线粒体827位点单核苷酸多态性与胆囊结石病易感性关系的研究

目的:研究线粒体单核苷酸多态性(SNPs)与胆囊结石病的关系,探讨导致胆囊结石病的可能易感因素。方法:对上海地区96个来自不同家系的胆囊结石病人和204名年龄<50岁且无胆囊结石的正常对照者进行线粒体DNACOX1基因、HVS1区和827位点序列检测;将测序结果与标准序列对比,以寻找存在的(SNPs),并比较各种SNP在两组之间的分布差异。结果:COX1基因6023G→A、6216T→C和6413T→C变异的分布在2组之间差异显著(P=0.036);线粒体第一高变区(HVS1)测序发现,16136C鄄16189C鄄16217C变异在2组之间差异显著(P=0.022);827位点序列检测发现827A→G在2组之间差异显著(P=0.000364)。结论:中国南方人群中,线粒体B4b单倍群个体(827A→G)易感胆囊结石病。     

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。     

X射线损伤修复交叉互补基因1的单核苷酸多态性与散发性结直肠癌易感性相关

目的 检测单核苷酸多态性（SNP）位点Arg399Gln在散发性结直肠癌患者和非癌对照组中的分布情况，分析其与散发性结直肠癌及其临床病理特征的相关性。方法 从178例肿瘤组织和非癌对照组的180例血样中提取DNA，采用Taqman探针技术检测Arg399Gln多态性表型，并用统计软件计算各基因型的比值比（OR）和95％可信区间（95％CI）。结果 肿瘤组与对照组就XRCC1Arg399Gln多态性的基因表型差异有统计学意义（P〈0．05）；年龄不超过60岁的患者和超过60岁的患者在该位点的基因型差异有统计学意义（P〈0．05）；以399Arg／Arg基因型为参照，在年龄超过50岁的人群中（OR=0．64，95％C10．50～0．83，P〈0．05）和男性人群中（OR=0．64，95％C10．51～0．79，P〈0．05）携带至少一个Gin等位基因可致罹患散发性结直肠癌的风险显著降低；XRCC1399SNP与患者性别及散发性结直肠癌的发生部位、Dukes分期、浸润深度、淋巴结转移以及病理分型均无显著相关性（P均〉0．05）。结论 XRCC1399SNP可能通过改变DNA的损伤修复功能，成为散发性结直肠癌的易感因素。     

TGF-β3基因SfaNⅠ多态性与非综合征性唇腭裂的遗传易感性

目的探讨TGF-β3基因SfaNⅠ多态性与中国人群发生非综合征性唇腭裂（NSCL／P）的关系。方法选取48个核心家庭的48例NSCL／P患儿为实验组；选取48例正常儿童为对照组。应用聚合酶链式反应——限制性片段长度多态性方法，进行TGF-β3基因SfaNⅠ多态性检测。对48例患儿行以其父母及48例正常儿童为对照的研究方法。计算48例患儿与其父母的传递失衡指数（TDT）和基于单体型的单体型相对危险度（HHRR）。计算48例患儿与48例正常儿童的基因型及基因频数。结果48个核心家庭中，有30对杂合子父母，其TDT（Х^2）=0．024,P〉0．05；HHRR（Х^2）=0．035，P=0．852〉0．05；OR=0．933，95%CI=0．448-1．940。48例患儿和48例正常儿童的基因型及等位基因频数。Х^2=3．43,P〉0．05。结论TGF-β3基因SfaNⅠ位点多态性可能不是中国人群发生NSCL／P的遗传易感因素。     

钙敏感受体基因第7外显子单核苷酸多态性与特发性高钙尿症的关系

目的了解钙敏感受体（CaSR）基因单核苷酸多态性与特发性高钙尿（IH）症的关系，探讨特发性高钙尿发病的分子机制。方法提取76例湖北地区汉族特发性高钙尿患者及126例健康对照者外周血标本中基因组DNA，应用聚合酶链反应（PER）结合DNA测序方法检测并分析了CaSR基因的第7外显子3个簇集的多态性位点单核苷酸多态性分布。结果特发性高钙尿病例和对照组CaSR基因的第7外显子第986、990多态性位点等位基因频率分布均符合Hardy-Wein-berg定律，其基因型分布频率在特发性高钙尿患者和正常对照者中差异无统计学意义（P〉0．05），第1011位未见有多态改变。但特发性高钙尿组组内CaSR 990位GG纯合子和RG杂合子个体的24h尿钙排泄量较RR纯合子明显增高，差异有统计学意义（P〈0．05）。结论CaSR基因不是特发性高钙尿的易感主基因，但第7外显子990位A／G单核苷酸多态性能影响尿钙排泄，可能是特发性高钙尿中调节钙排泄的遗传成分之一。     

胸腺肽α1对重症肺部感染患者T淋巴细胞亚群比例的影响

目的 探讨胸腺肽钒对重症肺部感染患者T淋巴细胞亚群比例的影响。方法 20例ICU重症肺部感染患者，年龄58—83岁，体重50—68kg。随机分为对照组（A组）和胸腺肽α1组（B组），每组10例。B组在接受A组治疗方案的基础上加用胸腺肽α1。在治疗前1d和治疗开始后1、2、3、4、5、6、7d进行血常规检测，采用间接免疫荧光法测定外周血T淋巴细胞亚群CD3^＋、CD4^＋、CD8^＋比例，并观察患者临床症状、体征及胸部X片变化，进行疗效评价。结果 治疗前2组白细胞计数（WBC）、中性粒细胞比例均高于正常值，CD3^＋、CD4^＋亚群比例均低于正常值；治疗开始后4—7d后，B组WBC、中性粒细胞比例低于A组（P〈0．05），CD3^＋、CD4^＋；亚群比例及CD4^＋／CD8^＋比值高于A组（P〈0．01）；A组、B组感染控制总有效率分别为70％、90％，1月内病死率分别为40％、30％，组间比较差异均无统计学意义（P〉0．05）。结论 胸腺肽α1可增加重症肺部感染患者CD3^＋、CD4^＋淋巴细胞亚群比例及CD4^＋／CD8^＋比值，有利于重症感染的控制。     

胆囊结石病家系的基因多态性研究

目的 从胆囊结石病多发家系角度来探讨胆石症发病的分子基础并研究部分胆石病易感基因在胆石病家系成员中的分布及与胆石病的关系。方法 收集调查上海地区93个胆石病家系，通过胆囊B超检查证实每个家系至少有2名胆石病患，对333名家系成员（其中患239人）进行临床调查并检测血脂水平，应用PCR－RFLP（PCR－限制性多形性碎片长度）法来检测胆石病易感基因载脂蛋白B（Apo B)基因Xbal和载脂蛋白E（Apo E)基因Hha I的多态性位点基因型，分析各基因型和等位基因在家系成员中的分布情况。结果 （1）Apo B基因Xba I多态性X^ /-基因型频率在胆石组为5．9％，非胆石组为10．6％，分布无显性差异。不同的Apo B基因型，其血液生化指标无显性差异。（2）Apo E基因多态性各等位基因ε2、ε3和ε4的分布频率在胆石组分别为：6．9％、81．4％和11．7％，在非胆石组分别为：9．0％、81．4％和9．6％，分布无显性差异。年龄段为≤40岁的家系成员中，Apo E4/x(Apo E3/4,Apo E4/4)基因型在胆石组的分布频率（20．6％）显高于非胆石组（0％）（P＝0．04）。不同的Apo E基因型对血脂水平有着不同的影响，总体上看，E2／x(Apo E2/2,Apo E2/3)基因型的血清TG和HDLC显升高，LDLC显降低（P＜0．05）；而E4／x基因型的TC、LDLC、Apo B以及Apo E均显升高，HDLC、Apo A1显降低（P＜0．05）。结论 ε4等位基因可能是胆石病的易感基因，Apo B基因X^ 等位基因和胆石病的关系有待进一步确定。     

南方汉族等候肾移植终末期肾功能衰竭患者HLA基因多态性分析

目的对我国南方地区3911例等候肾脏移植的患者进行HLA-A，B，DRB1基因表达的回顾性研究，以探讨在因肾脏疾病导致患者最终并发终末期肾功能衰竭（EsRD）进程中的HLA免疫遗传易感性及其相对风险作用。方法采用聚合酶链反应-序列特异性引物扩增（PcR-SSP）技术进行HLA-A，B，DR基因分型，应用SPPS13．0软件包统计分析ESRD患者中HLA抗原频率、基因频率、HLA—A，B，DR三个位点的单倍型频率（HF）、连锁不平衡参数、相对危险度（RR）及优势比（OR）。结果ESRD患者中表达出HLA-A抗原19个，HLA-B抗原40个，HLA-DR抗原14个；其中呈现抗原频率显著增高（Pc〈O．0001，Pc值即P值乘以所检测的某一位点的抗原数）的是HLA-B75（RR=1．222，OR=1．479）、DR4（RR=1．146，OR=1．294），DR17（RR=1．541，OR=2．639）；呈现出抗原频率显著降低（Pc〈0．0001）的是HLA-DR8（RR=0．812，DR=0．697）、DR9（RR=0．878，OR=0．793）；ESRD患者中具有显著连锁不平衡单倍型（HF〉0．5％）10条，分别为A1-B37．DR10，A2-B7-DR17，A29-B7-DR10，A30-B13-DR7，A33-B13-DR17，A33-B44-DR17，A33-B46-DR17，A33-B58-DR17，A33-B60-DR17和A33-B75-DR17，其中A33-B75-DR17、A33-B58-DR17频率高达7．93％和11．74％。结论研究发现HLA-B75、DR4和DR17可能对南方地区肾脏疾病患者最终并发ESRD具有独立易感关联，而表达HLA-DR8、DR9的肾脏病患者将可能不易并发ESRD；单倍型A33-B75-DR17高频率出现说明HLA-B75，DR17不仅具有独立易感作用还可能对肾脏病患者最终并发ESRD具有集合易感作用。这个发现对于等候肾脏移植患者选择合适供体以提高移植后患者生存时间和远期移植效果具有临床指导意义。     

Ⅲ型前列腺炎辅助性T细胞亚群的分化

目的 了解Ⅲ型前列腺炎前列腺液中CD4^＋T辅助性T细胞（Th细胞）亚群的分化情况。方法 按照美国国立卫生院（NIH）分类方法将病例分成ⅢA型／组（47例）、ⅢB型／组（29例），另设健康对照组（16例）。采用双抗体夹心酶联免疫法检测前列腺液（EPS）中Th；类细胞因子（IFN-γ）、Th2类细胞因子（IL-4）水平以及Th1／Th2比值（IFN-γ／IL-4）。结果 和对照组比较，ⅢA组、ⅢB组IFN-γ水平明显上调（P〈0．05），ⅢA组较ⅢB组升高更明显（P〈0．05）；和对照组比较，ⅢA组IL-4水平无明显变化（P〉0．05），ⅢB组IL-4水平上调（P〈0．05）：和对照组比较，ⅢA组IFN-γ／IL-4明显升高（P〈0．05），ⅢB组IFN-γ／IL-4无明显改变（P〉0．05）。结论 ⅢA型前列腺炎Th；细胞分化占优势，Th1／Th2平衡向Th1漂移，以细胞免疫反应为主；Th细胞分化也参与了ⅢB型前列腺炎的发病，但Th1／Th2处于相对平衡状态。     

瘢痕疙瘩发病风险与Fas基因-670位点多态性

目的：研究Fas基因-670位点多态性与瘢痕疙瘩发病风险的关系。方法：采用聚合酶链反应-反向点杂交、DNA直接测序方法，检测了75例瘢痕疙瘩患者与120名正常对照的Fas基因-670多态性位点的基因型。结果：瘢痕疙瘩患者的A等位基因频率明显高于正常对照组（x^2=4．408，P=0．036）。瘢痕疙瘩患者的A／G、G／G基因型频率与正常对照组相比差异无统计学意义（χ^2值分别为1．051和1．134；P值分别为0．305和0．287），而瘢痕疙瘩患者的A／A基因型频率明显高于对照组（χ^2=5．207，P=0．022）。提示A／A基因型者患瘢痕疙瘩的风险性明显高于A／G、G／G基因型者（OR=2．122，95％CI：1．105～4．077）。结论：Fas基因-670多态性位点的基因型检测可能对判断瘢痕疙瘩高危个体具有指导意义。     

Women with mitochondrial haplogroup N9a are protected against metabolic syndrome

To identify mitochondrial haplogroups that confer resistance against or susceptibility to metabolic syndrome, we performed a large-scale association study on 1,337 unrelated Japanese individuals, including 871 subjects with metabolic syndrome and 466 control subjects. Metabolic syndrome was diagnosed according to modified National Cholesterol Education Program Adult Treatment Panel III guidelines, using the cutoff point for obesity as a BMI of >/=25 kg/m(2) instead of waist circumference. The genotypes for 25 polymorphisms in the coding region of the mitochondrial genome were determined, and the haplotypes were classified into 10 major haplogroups, i.e., F, B, A, N9a, M7a, M7b, G1, G2, D5, and D4. Multivariate logistic regression analysis revealed that the haplogroup N9a was significantly associated with resistance against metabolic syndrome in women with an odds ratio (OR) of 0.21 (95% CI 0.07-0.58, P = 0.0042). Women with haplogroups G1 and D5 tended to be resistant against metabolic syndrome with an OR of 0.22 (0.06-0.68, P = 0.0129) for G1 and with an OR of 0.32 (0.10-0.96, P = 0.0469) for D5, respectively. These results indicate that mitochondrial haplogroup N9a may be a protective factor against metabolic syndrome in Japanese women.     

Prostate cancer incidence varies among males from different Y-chromosome lineages

The incidence rate of prostate cancer in African-American males is two times higher than Caucasian men and ten times higher than Japanese men. The geographical specificity of Y haplogroups implies that males from different ethnic groups undoubtedly have various Y lineages with different Y-chromosomal characteristics that may affect their susceptibility or resistance to such a male-specific cancer. To confirm this hypothesis we studied the Y-chromosomal haplogroups of 92 Japanese prostate cancer patients comparing them with randomly selected 109 unrelated healthy Japanese male controls who were confirmed to be residents of the same geographical area. Males could be classified using three binary Y-chromosome markers (sex-determining region Y (SRY), YAP, 47z) into four haplogroups DE, O2b(*), O2b1, and untagged group. Our results confirmed that prostate cancer incidence varies among males from different Y-chromosome lineages. Males from DE and the untagged haplogroups are at a significantly higher risk to develop prostate cancer than O2b(*) and O2b1 haplogroups (P=0.01), odds ratio 2.17 and 95% confidence interval (1.16-4.07). Males from haplogroup DE are over-represented in the patient group showing a percentage of 41.3%. The underlying possible causes of susceptibility variations of different Y lineages for such a male-specific cancer tumorigenesis are discussed. These findings explain the lower incidence of prostate cancer in Japanese and other South East Asian males than other populations. To our knowledge, this is the first reliable study examining the association between prostate cancer and Y-chromosomal haplogroups, comparing prostate cancer patients with carefully selected matched controls.     

IgA肾病患者C1GALT1C1基因的体细胞突变筛查

目的 探讨IgA肾病（IgAN）患者β1,3半乳糖转移酶的分子伴侣Cosme编码基因C1GALT1C1基因体细胞突变情况。方法 27例IgA肾病患者及19例正常健康对照作为研究对象。提取研究对象外周血基因组DNA,扩增C1GALT1C1基因的编码区,采用PCR产物直接测序的方法进行突变筛查。然后,分离其中15例IgA肾病患者及7例健康男性对照的外周血B淋巴细胞,提取DNA。对C1GALT1C1基因编码区进行扩增,PCR产物进行克隆,各挑选平均8～10个克隆进行体细胞突变筛查。结果 46例个体全血基因组DNA的PCR扩增产物测序发现,2例患者及1例健康对照存在外显子T393A变异,次等位基因频率（MAF）为6．9%[SNP数据库（dbSNP）报告为9．5%]。B淋巴细胞DNA序列分析显示,在22例个体（15例IgA肾病患者,7例健康对照）送检的总共202个克隆中,未发现新的突变和多态性位点。结论 C1GALT1C1基因编码区T393A多态位点在本研究人群中为唯一发现的多态性位点,其次等位基因频率（MAF）较既往报道略低。本研究尚未发现IgA肾病患者B淋巴细胞存在体细胞突变。     

胆石症胆囊切除术与大肠癌关系探讨

目的探讨胆石症胆囊切除术与大肠癌之间的发病关系。方法分析近１０年来经病理确诊的２３８例大肠癌与本院年龄性别匹配的非大肠癌３９５例进行对照研究。结果胆石症和胆囊切除术伴大肠癌与对照组比较,其相对危险性（ＯＲ）为２９５,９５％可信限１８９～４５９,χ２＝２２３１,Ｐ＜００１。胆石症与胆囊切除术例数相比为４０ｖｓ．１３（Ｐ＜００１）。６０岁以上行胆囊切除术者占６９２％（Ｐ＜００１）。女性胆石症伴结肠癌和直肠癌与男性相比,ＯＲ分别为１３７和１９９;与左结肠癌相比,发生右结肠癌的相对危险性是２１,但差异均无显著性意义。结论主要是由于胆石症,而不是胆囊切除术,增加了发生大肠癌的危险性。另外,６０岁以上的胆囊切除术患者,大肠癌发病的相对危险性可能增高     

Mitochondrial DNA haplogroup associated with sperm motility in the Han population

In this study, we aimed to determine whether the main mitochondrial DNA （mtDNA） haplogroups of the Han people have an impact on spermatozoa motility, We recruited 312 men who were consecutively admitted to two affiliated hospitals of College of Medicine, Zhejiang University from May 2011 to April 2012 as part of fertility investigations. Semen and whole blood samples were collected from the men. We determined the mtDNA haplogroups by analysing the sequences of mtDNA hypervariable segment I and testing diagnostic polymorphisms in the mtDNA coding region with DNA probes, No significant differences were found in the clinical characteristics of the mtDNA haplogroup R and non-R （P〉0.05）. Our results suggest that mtDNA haplogroup R is a strong independent predictor of sperm motility in the Han population, conferring a 2.97-fold （95% confidence interval： 1.74-4.48, P〈0.001） decreased chance of asthenozoospermia compared with those without haplogroup R.     

Association of MSY haplotype background with nonobstructive azoospermia is AZF-dependent: A case-control study

Identifying causal genes of spermatogenic failure on the male-specific region of Y chromosome (MSY) has been a challenging process. Due to the nonrecombining nature of MSY, haplotype-based approaches have recently been shown to be promising in identifying associated MSY haplogroups. We conducted an MSY analysis of nonobstructive azoospermia (NOA) patients in a case–control setting (N = 278 and 105 respectively) to identify modal haplogroups strongly associated with NOA. Patients with AZF deletions (AZF+) and no AZF deletions (AZF-) were compared with the control group. Given the larger sample set of AZF- NOA patients, we further investigated the association based on histopathological severity, namely Sertoli cell-only syndrome and maturation arrest subtypes. We observed no significant enrichment of MSY haplogroups in AZF- azoospermic patients (or its subtypes). However, we observed a strongly significant association between haplogroup J2a* and AZF+ patients (FDR-corrected p = .0056; OR = 7.02, 95%CI 1.89 to 39.20), a haplogroup which also showed significant enrichment for AZFa/b deletions (p = 4x10^-4). We conclude that unlike AZF+ patients, AZF- NOA are less likely to have an MSY causative factor with large effect size, thus indicating that the aetiology of AZF- NOA, and to some extent AZFc NOA, is more likely to be based on non-MSY factors.     

Gallbladder wall inflammatory cells in pediatric patients with biliary dyskinesia and cholelithiasis: a pilot study

Background/Purpose

Inflammation has been implicated in functional gastrointestinal disorders, including functional dyspepsia and irritable bowel syndrome. This study was undertaken to evaluate gallbladder wall inflammatory cells in children with abdominal pain related to gallstones and biliary dyskinesia to determine the candidate cell types that may be contributing to the pathophysiology of these entities.

Methods

Gallbladder specimens from 20 patients with cholelithiasis, 20 biliary patients with dyskinesia, and 12 autopsy controls were evaluated in a blinded fashion. Eosinophil, tryptase-positive, and CD3+ cell densities were determined for the lamina propria and muscularis mucosa layers and compared between groups.

Results

Patients with biliary dyskinesia and cholelithiasis had a 9- to 12-fold increase in mean and peak mast cell densities, respectively, in both layers as compared with controls. Peak (13.7 vs 8.4) and mean (9.2 vs 5.2) CD3+ cell densities were increased in the muscularis mucosae of cholelithiasis specimens as compared with biliary dyskinesia specimens.

Conclusion

Gallbladder wall inflammatory cell densities, particularly mast cells, differ between children with cholelithiasis, children with biliary dyskinesia, and controls. Future studies are warranted to define the roles for specific inflammatory cell types.     

Genetic polymorphism of glutathione S-transferase T1 gene and susceptibility to idiopathic azoospermia or oligospermia in northwestern China

Aim： To investigate the association of glutathione S-transferase T1 （GSTT1） gene polymorphism in patients with idiopathic azoospermia or oligospermia in the northwestern China population. Methods： In the case-control study, GSTT1 genotypes were identified by multiplex polymerase chain reaction （PCR） with peripheral blood DNA samples from 78 patients with idiopathic azoospermia, 103 patients with idiopathic oligospermia and 156 age-matched controls with normal sperm concentration and motility, according to the criteria adapted from World Health Organization guidelines. All of the patients and controls were from northwestern China. Results： There is a significant association between GSTT1 null genotype with idiopathic azoospermia risk （odds ratio [OR]： 2.36, 95% confidence interval [CI]： 1.33-4.20, P = 0.003） or idiopathic oligospermia risk （OR： 2.00, 95% CI： 1.17-3.27, P = 0.010）. Conclusion： GSTT1 null genotype is a predisposing risk factor for sporadic idiopathic azoospermia or oligospermia in northwestern China. （Asian J Androl 2008 Mar; 10： 266-270）     

North American white mitochondrial haplogroups in prostate and renal cancer

PURPOSE: While the mitochondrion is known to be a key mediator of apoptosis, there has been little inquiry into the inheritance pattern of mitochondria in patients with cancer. We compared the mtDNA haplotype in patients with prostate and renal cancer to that in controls to determine if there is an association between mitochondrial genotype and cancer. MATERIALS AND METHODS: Haplotyping was performed using polymerase chain reaction/digest identification of key polymorphic sites in the mitochondrial genome. A total of 121 and 221 white men with renal and prostate cancer, respectively, were identified following pathological confirmation of cancer, while 246 white controls were selected randomly from a bank of cadaveric organ donor DNA. Statistical analysis was performed and ORs were calculated. RESULTS: Mitochondrial haplogroup U was a highly significant risk factor for prostate and renal cancer vs controls (16.74% and 20.66% vs 9.35%, Fisher's exact test p = 0.019 and 0.005, respectively). The association remained statistically significant in renal cancer even after Bonferroni adjustment for multiple comparisons. Haplogroup U carried an OR of 1.95 for prostate cancer and an OR of 2.52 for renal cancer. CONCLUSIONS: The inheritance of mitochondrial haplogroup U is associated with an approximately 2-fold increased risk of prostate cancer and 2.5-fold increased risk of renal cancer in white North American individuals. Therefore, individuals with this mitochondrial haplotype are in a high risk group. Because mitochondrial haplogroup U is found in 9.35% of the white United States population, there are more than 20 million individuals in this high risk group.     

醛固酮合酶和11-β羟化酶基因多态性与原发性醛固酮增多症发病风险的相关性研究

目的 研究醛固酮合酶基因(CYP11B2)和11-β羟化酶基因(CYP11B1)多态性与原发性醛同酮增多症(PA)发病风险之间的相关性.方法 对醛固酮瘤(APA)和特发性醛崮酮增多症(IHA)患者(APA 134例,IHA 45例)及正常人群(118名)中CYP11B2和CYP1181基因的5个多态性位点进行检测.其中,intron 2采用2个独立的PCR反应,其余位点均采用Taqman探针法.采用Haploview 4.0、SNPassoc 1.5-3和Haplo.stats 1.3.8软件分析CYPllB2和CYP1181基因多态性与PA的关系.结果 所选位点均获成功检测,APA和IHA组中rs6410位点的A等位基因频数显著高于对照组(P=1.09×10-5,P=0.015).与对照组相比,APA组中rs6410位点AA基因型和AG基因型比例增高(P=2.19×10-4),而IHA组中rs6410位点AA基因型和AG基因型仅在年龄、性别和体质量指数校对后比例增高(OR=4.06,95%CJ 1.31～12.66;OR=2.41,95%CI 1.02～5.72).APA组中发现1个易感单体型AAAWT(OR=1.44,95%CI 1.19～1.76),IHA组中发现3个易感单体型AAAWT、AGGWT和AGAWC(OR=1.55,95%CI 1.23～1.96;OR=1.49,95%CI 1.17～1.89;OR:1.40,95%CI 1.04～1.88).同时在APA组中发现1个保护性单体型GGAWT(OR:0.73,95%CI 0.55～0.97).结论 CYP11B2和CYP11B1基因多态性与APA和IHA的发病显著相关.