先天性巨结肠症内皮素受体B基因的多态性研究

目的观察中国汉族散发性先天性巨结肠症（sHD）G蛋白藕联受体家族的内皮素受体-B（EDNRB）易感基因的突变与多态性特征，探讨碱基改变与先天性巨结肠症的发病关系。方法收集104例散发性先天性巨结肠与其中42例患儿（子代组）的双亲血样，120例正常儿童作对照，聚合酶链反应-单链构象多态性（PCR—SSCP）与DNA测序确定并比较EDNRB基因外显子1、2的突变与多态性位点（SNPs）等位基因与基因型分布差异，分析sHD表型与SNPs的关联，传递不平衡检验（TDT）分析三样本家系SNPs的传递不平衡。结果EDNRB基因外显子1、2均未发现突变，外显子1检测2个SNPs，c311A→T（N104I）为新发现位点；病例组c311A→T位点的等位基因和基因型频率均与对照组差异有统计学意义（P〈0．01），c99C→T位点的差异无统计学意义；TDT检验发现亲子代间在c311A→T（N104I）位点存在传递不平衡，杂合体双亲优先传递等位基因T给子代；临床表型与SNPs等位基因分布无明显关联。结论中国汉族散发性先天性巨结肠EDNRB基因的多态性可能在发病中起重要作用。     

雌激素受体β的单核苷酸多态性与前列腺癌风险的相关性研究

目的研究雌激素受体β(ERβ)的单核苷酸多态性(SNPs)与前列腺癌(CaP)风险的相关性。方法对40例CaP患者和86例正常对照者利用直接测序法对ERβ基因中的4个SNPs(近端启动子上游的3个SNPsrs3829768,rs1271572,rs3841304和外显子7上的SNPsrs1256049)进行基因分型,分析单个位点的等位基因和基因频率是否与CaP相关。结果由于不符合HardyWeinberg平衡,SNP位点rs3841304被排除。发现在CaP患者中,近端启动子上游的SNPs位点rs3829768(A/G)的G和rs1271572(C/A)的A等位基因频率及其基因型频率均显著低于正常对照者(P<0.01)。结论ERβ基因近端启动子上游有2个SNPs与汉族CaP之间存在显著的相关性。     

先天性巨结肠症内皮素B受体基因分析

目的　检测中国散发先天性巨结肠症 (HD )是否有EDNRB基因突变 ,以探讨EDNRB与HD发生的关系。方法　提取 3 4例中国散发性HD患儿手术切除的组织标本基因组DNA ,聚合酶链反应(PCR)扩增EDNRB基因第 3 ,4,6外显子 ,单链构象多态 (SSCP)分析上述外显子是否有突变。结果　13例短段型HD中 ,2例有EDNRB基因突变 ;常见型及长段型未见EDNRB基因突变。结论　中国散发短段型HD有EDNRB基因突变 ,提示EDNRB基因与先天性巨结肠症的发生有关。     

ACE2基因多态性与新疆墨玉县维吾尔族慢性肾脏病的关系

目的:探讨ACE2基因多态性与新疆维吾尔族成人CKD的关系。方法:在2013年03月~2014年04月新疆墨玉县农村维吾尔族成人慢性肾脏病(CKD)流行病学调查的数据库基础上,随机抽取资料完整的CKD及健康对照样本共254例,采用聚合酶连反应和限制性片段长度多态性(PCR-RFLP)分型技术对ACE2 G8790A、A1075G两位位点单个核酸多态性(SNPs)进行基因分型鉴定。结果:ACE2基因G8790A位点基因型及等位基因频率分布情况:在女性CKD组中AA基因型频率高于健康对照组(P0.05)。在男性CKD组中A等位基因频率高于健康对照组(P0.05)。ACE2基因A1075G位点基因型及等位基因频率分布情况:在女性CKD并高血压组中AA基因型频率高于非高血压组(P0.05)。结论:ACE2G8790A基因多态性可能与新疆维吾尔族成人CKD有关。ACE2 A1075G基因多态性可能与新疆维吾尔族女性成人CKD合并高血压有关。     

Megsin基因C25663G多态性与我国汉族人群IgA肾病的关系

目的:研究 Megsin基因C25663G多态性与我国汉族人群IgA肾病发生、发展的关系.方法:应用PCR-RFLP方法鉴定IgA肾病患者基因型,用以家庭为基础的传递不平衡检验(TDT)、单倍型相对危险度(HRR)分析结合病例-对照研究方法,分析Megsin基因C25663G多态性与我国汉族人群IgA肾病发生的关系.IgA肾病患者按病情是否稳定分为病情进展组和稳定组,比较两组间基因型分布频率差异.结果:TDT显示Megsin基因C25663G等位基因的传递在IgA肾病患者没有显著倾向性(χ2=0.203,P=0.652),HRR分析已传递和未传递等位基因频率无统计学差异(χ2=0.268,P=0.679),IgA肾病患者和正常对照者基因型和等位基因分布频率无统计学差异(P＞0.05).在IgA肾病进展组和稳定组之间,基因型分布频率无统计学差异(χ2=2.400,P=0.153).结论:Megsin基因C25663G多态性与中国汉族人群IgA肾病的发生及病情进展无关.     

TBX22基因多态性与非综合征性唇腭裂相关关系的研究

目的：探讨TBX22基因多态性与中国华东地区部分人群非综合性征唇腭裂的关系。方法：选取80个核心家庭的80例NSCL/P患儿为实验组;选取80例正常儿童作为对照组。分别提取患儿及其父母和正常儿童的外周血DNA。应用聚合酶链式反应（polymerase chain reaction,PCR）分别扩增TBX22基因编码区外显子3的全部序列（包含G359A、A361G突变位点）,然后运用DNA测序技术,检测华东地区核心家庭的TBX22基因编码区的突变情况,分析记录基因型。根据测序所得基因型数据,比较患者组与正常儿童的基因型和等位基因频率,并对核心家庭的数据进行单倍型相对风险分析（haplotype relative risk,HRR）,对父母至少一方为杂合子的核心家庭进行传递不平衡检验（transmitted disequilibrium test,TDT）。结果：TBX22基因A361G未检出多态性;G359A检测出基因多态性,实验组和对照组儿童进行病例对照研究发现基因型频数分布差异有统计学意义（P〈0.05）。而两组间单体型相对风险率的分析（HRR）和传递不平衡检验（TDT）结果均无统计学意义（P〉0.05）。结论：TBX22基因G359A位点多态性与中国华东地区部分人群NSCL/P的发生相关,可能是NSCL/P的易感基因。     

东北汉族人群中IRF6基因单核苷酸多态性与非综合征唇腭裂的相关性研究

目的探讨干扰素调节因子6基因rs2235371,rs2013162位点单核酸多态性与中国东北部人群的非综合征唇腭裂的相关l生。方法收集东北地区非综合征唇腭裂患儿165例,患者父亲109例,患者母亲118例,核心家系101例,对照组164例。采用聚合酶连一限制性片段长度多态性方法检测基因多态位点的基因型,进行病例对照和传递不平衡（TDT）分析。结果病例对照研究结果显示,单纯唇裂和唇腭裂rs2235371位点的GG基因型频率存在显著差异（P〈0．05）,而在单纯腭裂组比较,差异无统计学意义（P=0．11）。采用传递不平衡分析研究发现,干扰素调节因子6基因rs2235371位点的G等位基因在唇腭裂患者中存在过度传递（P〈0．05）,而在腭裂组没有统计学意义。rs2013162位点基因型无明显统计学意义。但c等位基因在单纯唇裂组与唇腭裂都存在过度传递。rs2235371与rs2013162位点的FBAT分析中未见统计学意义。结论干扰素调节因子6基因rs2235371位点G等位基因与东北人群的非综合征唇腭裂存在相关性。     

基因测序筛选前列腺癌患者PCA3(DD3)基因外显子多态性

目的 筛查前列腺癌患者PCA3基因外显子单核苷酸多态性位点,初步探讨PCA3基因多态性与前列腺癌的相关性.方法 采用基因测序法对41例前列腺癌(PCa)患者和40例良性前列腺增生(BPH)患者进行PCA3基因外显子SNP位点的筛选,对筛选到的sNP位点进行前列腺癌的相关性分析.结果 PcA3基因外显子1、外显子3、外显子4区域均未检测到基因多态性位点,PCA3基因外显子2区域存在1个SNP位点(A→C),基因型分别为AA型、AC型、CC型,该位点的基冈型频率和等位基因频率与前列腺癌存在相关性(P<0.05).结论 基因测序可有效筛选到PCA3基因外显子的SNP位点,PCA3基因外显子2基因多态性可能与前列腺癌发病风险有关.     

中国汉族NOS2基因多态性与自癜风发病相关性研究

目的:探讨NOS2基因-954 G→C位点多态性与白癜风发病的相关性.方法:采用聚合酶链反应和限制性片段长度多态性方法,对749例白癜风患者和763例健康人的NOS2基因-954 G→C位点基因型进行分析.结果:白癜风患者NOS2-954 G→C位点基因型的分布与正常对照组相比有显著性差异,联合基因型GC CC及C等位基因在白癜风患者中频率较高,与临床资料结合分析表明联合基因型GC CC在在发病年龄大于20岁组、活动期患者,皮节型白癜风及伴有自身免疫病和正常对照组之间无显著差异(P>0.05),但在发病年龄小于20岁组、稳定期患者、寻常型白癜风及无自身免疫病组的分布频率与正常对照组相比有显著性差异(P<0.05).结论:NOS2-954 G→c位点基因多态性与白癜风有明显的相关性.携带C等位基因可能会增加对白癜风的易感性.     

RET基因多态性与中国湖北地区汉族人群先天性巨结肠的相关性研究

目的建立中国汉族人群BET基因位于exon2（密码子45）、exon13（密码子769）、exon11（密码子691）和exon15（密码子904）的基因多态性的基因型和等位基因频率的分布背景，探讨其基因多态性与先天性巨结肠的关系。方法应用PCR-RFLP在中国湖北地区汉族人群中检测正常对照组（122例）及散发性先天性巨结肠组（HD组，94例）G45A（GCG→GCA）、T769G（CTT→CTG）、G691A（GGT→AGT）和C904G（TCC→TCG）的单核苷酸多态性（single nucleotide polymorphisms,SNPs）。结果G45A、T769G和G691A在对照组中均存在多态性，但未发现C904G存在基因多态性。均为CC型。G45A在对照组中的基因型频率分别为AA 0．17、AG 0．72和GG 0．11，突变型A和野生型G等位基因的频率为0．53和0．47；而G45A在HD组则分别为从0．61、AG 0．35和GG 0．04，突变型A和野生型G等位基因的频率为0．78和0．22。T769G在对照组中基因型频率分布分别为GG 0．30、GT 0．52和TT 0．18，G和T等位基因的频率为0．56和0．44；而T769G在HD组则分别为GG 0．49、GT 0．36和TT 0．15，突变型G和野生型T等位基因的频率为0．67和0．33。两组间的两个位点的基因型和等位基因的分布频率差异均有统计学意义（x^2=28．64，P〈0．001；x^2=5．27，P=0．022）。G691A在对照组中基因型频率分别为AA 0．05、AG 0．16和GG 0．79，突变型A和野生型G等位基因的频率为0．13和0．87；而在HD组则分别为AA 0．02、AG 0．14和GG 0．84，突变型A和野生型G等位基因的频率为0．09和0．91，两组间比较差异无统计学意义（x^2=1．232，P=0．267）。结论在中国湖北地区汉族人群中，RET密码子904可能不存在基因多态性，未发现G691A与先天性巨结肠存在相关性，而G45A和T769G的基因多态性可能与中国湖北地区汉族人群先天性巨结肠相关。     

Association of endothelin-beta receptor (EDNRB) gene variants in anorectal malformations

Animal models have demonstrated the role of genetic influences in anorectal malformations (ARM), although the pathogenetic mechanism remains uncertain. A body of collateral evidence points to possible connection with the endothelin-β receptor (EDNRB) gene and the endothelin system. This study investigates the EDNRB gene in patients with ARM.Resected surgical specimens of terminal colonic tissue were obtained from 14 children (6 males and 8 females) undergoing surgery for ARM correction with ethical permission. DNA samples were screened for mutations in EDNRB. Polymerase chain reaction amplification of 7 exons of EDNRB was followed by heteroduplex single-strand conformation polymorphism analysis. Heteroduplex single-strand conformation polymorphism variants were validated with automated sequencing techniques on polymerase chain reaction products showing conformational variants in acrylamide gel.All investigated patients with ARM showed mobility shift aberrations and polymorphisms in the EDNRB gene. These included one previously described polymorphism in exon 4 (831G/A) seen in association with Hirschsprung disease and 6 novel polymorphisms identified in exons 1 (178G/A), 2 (552C/T and 561C/T), and 3 (702C/T). No aberrant banding patterns were observed. The exon 1 (178 G/A) variation was identified in 2 (50%) of 4 low lesions compared with 1 (1%) of 84 control samples. The exon 3 (702C/T) single nucleotide polymorphism was present in 3 (60%) of 5 of the supralevator lesions being associated with exon 4 (831G/A). The patient with VATER associations including cardiac and limb anomalies had the 831G/A variation only.Analysis revealed statistically significant differences for the polymorphism 178G/A (P < .01, χ² with Yates correction = 8.24) compared to controls.Potential disease-related mutations were identified in South African patients with ARM, raising the question of its potential role in the pathogenesis of this condition.     

白介素-18基因多态性与结直肠癌易感性的关系

目的探讨白介素-18（m-18）基因单核苷酸多态性及其单倍型与结直肠癌易感性之间的关系。方法以170例结直肠癌患者和160名健康对照者为研究对象,应用聚合酶链反应一限制性片段长度多态性（PCR-RFLP）的方法对IL．18基因-137G／C、-607C／A单核苷酸多态性进行基因分型,同时用SHEsis软件分析IL-18基因的连锁不平衡及单倍型频率。结果IL-18基因-607C／A多态性在结直肠癌患者和健康人群中的分布差异无统计学意义（P〉0．05）．而IL-18基因-137G／C多态性在两组人群中的分布差异有统计学意义（P〈0．05）。等位基因频率的相对风险分析显示．C等位基因携带者患结直肠癌的风险是G等位基因的1．814倍（OR=1．814,95％CI：1．246～2．642）。联合基因型分析显示,IL-18基因-137G／C、-607C／A单核苷酸多态性存在着强烈的连锁不平衡（ID＇｜=0．945）,-137C／-607A单倍型频率在结直肠癌患者中显著高于健康人群（P〈0．05）。-137C／-607A单倍型携带者显著增加了结直肠癌的发病风险（OR=1．637,95％CI：1．100～2．437）。结论IL—18基因-137G／C多态性和-137C／-607A单倍型与结直肠癌的发病具有相关性．其中-137C等位基因可能是结直肠癌的遗传易感基因。     

HPC2/ELAC2 polymorphism associated with Japanese sporadic prostate cancer

BACKGROUND: HPC2/ELAC2 gene was identified by linkage analysis from familial prostate cancer (Pca) patients in USA. To determine the association of HPC2/ELAC2 gene with Japanese sporadic Pca, we performed a case-control study focused on two missense polymorphisms. METHODS: We genotyped the two polymorphic sites of Ser217Leu and Ala541Thr in sporadic Japanese Pca patients (n = 285) and matched controls (n = 233). Controls were unrelated Japanese outpatients who had no history of any cancer and normal PSA level (less than 4.0 ng/ml). Statistical analyses were performed by Mann-Whitney's U-test, Fisher's exact test, and logistic regression analysis. RESULTS: We observed a significantly higher frequency of the Thr allele at 541 polymorphic site in Pca patients (8.4%) compared to the control group (2.1%) (P = 0.0030, Odds Ratio (OR) = 4.02, 95% CI = 1.50-10.8). However, this SNP does not correlate with clinical stage, PSA level, Gleason score of biopsies or age at diagnosis. No association was identified at Ser217Leu polymorphic site. CONCLUSIONS: Our results indicate that Thr allele at 541 in HPC2/ELAC2 has strong significance in the predisposition of sporadic Pca in Japan. This polymorphism can be useful to predict the personal Pca risk, which lead the effective screening of Pca.     

维生素D受体基因FokⅠ多态性与良性前列腺增生合并组织学前列腺炎的关系

目的：研究维生素D受体（VDR）基因启动子FokⅠ多态性与良性前列腺增生（BPH）合并组织学前列腺炎的关系。方法：应用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）对79例BPH合并前列腺炎患者（炎症组）及81例单纯BPH患者（对照组）的外周血进行FokⅠ多态性检测,分析两组间基因型和等位基因的频率分布。结果：炎症组基因型分布FF：27%（21/79）,Ff：30%（24/79）,ff：43%（34/79）;对照组FF：33%（27/81）,Ff：36%（29/81）,ff：31%（25/81）,其中ff基因型分布在两组中差异有统计学意义（P〈0.05）。炎症组与对照组等位基因F分布频率分别为42%（142/338）和51%（159/312）,P〉0.05,f分别为58%（196/338）和49%（153/312）,P〈0.05。结论：VDR基因FokⅠ多态性与BPH中组织学前列腺炎发生有一定关系。     

DNA polymorphisms in exon 1 and promoter of the CDH1 gene and relevant risk of transitional cell carcinoma of the urinary bladder

OBJECTIVE

To investigate the association between DNA polymorphisms, including single‐nucleotide polymorphisms (SNPs) and insertion/deletion polymorphisms, in exon 1 and promoter of the CDH1 gene, and the risk of transitional cell carcinoma (TCC) of the urinary bladder (TCCB).

PATIENTS, SUBJECTS AND METHODS

This was a hospital‐based case‐control study of 180 patients with TCCB and 110 normal controls. Genomic DNA was extracted from blood samples of all participants and genotypes determined using polymerase chain reaction and DNA sequencing techniques. Haplotypes were analysed using appropriate software.

RESULTS

SNPs were detected at ?160A/C, ?73A/C and 178C/T; an inserted oligonucleotide of 5′‐CCGTGCCCCAGCC‐3′ was identified at 234 bp. The ?160A allele frequency in the case group was 0.67, statistically higher than in the control group (0.42; P < 0.001), and higher in invasive carcinoma (0.77) than in superficial carcinoma (0.60). For ?73C/A and 178C/T SNPs there was no difference among genotypes. The 234 repeat oligonucleotide insertion (2I) frequencies in cases was 0.27, statistically higher than in the control group (0.17; P = 0.01). The most common haplotype in controls was C‐A‐T‐I (28%), the frequency of which was higher than in the TCCB group (6%). The A‐A‐T‐2I was the only variation distribution carrying the ?160A allele and was at a statistically higher frequency in the TCCB group (37%, the most common haplotype in cases) than in the control group.

CONCLUSION

The ?160A, 234 2I allele and haplotype A‐A‐T‐2I were risk factors of TCCB. Haplotype C‐A‐T‐I might act as a protective factor for TCCB.     

脓毒症易感性与IRAK-M基因多态性的相关性

目的 探讨脓毒症易感性与IRAK-M基因多态性的关系.方法 选择脓毒症患者82例为实验组,118例健康人群为对照组.应用聚合酶链反应(PCR)-限制性片段长度多态性分析法(RFLP)分析IRAK-M+22148G＞A基因多态性.结果 脓毒症组IRAK-M+22148G＞A位点G/G基因型频率高于对照组(81.7%比28.8%),差异有统计学意义(P＜0.01),G等位基因频率高于对照组(84.1%比33.9%,P＜0.01),差异有统计学意义,脓毒症组肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6水平高于对照组[(843.00±97.34)ng/L比(287.00±79.12)ng/L;(741.00±65.61)ng/L比(194.00±58.47)ng/L],差异有统计学意义(P＜0.05);G/G基因型与脓毒症之间有明显相关(OR=11.03,95%CI:5.55～21.94).结论 IRAK-M+22148G/A基因多态性与脓毒症的易感性相关,G/G基因型者易患脓毒症.

Abstract：

Objective To determine the association between the genetic polymorphisms of IRAK-M and the susceptivity of sepsis. Methods Two candidate gene loci in + 22148G ＞ A patients with 82 sepsis infection and 118 heahhy controls were investigated. The polymorphisms were assessed by the polymerase chain reaction (PCR) and the restrict fragment length polymorphisms (RFLP). Results In sepsis group and control group, the frequency of G/G gene was 81.7% and 8. 8% ( P ＜0. 01 ) and that of G allele was 84.1% and 33.9% ( P ＜0. 01 ), respectively. The levels of tumor necrosis factor (TNF) -α and interleukin (IL) -6 in sepsis group were higher than in control group [ ( 843.00±97.34) vs (287.00±79.12) ng/L;(741.00±65.61) vs (194.00±58.47)ng/L,P＜0.05].The G/G genotype was associated with sepsis (OR=11.03,95% CI=5.55-21.94).Conclusion The genetic polymorphism of +22148 site of IRAK-M gene is associated with the susceptivity of sepsis.The G/G genotype is susceptive to sepsis.     

Association of hereditary prostate cancer gene polymorphic variants with sporadic aggressive prostate carcinoma

BACKGROUND: ELAC2, MSR1, and RNASEL are candidate genes for hereditary prostate carcinoma (HPC). While, studies have demonstrated that single nucleotide polymorphisms (SNPs) in these genes are associated with sporadic disease as well as HPC, these results are often not replicated in follow-up studies. Given that the majority of patients studied had localized disease and up to 50% of localized prostate cancer is clinically insignificant, the inability to replicate the initial findings may reflect that some subjects had indolent tumors. Herein, we examine patients with metastatic disease to determine if an association exists between HPC SNPs and unambiguously significant prostate cancer. METHODS: We examined polymorphisms within ELAC2 (S217L, A541T, E622V), MSR1 (P275A, R293X, aIVS5-59c), and RNASEL (E265X, R462Q, D541E) in 150 European-Americans with metastatic prostate cancer and 170 prostate cancer-free controls using pyrosequencing assays. RESULTS: Only ELAC2 217L (37% cases vs. 29% controls (P=0.034)) and RNASEL 541E (61% cases vs. 53% controls (P=0.045)) were over-represented. Analysis of genotypes revealed that presence of the leucine ELAC2 allele (OR 1.54: 95% CI=0.99-2.41, SS vs. SL, LL) and homozygosity for the glutamic acid RNASEL allele (OR 1.68: 95% CI=1.04-2.70, EE vs. DE, DD) were associated with increased risk. Patients with both genotypes were of particularly high-risk (OR 2.66: 95% CI=1.36-5.19). CONCLUSIONS: These results suggest that, in a European-American population, ELAC2 217L and RNASEL 541E are associated with metastatic sporadic disease. ELAC2 and RNASEL SNP analysis may prove useful in determining which patients are at risk for developing clinically significant prostate carcinoma.     

Interleukin-13 genetic polymorphisms in Singapore Chinese children correlate with long-term outcome of minimal-change disease.

BACKGROUND: Minimal-change nephrotic syndrome (MCNS) has been associated with atopy. As interleukin-13 (IL-13) has been implicated in the pathogenesis of MCNS, we postulated that IL-13 genetic polymorphisms could influence either susceptibility or clinical course of the disease. METHODS: Seventy-two Singapore Chinese children with MCNS and 78 normal controls were screened for single nucleotide polymorphisms (SNPs) in the IL-13 gene by direct sequencing. Allele and genotype frequencies of these SNPs were determined and their relationship with different clinical courses was analysed. RESULTS: Six SNPs were identified in the 5' promoter, exon 4 and 3' untranslated region (3'UTR). The three SNPs in the 3'UTR--4738 (G/A), 4793 (C/A) and 4926 (C/T)--were in tight linkage disequilibrium (Delta > or = 0.99). There was no difference in allele or genotype frequencies between MCNS children and normal controls. However, there was a significantly lower frequency of allele 4738G in those MCNS children who were still relapsing after 5 years of follow-up (G = 0.52), compared with those in complete remission (G = 0.72; P<0.05) and normal controls (G = 0.69; P<0.05). Haplotype analysis showed a significantly higher frequency of the GCC haplotype in controls and MCNS patients in complete remission (chi2 = 6.35; P<0.02), while the frequency of AAT haplotype was higher in those MCNS children still relapsing after 5 years of follow-up (chi2 = 5.38; P<0.02). Moreover, peripheral blood mononuclear cell IL-13 mRNA expression in patients with haplotype AAT was significantly higher than in those with haplotype GCC. CONCLUSIONS: These results suggest that genetic polymorphisms in the 3'UTR of the IL-13 gene correlate with long-term outcome of MCNS, rather than disease susceptibility, in Singapore Chinese children.     

RET 3'UTR polymorphisms and its protective role in Hirschsprung disease in Southeastern Chinese

BackgroundHirschsprung disease (HSCR) is a complex congenital disorder characterized by intestinal obstructions owing to the absence of the intestinal ganglion cells of the nerve plexuses in variable lengths of the digestive tract. Several RET polymorphisms and haplotypes have been described as underrepresented in HSCR patients with respect to controls. We thus sought to investigate whether polymorphisms in RET 3′UTR are associated with isolated HSCR in the Chinese population.MethodsPolymerase chain reaction amplification and direct sequencing were used to screen polymorphisms in RET 3′UTR in patients with sporadic HSCR and ethnically matched controls in Han Chinese populations. Association tests of RET 3′UTR variants and haplotypes with HSCR were performed.ResultsWe examined a total of 107 Chinese sporadic HSCR patients and 89 ethnically matched controls by sequencing the 3′UTR of the RET gene. Five single nucleotide polymorphisms (SNPs) and 2 monomorphic SNPs were identified. The genotype distributions and the allele frequencies of the 5 SNPs were significantly different between HSCR cases and controls and occurred more frequently in the control population. Haplotype analysis has shown a higher frequency of haplotypes comprising variant alleles in controls as compared with cases.ConclusionsThe significant deviations of the genotype distributions and the allele frequencies of these SNPs in the HSCR population compared with the control population demonstrate that these SNPs have a strong negative association with HSCR and could act as protective alleles.