin -2221 MspI polymorphism to type 1 diabetes susceptibility in connection with autoimmunity associated gene--CTLA-4 polymorphism. MATERIALS AND METHODS: Insulin -2221 MspI C/T and CTLA-4 +49 A/G polymorphisms were detected by restriction fragment-length polymorphism analysis or oligonucleotide hybridization in type 1 (n = 69), type 2 diabetes (n = 301) patients and 158 healthy controls. Regression model adjusted for age, gender and gene polymorphisms was studied. RESULTS: C-allele of insulin -2221 MspI and G-allele of +49 CTLA-4 were significant risk factors for type 1 diabetes (crude OR 3.53 and 1.59, respectively) and this impact increased in the homozygous form of both alleles. The regression model supported the idea of insulin CC and CTLA-4 GG genotypes for an independent and clearly significant risk for developing type 1 diabetes. We could not detect any significant correlation between investigated polymorphisms and type 2 diabetes. CONCLUSIONS: There exists a significant association between the C-allele of -2221 MspI in the insulin gene and type 1 diabetes. The CTLA-4 G-allele is also positively correlated with type 1 diabetes. According to the regression model the investigated gene polymorphisms are independent risk factors for development of type 1 diabetes in the Estonian population. We propose that -2221 MspI is a good marker for evaluation of risk of insulin gene haplotype in type 1 diabetes patients.     

抵抗素基因外显子及部分内含子单核苷酸多态性与2型糖尿病的关联研究

目的 探讨抵抗素基因四个外显子和部分内合子是否存在单核苷酸多态性，及其与2型糖尿病的相关性。方法 选取中国安徽地区汉族人2型糖尿病患者307例。正常对照102例。采用聚合酶链反应-单链构象多态方法，对抵抗素基因的四个外显子及部分内含子进行筛查，并做进一步基因分析。结果 在安徽地区汉族人中存在抵抗素基因的单核苷酸多态性，分别为-157G／A、＋115C／G、＋877G／C；2型糖尿病组与对照组基因型及等位基因频率差异均无显著性（均为P〉0．05）。结论 在安徽地区汉族人中，抵抗素基因存在单核苷酸多态性，但与2型糖尿病无相关性。     

CYP1A2*1F基因多态性与肺癌术后化疗疗效及预后的关系

[目的] 探讨细胞色素P4501A2(CYP1A2)*1F基因多态性与肺癌术后化疗疗效及预后的关系.[方法]对100例肺癌患者进行CYP1A2基因多态性检查,分析CYP1A2*1F与肺癌术后化疗效果及预后的相关性.[结果] ①100例患者,部分缓解 24例,稳定 44例,临床获益率为68.00%,患者CYP1A2*1F基因型以A/A型(49.00%)为主,其次为A/C型(38.00%);②临床获益患者中A/A基因型所占比例略高于未获益患者,但差异无显著性(P>0.05);③携带CYP1A2*1F A/A基因型患者总生存时间略高于A/C型、C/C型,但各组之间相比较差异无显著性(P>0.05).[结论] CYP1A2*1F突变基因型与肺癌术后化疗效果及预后无明显相关性.     

TNF-α及CTLA-4基因多态性与中国汉族血友病A患者血浆凝血因子Ⅷ抑制物发生的相关性研究

目的 探讨中国汉族血友病A(HA)患者肿瘤坏死因子α(TNF-α)-308基因多态性及细胞毒性T淋巴细胞相关抗原4(CTLA-4)-318基因多态性与凝血因子Ⅷ(FⅧ)抑制物的相关性.方法 采用聚合酶链反应结合限制性内切酶片段长度多态性(PCR-RFLP),对140例经过FⅧ替代治疗的HA患者和108名正常对照者的TNF-α及CTLA-4基因的单碱基多态性进行检测.所有HA患者样本均应用改良的Nijmegen方法检测FⅧ抑制物活性.结果 在HA患者中,TNF-α-308 G/G基因型118例(84.3%),G/A基因型18例(12.8%),A/A基因型4例(2.9%);CTLA-4-318 C/C基因型108例(77.2%),C/T基因型30例(21.4%),T/T基因型2例(1.4%).TNF-α-308、CTLA-4-318等位基因频率在HA病例组与正常对照组间差异均无统计学意义(P＞0.05),关联分析显示携带TNF-α-308 A等位基因HA患者发生FⅧ抑制物的风险是非A等位基因携带患者的7.519倍(OR=7.519,95%CI=3.168～17.844);而携带TNF-α-308 A等位基因重型HA患者发生FⅧ抑制物的风险是非A等位基因携带重型患者的8.163倍(OR=8.163,95%CI=2.521～26.434).携带CTLA-4-318 T等位基因血友病A患者发生FⅧ抑制物的风险与非T等位基因携带患者的差异无统计学意义(OR=1.586,95%CI=0.729～3.450).结论 TNF-α-308基因多态性与中国汉族人群重型HA患者发生FⅧ抑制物具有相关性,该基因可能为HA患者替代治疗产生抑制物的调节基因之一.

Abstract：

Objective To investigate the potential association between factor Ⅷ inhibitor development and polymorphisms of tumor necrosis factor-α(TNF-α)-308 and cytotoxic T-lymphocyte associated protein-4 gene in Chinese Han patients with hemophilia A(HA). Methods The single base change polymorphism in TNF-α and CTLA-4 gene was analyzed in 140 Chinese Han patients with hemophilia A who have been treated with plasma-derived FⅧ concentrates and 108 normal controls by using PCR-restrictive fragment length polymorphism(RFLP). All of the HA patients' plasma samples were measured by modified-Nijmegen assay simultaneously. Results In HA patients,G/G genotype,G/A genotype and A/A genotype were detected in 118 (84.3%) ,18( 12.8% ) and 4 cases(2.9% )respectively; C/C genotype,C/T genotype and T/T genotype were detected in 108(77.2% ), 30 (21.4%) and 2 cases( 1.4% )respectively. The difference in the genotype frequencies between HA patients and controls was nonsignificant ( P ＞ 0.05 ). Patients who were carriers of homozygotes for A allele had a higher risk of inhibitor development compared with those who were not( OR =7. 519, 95% CI = 3. 168 - 17. 844). Severe HA patients who were carriers of homozygotes for A allele had a higher risk of inhibitor development compared with those who were not ( OR =8. 163, 95% CI =2.521 -26. 434 ). There was no statistical difference in the risk of inhibitor development between the patients who were carriers or not ( OR = 1. 586, 95% CI = 0. 729 - 3. 450 ). Conclusion TNF-α-308 gene polymorphism is significantly associated with inhibitor development in Chinese Han patients with severe hemophilia A. TNF-α gene may be a useful marker and potential modulator of the immune response to replacement therapy for hemophilia A patients.