FOXO3 rs12212067: T > G Association with Active Tuberculosis in Han Chinese Population

It is well known that the human innate immune and adaptive immune response play important role in tuberculosis (TB) infection and progress. Emerging evidence shows that FOXO3 plays an important role in the human immune system. Recent research has shown that the FOXO3 genetic variants are associated malaria infection. In this study, 268 confirmed TB patients, 321 patients with latent tuberculosis infection (LTBI), and 475 TB-free controls were recruited; the single-nucleotide polymorphism (SNP) rs12212067: T > G in FOXO3 was genotyped using predesigned TaqMan® allelic discrimination assays. The results showed that the G allele of rs12212067 in FOXO3 was more common in health control and the latent TB group compared with the active TB group (p?=?0.048, odds ratio (OR) 95 % confidence intervals (CI)?=?1.37 (1.00–1.89); p?=?0.042, OR 95 % CI?=?1.42 (1.01–1.99), respectively); furthermore, within active TB patients, the G allele of rs12212067 in FOXO3 was more frequent in extra-pulmonary tuberculosis (EPTB) group compared to pulmonary tuberculosis (PTB) group (p?=?0.035, OR 95 % CI?=?0.57 (0.33–0.97). In conclusion, this study found that rs12212067 in FOXO3 was associated with increased risk of active TB. The minor G allele might be a protection factor which was found more common in latent TB patients and healthy controls than active TB patients.     

BARD1单核苷酸多态性与汉族儿童神经母细胞瘤相关性的研究

目的 探讨BARD1单核苷酸多态性与汉族儿童神经母细胞瘤的相关性.方法 采用病例对照研究,收集242例汉族神经母细胞瘤患儿及301例汉族健康儿童的外周血,通过PCR方法扩增目的DNA,应用Sequenom massarray对所扩增的DNA进行基因分型.以x2检验及logistics分析比较不同组基因型与神经母细胞瘤的关系.结果 BARD1的21个标签SNPs位点均符合Hardy-Weinberg平衡,BARD1的21个SNPs等位基因频率在患者组与对照组之间差异均无统计学意义(P＞0.05).结论 未发现BARD1单核苷酸多态性与汉族儿童神经母细胞瘤有相关性.     

Common Polymorphisms in the CACNA1H Gene Associated with Childhood Absence Epilepsy in Chinese Han Population

Variants with a relatively high frequency in the CACNA1H gene have previously been identified in cases of childhood absence epilepsy (CAE) in the Chinese Han population most of which are located in exons 6 to 12. In present study we attempted to further investigate whether the CACNA1H gene is associated with CAE. Exons 6 to 12 of CACNA1H gene were sequenced in samples of 100 CAE trios recruited consecutively, and 191 normal human controls. Single nucleotide polymorphisms (SNPs) were studied in both single locus and haplotype analyses in 218 CAE trios, of which 118 trios were selected from our previous research. Case-control comparisons and the transmission disequilibrium test (TDT) both supported a coding SNP (cSNP) rs9934839 (R603R) in exon 9 as being close related to CAE. The carriers of the G allele of rs9934839 had a 3-fold higher risk of CAE than non-carriers. Moreover, another cSNP rs8044363 was predicted to be connected directly with CAE in a Bayesian network. In addition, two haplotypes consisting of five cSNPs in the region of CACNA1H were statistically associated with CAE. Our research provides new evidence to further support the hypothesis that CACNA1H may be an important susceptibility gene for CAE in the Chinese Han population.     

HLA-DQB1基因多态性与中国汉族人群系统性红斑狼疮的相关性

目的 探讨HLA-DQB1基因单核苷酸多态性(single nucleotide polymorphisms,SNP)与汉族人群系统性红斑狼疮(systemic lupus erthematosus,SLE)遗传易感性的相关性.方法 通过聚合酶链式反应-连接酶检测反应(polymerase chain reaction-ligase detection reaction,PCR-LDR)技术对908例SLE患者和961例健康对照rs3129716(HLA-DQB1)位点进行基因分型,同时结合临床表现分型,分析该位点与疾病及临床表型的相关性.分型结果用PLINK1.07软件进行统计分析.结果 rs3129716(HLA-DQB1)位点等位基因频率和基因型频率在SLE疾病组和对照组的分布差异无统计学意义(P＞0.05).三种遗传模型下的分析显示,两组间差异无统计学意义(P＞0.05).将SLE患者按血清学指标及临床表现分型,未发现相关性.结论 rs3129716(HLA-DQB1)与中国汉族人群SLE患者遗传易感性不相关.     

汉族人群血管紧张素原基因的新单核苷酸多态性位点

应用改进的PCR－SSCP技术、多种聚丙烯酰胺凝胶电泳和PCR产物直接测序等方法,分析人的血管紧张素原（AGT）基因启动子区5远侧端的单核苷酸多态性（SNP）。在非变性胶上,发现不同样品的PCR产物（双链DNA分子）电泳迁移率不同;而在变性胶上,对应的单链DNA分子电泳迁移率相同;PCR产物直接测序的结果表明,在同一PCR扩增片段中同时存在两个SNPs位点（G－1074T,A－1179G）;通过476个不同样品的实验结果,进一步证实两个SNPs位点处于完全的连锁不平衡关系。GenBank同源性比较结果显示：A－1179G为中国汉族人群所特有。     

Genetic Variations in FTSJ1 Influence Cognitive Ability in Young Males in the Chinese Han Population

Human cognitive ability is a trait that is known to be significantly influenced by genetic factors. Previous linkage data provide evidence suggesting that gene FtsJ homolog 1 (Escherichia coli) is associated with mental retardation. The gene may have a relation to individual differences in cognitive ability because it is most critical for brain development. In the present research, three tag single-nucleotide polymorphism (SNPs) (rs2268954, rs2070991, and rs5905692) in FtsJ homolog 1 (E. coli) are selected and genotyped by the PCR-SSCP method. An analysis of variance is performed to determine the relationship between the SNPs and cognitive ability of the Chinese Han population of youth in Qinba mountain. There are significant correlations between the variance in FtsJ homolog 1 (E. coli) and general cognitive ability, verbal comprehension, and preceptual organization. These findings suggest that genetic variations in FtsJ homolog 1 (E. coli) possibly influence human cognitive ability.     

中国汉族人群IL-1RA基因多态性及其与宫颈癌的相关性研究

目的 研究位于白细胞介素1受体拮抗剂基因（interleukin-1 receptor antagonist, IL-1RA）第二个内含子中可变串连重复序列（variable number of tandem repeats, VNTR）多态性在中国3个汉族人群中的分布情况,并探讨其与宫颈癌的发生关系。方法 采用PCR方法分别对3个汉族人群206例个体以及42例宫颈癌患者和45例对照进行多态性检测,扩增产物进行2％的琼脂糖电泳。结果 三个汉族群体的基因型以A1/A1和A1/A2最为常见。等位基因以A1频率最高,A2次之,群体间的差异是不显著的（P＞0.05）。与美、英高加索人群相比,A1 的频率明显偏高,A2明显偏低,而与非洲黑人相近。在宫颈癌患者和正常对照人群中,该多态位点的等位基因和基因型频率均无统计学意义（P＞0.05）。结论 IL-1RA第二个内含子中 VNTR多态性在不同种族间的分布存在着明显的差异,但与中国东北地区宫颈癌的发生可能无直接相关性。     

Association of HSPA1B SNP rs6457452 with Alopecia Areata in the Korean Population

The heat shock 70?kDa protein 1B (HSPA1B), which has been well-studied among the famous heat shock proteins HSPA1A/B/L, is related to autoimmune diseases, including Alopecia Areata (AA). In this study, the association of a 5’-untranslated region (5’UTR) SNP rs6457452 and a promoter SNP rs2763979 (‐1140C?>?T) of HSPA1B with AA was investigated in 236 controls and 228 AA patients. Statistical analyses using the multiple logistic models were done, according to the onset and the clinical features of AA, including the age of onset, family history, type of AA lesion, nail involvement and body hair involvement. The results showed that rs6457452 was associated with the onset of AA (p?<?0.002). In the analysis of clinical features of AA, rs6457452 was weakly related to the age of onset (p?≤?0.04) and that rs2763979 was only weakly related to the type of AA lesion (p?=?0.041). In conclusion, we suggest that the 5’UTR SNP rs6457452 of HSPA1B may be associated with the onset of AA and the T allele of rs6457452 may confer the reduced susceptibility to AA in the Korean population.     

498例北京地区汉族人群脑梗死患者SLCO1B1和ApoE基因多态性分析

目的 了解北京地区汉族人群脑梗死患者中SLCO1B1和ApoE不同基因型的分布差异,从而对他汀类药物在脑梗死患者中的使用提供数据支持,为临床用药提供参考.方法 采用聚合酶链反应-荧光探针方法对2019年6月至2021年6月就诊于北京世纪坛医院且诊断为脑梗死的498例住院患者进行SLCO1B1和ApoE基因多态性检测.分析总体及不同性别SLCO1B1和ApoE基因多态性分布和基因型分布情况.结果 498例脑梗死患者中共检出6种SLCO1B1基因型,由多到少分别为?1b/?1b(36.95％),?1a/?1b(34.74％),?1b/?15(13.05％),?1a/?1a(9.84),?1a/?15(4.62％)和?15/?15(0.80％).共检出6种ApoE基因型,由多到少分别为E3/E3(71.08％),E2/E3(12.05％),E3/E4(14.06％),E2/E4(1.61％),E2/E2(0.60％)和E4/E4(0.60％).ApoE基因型分布结果在不同性别之间存在差异,且具有统计学意义(P<0.05).结论 本研究对北京地区汉族人群脑梗死患者的SLCO1B1和ApoE基因进行分析,发现ApoE基因型在汉族脑梗死患者不同性别中存在差异(P<0.05).本研究对脑梗死人群降低用药风险供了数据支持,对实现精准个体化及安全用药具有重要意义.     

The neck-region polymorphism of DC-SIGNR in peri-centenarian from Han Chinese Population

Background  

DC-SIGNR (also called CD209L) has been extensively studied on its role in host genetic predisposition to viral infection. In particular, variable number tandem repeat (VNTR) of the neck-region of DC-SIGNR is highly polymorphic and the polymorphism has been investigated for genetic predisposition to various infectious diseases, though conflicting results had been reported. As infection is a major cause of human death and a mechanism of natural selection, we hypothesized that VNTR polymorphism of DC-SIGNR might have an effect on human life span.     

糖皮质激素受体遗传多态性与2型糖尿病相关性研究

目的 探讨糖皮质激素受体(GR)单核苷酸多态性与2型糖尿病(T2MD)易感性及人体体型的相关性.方法 采用病例-对照研究设计,从解放军总医院健康体检中心的体检患者中,募集40例T2MD患者和127例对照.结合三种不同的SNP位点选择方法,采用上海天昊生物科技有限公司的iMLDRTM多重SNP分型技术对入选SNP位点进行基因分型.采用非条件Logistic回归,校正年龄、性别、吸烟、饮酒后,分析基因型与T2MD易感性的关系.得到的阳性位点,进一步采用协方差分析,校正年龄、性别、吸烟、饮酒后,评价其与体重指数(BMI)和腰臀比(WHR)的相关性.结果 共选取14个SNP位点,其中rs10052957突变型在病例组中频率为零,故未纳入统计分析.所有的13个SNP位点在病例和对照组中的基因分型均符合Hardy-Weinberg平衡.rs9324924 TT基因型(OR [95％CI]=3.12[1.06 ～9.17],P=0.039)和rs9324921 AA基因型(OR [95％CI]=14.92[1.39～160.60],P=0.026)发生T2DM的风险较野生型增高,且两基因型的BMI[P=0.023 (rs9324924);P=0.002(rs9324921)]、WHR[P=0.033 (rs9324924);P=0.003(rs9324921)]也较野生型明显增高.结论 在本研究中,GR基因rs9324924、rs9324921与T2DM易感性和体型有关,其中纯和突变型T2DM发病风险明显增加,且更具有肥胖倾向.     

SQSTM1 mutations in Han Chinese populations with sporadic amyotrophic lateral sclerosis

Mutations in the sequestosome 1 gene (SQSTM1) have recently been identified in patients with amyotrophic lateral sclerosis, accounting for 1.11%–4.92% of familial ALS and 2.42%–4.37% of sporadic amyotrophic lateral sclerosis (SALS). The mutation spectrum of SQSTM1 in Chinese patients with SALS remains unknown. Three hundred and six patients with SALS from the Department of Neurology, West China Hospital of Sichuan University were recruited for this study. From the same region, 350 healthy individuals were recruited as a control group. The encoding regions of SQSTM1 were screened by direct sequencing. Three novel nonsynonymous mutations— p. I99L, p. D337E, and p. L341V—were identified in 3 patients with SALS, none of which were found in healthy controls. The male patient carrying mutation p. I99L presented limb symptom at age of 34 and died in 34 months. Two late-onset patients carrying D337E and p. L341V mutations had bulbar and limb onset, respectively. Moreover, a c.1166-14_1166-11delTACT mutation in the intron 7 was found in a living male patient with limb onset at age of 62. None of the patients carrying SQSTM1 mutation showed clinical evidence of concomitant Paget disease of bone or mutation of the valosin-containing protein gene. The mutation frequency of SQSTM1 was 0.98% in Chinese patients with SALS, which was lower than those in other racial populations.     

A functional polymorphism in the SPINK5 gene is associated with asthma in a Chinese Han Population

Background  

Mutation in SPINK5 causes Netherton syndrome, a rare recessive skin disease that is accompanied by severe atopic manifestations including atopic dermatitis, allergic rhinitis, asthma, high serum IgE and hypereosinophilia. Recently, single nucleotide polymorphism (SNP) of the SPINK5 was shown to be significantly associated with atopy, atopic dermatitis, asthma, and total serum IgE. In order to determine the role of the SPINK5 in the development of asthma, a case-control study including 669 asthma patients and 711 healthy controls in Han Chinese was conducted.     

中国湖北地区IL-1RN内含子2基因多态性分布的研究

目的 :探讨湖北地区汉族健康人群白细胞介素 1受体拮抗剂(IL 1Ra)内含子 2基因多态性的分布 ,比较其在不同种族间分布的差异。方法 :采用PCR方法检测了 2 5 1例湖北地区汉族健康人群IL 1Ra基因内含子 2的可变数串联重复 (VNTR)多态性 ,并结合文献进行不同种族间的比较分析。结果 :湖北地区汉族健康人群基因型以Ⅰ /Ⅰ型最为常见 ,其次为Ⅰ /Ⅱ型 ,Ⅰ /Ⅳ和Ⅱ /Ⅱ型较为罕见 ,分布频率依次为 0 .813、0 .167、0 .0 16、0 .0 0 4;其等位基因以Ⅰ型最为常见 ,其次为Ⅱ型 ,Ⅳ型较为罕见。与美、德和日本等国家人群相比 ,该VNTR多态性均存在显著性差异 (P <0 .0 0 5 ) ,与国内江苏和重庆地区人群相比虽无显著性差异 (P >0 .0 5 ) ,但在湖北地区发现了较为罕见的Ⅰ /Ⅳ和Ⅱ /Ⅱ基因型。结论 :湖北地区汉族人群IL 1Ra基因内含子 2存在VNTR多态性 ,其在不同种族间的分布存在显著性差异     

江苏汉族人群XRCC1基因的遗传多态性研究

目的探讨江苏省汉族正常人群中X线修复交叉互补基因1（XRCC1）常见的两个单核苷酸多态（SNPs）C26304T和G27466A的遗传分布特点。方法采用聚合酶链反应（PCR）及限制性片段长度多态（RFLP）方法分析江苏省扬中地区511名健康汉族人的XRCC1基因C26304T和G27466A的基因多态性。结果511名江苏汉族人的XRCC1 C26304T基因型CC、CT、TT的频率分别为45．8％、42．7％和11．5％,等位基因C、T的频率分别为67．1％和32．9％。G27466A基因型GG、GA、AA的频率分别为68．9％、29．0％和2．1％,等位基因G、A的频率分别为83．4％和16．6％。江苏人群的C26304T基因型频率和等位基因频率分布与浙江、台湾人群均无明显差异（P〉0．05）,但与意大利人、美国白人、美国黑人的差异具有显著性（P〈0．05）。江苏人群的G27466A基因型频率和等位基因频率分布与浙江人、台湾人、意大利人、美国白人、美国黑人的差异均具有显著性（P〈0．05）。结论本研究揭示了江苏汉族人群XRCC1基因C26304T和G27466A的等位基因频率和基因型频率分布特点;证实了C26304T和G27466A位点的等位基因和基因型频率存在种族、地区差异。     

A Genetic Variant rs1020760at NFKB1 is Associated with Clinical Features of Psoriasis Vulgaris in a Han Chinese Population

Psoriasis vulgaris is a chronic inflammatory skin disease associated with complex genetic susceptibility. Recently, we identified a single‐nucleotide variant rs1020760 at NFKB1 significantly associated with psoriasis in a Han Chinese population in deep analysis of exome and targeted sequencing (P = 1.76 × 10^?8). To investigate the potential association between rs1020760 and phenotypes of psoriasis vulgaris, we performed a genotype–phenotype analysis. A total of 9946 cases and 9906 controls with detailed clinical and demographic information were involved in this study, while the genotype data of rs1020760 was available in the previous targeted sequencing study of psoriasis. Genotype‐based association testing revealed the additive model might provide the best fit for rs1020760 (P = 5.44 × 10^?8). Case‐only analysis showed that the distribution of allele G was significantly different between the cases with and without family history (P_allele = 4.07 × 10^?3,P_genotype = 5.75 × 10^?3). The differences in allele and genotype frequencies were observed between all the subphenotypes and controls except for the genotype frequency of the late onset subgroup, while no difference was found in case‐only analysis for the other two subphenotypes. Rs1020760 was preferentially associated with family history of psoriasis, implying that NFKB1 might not only play important roles in the development of psoriasis, but might also contribute to the special phenotypes of this disease.     

Associations of MMP1, 3, 9 and TIMP3 Genes Polymorphism with Isolated Systolic Hypertension in Chinese Han Population

Background and aims: Large artery stiffness and endothelial dysfunction are the predominant characteristic of isolated systolic hypertension. Recently studies have revealed MMP1, 3, 9 and TIMP3 Genes polymorphism were associated with arterial stiffness, but the relationship with isolated systolic hypertension were not further studied. This study was to investigate the associations of MMP1,3,9 and TIMP3 Genes polymorphism with isolated systolic hypertension. Methods: We identified the genotype of the genes in 503 patients with isolated systolic hypertension, 481 essential hypertension patients with elevated diastolic blood pressure and 244 age-matched normotensive controls for 5 SNPs and detected the brachial-ankle pulse wave velocity, flow-mediated dilatation, endothelin-1 and nitric oxide among the participants. Results: Multinomial logistic analyses showed that the 5A allele of rs3025058(5A/6A) in MMP3 and the T allele of rs3918242(C-1562T) in MMP9 were significantly associated with isolated systolic hypertension after adjusted by age, triglyceride, low-density lipoprotein (P<0.001, Pcorr<0.003; P=0.009, Pcorr=0.027). The 5A/G/C and 6A/A/T haplotypes were significantly associated with isolated systolic hypertension (Permutation p=0.0258; Permutation p=0.000002). In addition, the brachial-ankle pulse wave velocity of different genotypes for the 5A/6A and C-1562T polymorphisms was significantly highest in 5A or T homozygotes (P<0.01), however, the flow-mediated dilatation and nitric oxide were markedly lowest in 5A or T homozygotes (P<0.01). Conclusion: MMP3 and MMP9 genes variant seem to contribute to the development of isolated systolic hypertension by affecting arterial stiffness and endothelial function.     

CD11b单核苷酸多态性与中国汉族系统性红斑狼疮的研究

目的 分析CD11b基因rs1143679的单核苷酸多态性(SNP)在中国汉族系统性红斑狼疮(SLE)患者中的表达,并阐明该SNP与SLE临床表型的相关性.方法 采用病例对照的研究方法,应用PCR-PFLP以及直接测序技术对中国汉族人群中584例系统性红斑狼疮患者和624例健康对照者进行多态性检测,分析基因型和等位基因频率的分布差异,并与临床表型进行相关性分析.结果 (1)SLE患者中CD11b rs1143679 GA基因型频率为1.89％,大大低于欧美国家的基因型频率,与香港及泰国地区接近.(2) CD11b rs1143679 GA基因型与狼疮肾炎有相关性(P=0.01),而与发病时间、关节炎、血液系统、神经系统损害没有统计学差异(P＞0.05).结论 CD11b rs1143679 SNP与中国汉族人群系统性红斑狼疮易感性有关,并可能参与了狼疮肾炎的发生发展.     

Association Study of Serotonin Transporter Gene Polymorphisms with Obstructive Sleep Apnea Syndrome in Chinese Han Population

Background:

Since the serotonin (5-HT) is associated with circadian rhythm and breathing regulation, the serotonin transporter (5-HTT), which plays an important role in serotoninergic transmission, might be a strong candidate gene in the pathogenesis of obstructive sleep apnea syndrome (OSAS).

Objective:

To investigate the association of 5-HTT gene polymorphisms with OSAS and clinical characteristics.

Methods:

We genotyped the 5-HTT gene linked polymorphic region (5-HTTLPR) and a variable number of tandem repeats at intron 2 (STin2.VNTR) in 254 OSAS patients and 338 healthy controls in Chinese Han population.

Results:

In total sample, the 10-repeat allele of STin2.VNTR was significantly associated with OSAS (P = 0.007, OR = 1.72, 95% CI = 1.15~2.58), but no association was found in 5-HTTLPR. In male subjects, both polymorphisms showed significant association with OSAS (Allele L: P = 0.005, OR = 1.44, 95% CI = 1.11 to 1.87; Allele 10: P = 0.002, OR = 1.94, 95% CI = 1.26 to 3.00). Two haplotypes, S-12 and L-10, constructed by the above polymorphisms also revealed significant associations with OSAS (global P-values were 0.020 for total sample and 0.0006 for male subjects, respectively). Male patients carrying the haplotype S-12 showed a significantly lower apnea / hypopnea index (AHI), depressive factor, plasma 5-HT level and 5-hydroxyindolacetic acid (5-HIAA) levels, but higher episodic memory, when compared with non-S-12 carriers (P < 0.05). However, no significant differences were found in excessive daytime sleepiness or other psychological function across haplotype carriers (P > 0.05).

Conclusions:

These findings support that 5-HTT gene may be involved in susceptibility to OSAS, especially with sex-dependent effect.

Citation:

Yue W; Liu H; Zhang J; Zhang X; Wang X; Liu T; Liu P; Hao W. Association study of serotonin transporter gene polymorphisms with obstructive sleep apnea syndrome in chinese han population. SLEEP 2008;31(11):1535–1541.