SIP1基因编码区点突变及多态性在先天性巨结肠症中的检测与分析

目的 检测先天性巨结肠症(Hirschsprung disease,HSCR)患者SIP1(Smad-interacting protein 1)基因编码区点突变及单核苷酸多态性特点,探讨SIP1基因与HSCR的关系.方法 应用聚合酶链反应.单链构像多态性(polymerase chain reaction-single strand conformation polymorphism,PCR-SSCP)和DNA直接测序技术,对50例HSCR、30名正常对照外周血SIP1基因编码区的10个外显子,进行点突变与单核苷酸多态性的检测与分析.结果 HSCR与正常对照突变图谱比较,有1例病例在第7外显子出现杂合性缺失,密码子157位点GTG→GTA置换,引起亮氨酸的同义突变,属于单核苷酸多态性,突变率为2%(1/50).有4例患者在第8外显子出现突变,突变率为8%(4/50).PCR-SSCP银染分析,第2外显子2例出现相同类型泳动变位;第7外显子3例出现相同类型泳动变位;第8外显子7例出现相同类型泳动变位.结论 HSCR有SIP1基因突变,提示SIPI基因与HSCR的发病存在一定程度的关联.     

AXIN2基因三个位点与先天性巨结肠的关联研究

目的 探讨AXIN2基因单核苷酸多态性(single nucleotide polymorphisms,SNPs)rs2240308、rs8081536和rs9913621 3个位点与先天性巨结肠(Hirschspnmg disease,HSCR)的关联性.方法 对120例HSCR患者和120名正常人群外周血进行基因组DNA抽提,用PCR技术对AXe2基因3个位点(rs2240308、rs8081536和rs9913621)进行PCR扩增,PCR产物用内切酶CviJ I、Dde I和BaN I消化,将SNPs位点进行分型与分析,应用X2检验统计分析病例组和对照组等位基因频率、等位基因型频率及其患病风险;同时将PCR产物进行测序,以进一步确定基因突变位点.结果 HSCR组与对照组AXIN2 rs8081536 CC和CT基因型频率差异无统计学意义(P＞0.05);而HSCR组与对照组AXIN2 rs2240308 GG、AG和从基因型频率及A和G等位基因频率差异有统计学意义(P＜0.05),GC和从基因型及G等位基因的患病风险分别为2.091、0.846和1.703;HSCR组与对照组AXIN2 rs9913621 CC、CT和TT基因型频率及C和T等位基因频率差异有统计学意义(P＜0.05),CC和TT基因型及T等位基因的患病风险分别为0.535、1.113和1.569.测序rs2240308第301位密码子核苷酸GCA→CCA杂合突变;rs913621第199位密码子核苷酸CAC→CAG杂合突变.结论 AXIN2 rs8081536等位基因变异与HSCR的易感性无关;AXIN2 rs2240308和rs9913621与HSCR的发生可能有关联,具有GG基因型与CC基因型患HSCR的危险性相对较高.     

Specific polymorphisms in the RET proto-oncogene are over-represented in patients with Hirschsprung disease and may represent loci modifying phenotypic expression

Hirschsprung disease (HSCR) is a common genetic disorder presenting with functional intestinal obstruction secondary to enteric aganglionosis. HSCR can be familial or sporadic. Although five putative susceptibility genes have been identified, only germline mutations in the RET proto-oncogene account for a significant minority (up to 50%) of familial HSCR; 3% of sporadic HSCR in a population based series carry RET mutations. From 1998 to February 1999, we prospectively ascertained 64 cases of sporadic HSCR from the western Andalusia region. To determine if polymorphic sequence variants within RET could act as low penetrance predisposing alleles, we examined allelic frequencies at seven polymorphic loci in this population based series. Whether allele frequencies differed from those in the control population were determined by either chi-squared analysis or Fisher's exact test. For two sequence variants, A45A (c 135G-->A) (exon 2) and L769L (c 2307T-->G) (exon 13), the rarer polymorphic allele was over-represented among HSCR cases versus controls (p<0.0006). In contrast, two other polymorphisms, G691S (c 2071C-->A) (exon 11) and S904S (c 2712C-->G) (exon 15), were under-represented in the HSCR patients compared to controls (p=0.02). Polymorphisms in the RET proto-oncogene appear to predispose to HSCR in a complex, low penetrance fashion and may also modify phenotypic expression.     

Intercellular adhesion molecule 1 K469E gene polymorphism is associated with presence of skin lesions in Tunisian Behçet's disease patients

Abstract
Intercellular adhesion molecule 1 ( ICAM1 ) gene polymorphisms have been implicated in the susceptibility to inflammatory diseases. The expression of both soluble and tissue ICAM1 were increased in Behçet's disease (BD) but the contribution of ICAM1 gene polymorphisms to this disease remains unknown. We sought to establish the association of ICAM1 gene K469E polymorphism in exon 6 with susceptibility for BD. One hundred and thirty-five Tunisian patients who satisfied the International Study Group criteria for BD and 157 healthy blood donor controls from the same geographic area were genotyped by polymerase chain reaction method for the K469E ICAM1 gene polymorphisms in exon 6. There were no significant differences in the distribution of the K469E allele or genotype frequencies between the BD patients and healthy controls in the ICA1 gene. Among patients, significant association was found between the presence of skin lesions and the studied polymorphism in the distribution of the K469E allele ( P = 0.004; odds ratio = 1.26; 95% confidence interval = 2.13–3.62) and genotype frequencies ( P = 0.0028;χ² = 11.75). Our findings suggest that K469E ICAM1 gene polymorphism was associated with Tunisian BD patients with skin lesions.     

Lack of association of vitamin D receptor gene polymorphisms with susceptibility to type 1 diabetes mellitus in the Portuguese population

The vitamin D receptor (VDR) gene is a candidate gene for susceptibility to autoimmune disorders. Association studies of VDR polymorphisms and risk of type 1 diabetes often produced conflicting results in different ethnic backgrounds. The aim of this study was to test for association between common VDR polymorphisms and the genetic susceptibility to type 1 diabetes in the Portuguese population. We genotyped 207 patients with type 1 diabetes and 249 controls for the FokI T>C (rs10735810), BsmI A>G (rs1544410), ApaI G>T (rs7975232), and TaqI C>T (rs731236) single nucleotide polymorphisms by polymerase chain reaction and restriction fragment length polymorphism analysis. The distribution of VDR genotype, allele, and haplotype frequencies did not differ significantly between patients and controls. These data suggest that the single nucleotide polymorphisms of the VDR gene are unlikely to contribute significantly to type 1 diabetes susceptibility in the Portuguese population.     

Mutations in Smad-interacting protein 1 gene are responsible for absence of its expression in Hirschsprung’s disease

Hirschsprung’s disease (HSCR) is a common congenital malformation of the enteric nervous system. The pathophysiological basis remains unclear. Recently, the SIP1 gene has been recognized as being involved in the pathogenesis of symptomatic HSCR patients with 2q22 chromosomal rearrangement. In this study, mutations in SIP1 were analyzed to explore the relationship between SIP1 and HSCR. All exons of SIP1 were amplified and then analyzed by PCR–restriction fragment length polymorphism (PCR–RFLP) and DNA sequencing. SIP1 expression was determined by immunohistochemistry, Western blot and real-time quantitative PCR. By PCR–RFLP, three different electrophoretic bands of 536, 428 and 257 bp representing different genotypes were demonstrated accordingly. DNA sequencing revealed a heterozygous absence of codon 157 GTG?→?GTA exchange at exon 7. Simultaneously, exchanges of GCC?→?ACC at codon 351 and ACC?→?GCC at codon 395 were also observed in exon 8. All the exchanges caused a missense mutation. By immunohistochemistry, SIP1 was ectopically expressed in the aganglionic segment of HSCR without mutation. For comparison, in HSCR with mutation either in exon 7 or exon 8, SIP1 immunoreactivity disappeared in all structures. The protein and mRNA levels determined by Western blot and real-time quantitative PCR were consistent with that of immunohistochemistry. In summary, mutations of the SIP1 gene were detected in HSCR. These mutations in SIP1 were responsible for the absence of its expression in HSCR and contributed to the pathogenesis of this disease.     

Associations between CD36 gene polymorphisms and susceptibility to coronary artery heart disease

Associations between polymorphisms of the CD36 gene and susceptibility to coronary artery heart disease (CHD) are not clear. We assessed allele frequencies and genotype distributions of CD36 gene polymorphisms in 112 CHD patients and 129 control patients using semi-quantitative polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. Additionally, we detected CD36 mRNA expression by real-time quantitative PCR, and we quantified plasma levels of oxidized low-density lipoprotein (ox-LDL) using an enzyme-linked immunosorbent assay (ELISA). There were no significant differences between the two groups (P>0.05) in allele frequencies of rs1761667 or in genotype distribution and allele frequencies of rs3173798. The genotype distribution of rs1761667 significantly differed between CHD patients and controls (P=0.034), with a significantly higher frequency of the AG genotype in the CHD group compared to the control group (P=0.011). The plasma levels of ox-LDL in patients with the AG genotype were remarkably higher than those with the GG and AA genotypes (P=0.010). In a randomized sample taken from patients in the two groups, the CD36 mRNA expression of the CHD patients was higher than that of the controls. In CHD patients, the CD36 mRNA expression in AG genotype patients was remarkably higher than in those with an AA genotype (P=0.005). After adjusted logistic regression analysis, the AG genotype of rs1761667 was associated with an increased risk of CHD (OR=2.337, 95% CI=1.336-4.087, P=0.003). In conclusion, the rs1761667 polymorphism may be closely associated with developing CHD in the Chongqing Han population of China, and an AG genotype may be a genetic susceptibility factor for CHD.     

PATZ1基因单核苷酸多态性与无精症的关系

目的 研究PATZ1基因的4个单核苷酸多态性(single nucleotide polymorphism,SNP)rs2240424、rs2057951、rs2240427和rs714909的多态性与无精症的关系.方法 用PCR-限制性片段长度多态性分析方法,在180例无精症患者和190名正常男性中对上述4个SNP位点的基因频率和基因型频率分布进行调查.结果 rs2057951位点的等位基因C(35.0%vs.27.6%,P=0.031)和带有等位基因C个体(CT+CC)(57.8%vs.46.3%,P=0.027)的频率在无精症患者显著高于正常男性.4种SNP的单倍型在两组人群中的分布差异有统计学意义(P=0.01),单倍型ACAC(11.1%vs.6.6%,P=0.029)和ACGC(11.2%vs.5.2%,P=0.003)在无精症患者中显著高于正常男性.结论 PTAZ1的rs2057951位点的等位基因C和单倍型ACAC和ACGC增加无精症的易感性,提示PTAZ1基因可能与无精症发病相关.     

中国广西地区健康人群E-选择素基因rs5359A/G、rs4786G/A多态性分析

目的:研究E-选择素基因单核苷酸多态性(SNP)rs5359A/G、rs4786G/A等位基因及其基因型在中国广西地区健康人群中的分布频率,并与其他种族和地区间的分布进行比较。方法:应用单碱基延伸PCR技术和DNA测序方法检测199例中国广西人群E-选择素基因rs5359A/G、rs4786G/A的多态性,并与人类基因组计划(Hapmap)公布的欧洲、非洲、日本和中国北京人群的基因型及等位基因的频率进行比较分析。结果:E-选择素基因rs5359A/G、rs4786G/A存在多态性,其基因型及等位基因频率在广西地区男女组间及与非洲、日本、中国北京人群比较无统计学差异(P>0.05),但与欧洲人群比较差异有统计学意义(P<0.05)。结论:中国广西地区健康人群E-选择素基因rs5359A/G、rs4786G/A存在多态性,与欧洲人群比较存在显著性差异,这种差异对于人类学研究可能起到重要作用。     

The promoter polymorphisms of receptor for advanced glycation end products were associated with the susceptibility and progression of sepsis

Receptor for advanced glycation end products (RAGE) is considered a major pattern recognition receptor, which plays an important role in the development of sepsis. Increasing evidence showed an association between RAGE polymorphisms and the susceptibility to several inflammatory‐related diseases. However, little is known about the clinical relationship between RAGE polymorphisms and sepsis. In this study, we analyzed the association of sepsis with three functional RAGE gene polymorphisms (rs1800624, rs1800625 and rs2070600) in a Chinese Han population (372 sepsis cases and 400 healthy controls). Significant differences were observed in the rs1800624 and rs1800625 genotype/allele distributions between the sepsis and controls, but no significant difference was observed in the rs2070600 genotype/allele. Moreover, our results also revealed a significant difference in the genotype/allele frequencies of the rs1800624 and rs1800625 polymorphisms between the sepsis and severe sepsis subtypes, the rs1800624 TT or rs1800625 TT genotype carriers exhibited a significant increase in RAGE mRNA, sRAGE, TNF‐α and IL‐6 expression compared with the rs1800624 AT/AA or rs1800625 CT/CC carriers in sepsis patients. Overall, this study might provide valuable clinical evidence between the RAGE gene polymorphisms and the risk or the development of sepsis.     

Opposed independent effects and epistasis in the complex association of IRF5 to SLE

Genetic variation in the interferon regulatory factor 5 (IRF5) gene affects systemic lupus erythematosus (SLE) susceptibility. However, association is complex and incompletely defined. We obtained fourteen European sample collections with a total of 1383 SLE patients and 1614 controls to better define the role of the different IRF5 variants. Eleven polymorphisms were studied, including nine tag single nucleotide polymorphisms (SNPs) and two extra functional polymorphisms. Two tag SNPs showed independent and opposed associations: susceptibility (rs10488631, P<10(-17)) and protection (rs729302, P<10(-6)). Haplotype analyses showed that the susceptibility haplotype, identified by the minor allele of rs10488631, can be due to epistasis between three IRF5 functional polymorphisms. These polymorphisms determine increased mRNA expression, a splice variant with a different exon 1 and a longer proline-rich region in exon 6. This result is striking as none of the three polymorphisms had an independent effect on their own. Protection was independent of these polymorphisms and seemed to reside in the 5' side of the gene. In conclusion, our results help to understand the role of the IRF5 locus in SLE susceptibility by clearly separating protection from susceptibility as caused by independent polymorphisms. In addition, we have found evidence for epistasis between known functional polymorphisms for the susceptibility effect.     

中国大陆汉族人群强直性脊柱炎患者骨保护素基因多态性研究

目的：通过骨保护素（OPG）基因单核苷酸多态性（SNPs）位点的筛查,分析中国大陆汉族人群中OPG基因多态性与强直性脊柱炎（AS）易感性的相关性。方法：采集2008年1月至2012年1月在我院就诊的AS患者195例（AS组）及203例性别、年龄与之匹配的健康体检者（对照组）的外周血样本,并提取基因组DNA。所有样本采用TaqMan探针法对OPG基因SNP rs2073618、rs4355801位点进行基因型鉴定。比较AS组与对照组之间不同等位基因及基因型的分布差异,并分析其与AS易感性的相关性。结果：OPG基因SNP rs2073618、rs4355801位点的等位基因及基因型分布均符合Hardy—Weinberg平衡。AS组与对照组等位基因频率分别如下。rs2073618（G）：71．0％、71．9％,（C）：29．0％、28．1％;rs4355801（G）：27．7％、26．4％,（A）：72．3％、73．6％。两组在基因型频率的分布上显示,m2073618（CC）：9．2％、8．9％,（GC）：39．5％、38．4％,（GG）：51．3％、52．7％;rs4355801（AA）：52．3％、52．7％,（AG）：40．0％、41．9％,（GG）：7．7％、5．4％。以上数据组间比较差异均无统计学意义（P〉0．05）。经关联性分析,未发现AS发病的风险等位基因或基因型。结论：中国大陆汉族人群中OPG基因SNP rs2073618、rs4355801单核苷酸多态性与AS的易感性之间没有相关性。     

白细胞介素16基因多态性与广西地区汉族女性膝关节原发性骨性关节炎的易感关联

背景：目前的基因研究表明,膝关节原发性骨性关节炎的发病风险与白细胞介素类基因有关联性。 目的：观察白细胞介素16基因多态性与女性膝关节原发性骨性关节炎的相关性。 方法：收集71例Kellgren/Lawrence评分大于2分的膝关节原发性骨性关节炎患者及85例健康对照的广西汉族女性的静脉血标本,采用聚合酶链反应-限制性片段长度多态性技术对两组白细胞介素16的 rs11556218,rs4072111,rs4778889多态位点进行基因分型,计算两组基因型和等位基因的分布差异,分析白细胞介素16基因多态性与膝骨性关节炎的易感关联。 结果与结论：两组3个SNP位点的各基因频数在两组中的分布符合Hardy-Weinberg平衡,等位基因比较差异无显著性意义。单个位点显性模式非条件Logistic回归显示,在rs11556218的3种基因型的比较中,T/G基因型较T/T基因型的膝原发性骨性关节炎的发病风险显著减低(OR=0.41,95%CI：0.21~0.83,P=0.02);在rs4072111中,C/T基因型比C/C基因型的发病风险显著增加(OR=2.36,95%CI：1.19~4.68,P=0.03)。结果证实,广西地区汉族女性人群白细胞介素16的遗传变异与膝关节原发性骨性关节炎的易感性关联。     

KIR2DL4 expression rather than its single nucleotide polymorphisms correlates with pre-eclampsia

Objective: To evaluate the single nucleotide polymorphisms and expression of KIR2DL4 (killer cell immunoglobulin-like receptors) gene in pre-eclampsia patients. Methods: KIR2DL4 gene polymorphisms were detected in 100 patients with pre-eclampsia and 100 healthy pregnant women, respectively, by using PCR-SS. Then, the expression of KIR2DL4 was measured in 5 cases of placentas tissues with pre-eclampsia and normal pregnancies by using qRT-PCR. Results: Compared with healthy controls, 16 loci of single nucleotide polymorphisms (SNP) were identified in pre-eclampsia patients, including 7 new polymorphisms loci. But, no significant difference was found in genotype distributions and allele frequencies in pre-eclampsia and controls (P>0.05). However, qRT-PCR results showed that KIR2DL4 mRNA in placenta tissues with pre-eclampsia was significantly lower than those with normal pregnancy, and the difference was statistically significant. Conclusion: Decreased level of KIR2DL4 rather than its SNP is correlated with the susceptibility of pre-eclampsia.     

Low RET mutation frequency and polymorphism analysis of the RET and EDNRB genes in patients with Hirschsprung disease in Taiwan

Hirschsprung disease (HSCR), or congenital intestinal aganglionosis, is a relatively common disorder characterized by the absence of ganglion cells in the nerve plexuses of the lower digestive tract, resulting in intestinal obstruction in neonates. Mutations in genes of the RET receptor tyrosine kinase and endothelin receptor B (EDNRB) signaling pathways have been shown to be associated in HSCR patients. In this study, we collected genomic DNA samples from 55 HSCR patients in central Taiwan and analyzed the coding regions of the RET and EDNRB genes by PCR amplification and DNA sequencing. In the 55 patients, an A to G transition was detected in two (identical twin brothers). The mutation was at the end of RET exon 19 at codon 1062 (Y1062C), a reported critical site for the signaling pathways. Single nucleotide polymorphisms (SNP) in exons 2, 7, 11, 13, and 15 of RET and exon 4 of EDNRB in the HSCR patients or controls were detected. The differences between patients and controls in allele distribution of the five RET polymorphic sites were statistically significant. The most frequent genotype encompassing exons 2 and 13 SNPs (the polymorphic sites with the highest percentage of heterozygotes) was AA/GG in patients, which was different from the AG/GT in the normal controls. Transmission disequilibrium was observed in exons 2, 7, and 13, indicating nonrandom association of the susceptibility alleles with the disease in the patients. This study represents the first comprehensive genetic analysis of HSCR disease in Taiwan.     

MBL2 gene polymorphisms related to HIV-1 infection susceptibility and treatment response

Human Mannose-binding lectin (MBL) is a protein encoded by MBL2 gene involved in the activation of the lectin-complement pathway. Several studies emphasized the role of MBL2 gene in several infectious diseases’ susceptibility, including HIV-1 infection. We aim to investigate the impact of 10 MBL2 gene polymorphisms located in the promoter, 5′UTR and exon 1 regions on HIV-1 physiopathology. The polymorphisms genotyping of 400 individuals, which 200 were HIV-1 positive patients and 200 were controls, was performed by PCR-sequencing. Our results showed that rs503037 and rs1800451 polymorphisms are associated with a high risk of HIV-1 infection susceptibility while rs7096206 and rs11003123 showed a protective effect. A significant association between haplotype CGA and HIV-1 infection susceptibility was also found in the exon 1 region. Moreover, rs11003124, rs7084554, rs36014597 and rs11003123 polymorphisms revealed an association with treatment response outcome as measured by RNA viral load. This study highlights the importance of MBL2 polymorphisms in the modulation of HIV-1 infection susceptibility and the contribution to treatment response outcomes among Moroccan subjects.     

广西人群miRNA-107基因多态性分布特征及其与血脂的关系

目的探讨miR-107基因单核苷酸多态性(SNP)位点rs2296616 C/T在广西地区健康人群中的分布特点,对比其在不同种族间基因型及等位基因频率分布的差异,并进一步探讨rs2296616 C/T位点单核苷酸多态性(SNP)与血脂水平的相关性。方法采用多重单碱基延伸SNP分型技术(multiplex SNa Pshot)和DNA测序法,检测372例广西健康人rs2296616 C/T位点的多态性,用7600生化仪检测其血脂相关指标,并用统计学方法分别比较rs2296616C/T位点多态性在各种族人群间的分布差异及不同基因型间的血脂水平差异。结果广西人群miR-107基因rs2296616 C/T位点存在TT(91.1%)和CT(8.9%)两种基因型及T(95.6%)和C(4.4%)两种等位基因。该位点的基因型和等位基因型频率在广西人群不同性别间的比较,差异无统计学意义(P>0.05)。其基因型和等位基因频率与人类基因组单体型图(Hap Map)所公布的欧洲人、日本人、非洲人、印第安人和墨西哥人分型数据相比较,差异均有统计学意义(P<0.05),但与北京汉族人群比较,差异无统计学意义(P>0.05)。rs2296616 C/T位点两种基因型人群血脂之间比较,携带TT基因型人群的高密度脂蛋白胆固醇(HDL-C)与CT组比较,差异具有统计学意义(P<0.05)。结论广西人群miR-107基因rs2296616 C/T位点多态性与其他种族人群之间比较存在不同程度的差异;rs2296616 C/T位点多态性与HDL-C水平高低有关。     

广西百色地区壮族妇女脂联素基因单核苷酸多态性与骨密度的关系

目的 探讨脂联素(APN)基因5个单核苷酸多态性(SNPs)与广西百色地区壮族妇女骨矿物质密度(BMD)的关系.方法 选取壮族女性239例跟骨骨量减少患者(LBM)和83例正常骨量组(NBM)进行病例对照研究,采用多重单碱基延伸SNP分型技术对壮族女性脂联素基因的5个位点(rs1063539、rs12495941、rs266729 、rs3774261 及rs710445)进行了基因分型,采用法国生产的Osteospace干式超声骨密度仪测量右侧跟骨超声振幅衰减(BUA).结果 仅rs1063539、rs12495941、rs266729及rs710445多态性分布符合Hardy-Weinberg遗传平衡定律(P>0.05).除rs3774261在骨量正常组的分布不符合Hardy-Weinberg平衡(P<0.05)之外,其余位点在正常组和骨量减少组基因型分布均符合Hardy-Weinberg平衡(P>0.05).其中,只有rs1063539 基因型在NOR和LBM组差异存在显著性(P=0.003),CG基因型者在LBM组人数明显多于GG型(P<0.01).调整年龄、体重、身高及体质指数后,以5个多态性位点作为自变量的多元 Logistic回归显示,仅rs1063539多态性与跟骨BUA相关性有统计学意义(adjusted OR=3.210,95%CI:1.631～6.137,P=0.001),并独立于骨量减少的传统危险因素.结论 APN基因第3外显子rs1063539多态性与壮族女性 BMD有一定关联,其中GG型对BMD具有一定的保护作用,CG型是BMD降低的危险因素.rs12495941、rs266729、rs3774261及rs710445多态性与壮族女性BMD无相关性.     

RET基因调控区遗传变异与先天性巨结肠患病风险研究

目的先天性巨结肠（HSCR）是一种复杂的先天性疾病,RET是其主要的易感性基因。本研究对RET非编码区单核甘酸多态性（SNP）-5G〉A（rs10900296）,-1A〉C（rs10900297）和intron1 C〉T（rs2435357）进行分型分析,评估RET基因调控区SNPs及单倍型与先天性巨结肠之间的相关性。方法选取115名病例组病人和139名对照组正常人群,应用聚合酶链反应（PCR）技术和直接测序的方法进行基因分型。回归模型中使用OR值和95%置信区间（CI）作为基因型危险性的评价指标。结果 -5G〉A,-1A〉C,intron1C〉T各基因型频率在病例和对照人群的分布具有显著差异。-5 AA（OR=6.26,95%CI=3.62-10.83）,-1 CC（OR=7.54,95%CI=2.06-27.66）和intron1 TT（OR=19.22,95% CI=7.54-48.99）基因型均能显著增加HSCR发病的风险。单倍型A-C-T（OR=6.28,95% CI=3.77-10.46）和双体型A-C-T/A-C-T（OR=13.62,95% CI=3.48-53.30）分析同样表明与HSCR发病风险存在较强的相关性,并呈现出一定的累积效应。结论 RET基因调控区的基因多态性可能与HSCR的发病易感性有关,支持RET通路的常见变异在HSCR的发展过程中起着重要的作用的假设。     

Semaphorin-3A,semaphorin-7A gene single nucleotide polymorphisms,and systemic lupus erythematosus susceptibility

Abstract

Background: Semaphorin-3A (Sema3A) and Semaphorin-7A (Sema7A) play crucial roles in immune system by inhibiting T cell proliferation and leading to the secretion of pro-inflammatory cytokines. Increasing evidence suggest that Sema3A and Sema7A may link to the development and pathogenesis of systemic lupus erythematosus (SLE).

Objective: This study aims to evaluate the association of Sema3A, Sema7A gene single-nucleotide polymorphisms (SNPs) with susceptibility to SLE.

Methods: There were 495 SLE patients and 493 healthy controls in the study. Sema3A gene and Sema7A gene were genotyped by improved multiple ligase detection reaction (iMLDR), their plasma expression levels were detected by enzyme-linked immunosorbent assay (ELISA).

Results: No differences in genotype and allele frequencies of these SNPs were observed between SLE patients and healthy controls. However, analysing Sema3A and Sema7A SNPs with clinical manifestations of SLE indicated that, in Sema3A, the A allele frequencies of rs7804122 polymorphism was higher in patients with oral ulcers. In Sema7A, there were differences in allele frequencies of the rs2075589 and rs28362930 polymorphisms between SLE patients with haematological disorder and those without. The GG genotype and G allele frequencies of rs28362930 and the CC genotype, and C allele frequencies of rs741761 were both related to discoid rash in SLE patients. The allele frequency of G (rs28362930) was higher in SLE patients with renal disorder. There were differences in the genotype frequencies and allele frequencies of rs741761 between SLE patients with and without arthritis. No differences in plasma Sema3A and Sema7A levels were detected in SLE patients of different genotypes.

Conclusions: Sema3A and Sema7A gene polymorphisms are not related to SLE genetic susceptibility, but may link to several clinical features of SLE.