Novel mitochondrial 16S rRNA mutation, 3200T→C, associated with adult-onset type 2 diabetes

Objective To investigate the role of a potential diabetes-related mitochondrial region, which includes two previously reported mutations, 3243A→G and 3316G→A, in Chinese patients with adult-onset type 2 diabetes. Methods A total of 277 patients and 241 normal subjects were recruited for the study.Mitochondrial nt 3116-3353, which spans the 16S rRNA, tRNA(leu(UUR)) and the NADH dehydrogenase 1 gene, were detected using polymerase chain reaction (PCR),direct DNA sequencing, PCR-restriction fragment length polymorphism and allele-specific PCR.Variants were analyzed by two-tailed Fisher exact test. The function of the variants in 16S rRNA were predicted for minimal free energy secondary structures by RNA folding software mfold version 3. Results Four homoplasmic nucleotide substitutions were observed, 3200T→C, 3206C→T, 3290T→C and 3316G→A.Only the 3200T→C mutation is present in the diabetic population and absent in the control population.No statistically significant associations were found between the other three variants and type 2 diabetes.The 3200T→C and 3206C→T nucleotide substitutions located in 16S rRNA are novel variants.The 3200T→C caused a great alteration in the minimal free energy secondary structure model while the 3206C→T altered normal 16S rRNA structure little. Conclusions The results suggest that the 3200T→C mutation is linked to the development of type 2 diabetes, but that the other observed mutations are neutral.In contrast to the Japanese studies, the 3316G→A does not appear to be related to type 2 diabetes.     

线粒体DNA3160-3755区域基因突变与2型糖尿病的关系

目的研究线粒体DNA3160-3755区域基因在延边地区2型糖尿病（T2DM）患者中的突变情况,探讨该区域线粒体基因突变与2型糖尿病的关系。方法应用聚合酶链反应-限制性片段长度多态性（polymorphismchainreaction-restrictionfragmentlengthpolymorphism,PCR-RFLP）技术和直接测序法对延边地区人群108例正常健康体检者、328例T2DM患者（其中2例合并耳聋）,进行线粒体DNA3160-3755区域基因突变筛查。结果线粒体DNA3316G-A在糖尿病组和正常对照组中的突变率分别为3．7％和3．8％。两组间差异无统计学意义（P〉0．05）;3394T→C在糖尿病组和正常对照组中的突变率分别为7．3％和1．9％,两组间差异有统计学意义（P〈0．05）;在糖尿病组及正常对照组中均未检测到线粒体DNA3243A→G、3593T→C和3714A→G突变。结论线粒体DNA3316G→A突变与延边地区T2DM的发生无关;线粒体DNA3,394T→C突变与延边地区T2DM的发生有关;线粒体DNA3423A→G,3593T→C,3714A→G突变在延边地区T2DM中的发生率为0,提示上述位点基因突变率极低。     

Mitochondrial gene mutations and type 2 diabetes in Chinese families

Background Numerous mitochondrial DNA mutations are significantly correlated with development of diabetes. This study investigated mitochondrial gene, point mutations in patients with type 2 diabetes and their families.
Methods Unrelated patients with type 2 diabetes （n=826） were randomly recruited; unrelated and nondiabetic subjects （n=637） served as controls. The clinical and biochemical data of the participants were collected. Total genome was extracted from peripheral leucocytes. Polymerase chain reaction, restriction fragment length poiymorphism （PCR-RFLP） and cloning techniques were used to screen mitochondrial genes including np3316, np3394 and np3426 in the ND1 region and np3243 in the tRNA^Leu（UUR）.
Results In 39 diabetics with one or more mitochondrial gene point mutations, the prevalence （4.7%, 39/826） of mtDNA mutations was higher than that （0.7%, 5/637） in the controls. The identical mutation was found in 23 of 43 tested members from three pedigrees. Affected family members presented with variable clinical features ranging from normal glucose tolerance to impaired glucose tolerance （IGT） （n=2）, impaired fasting glucose （IFG） （n=1） to type 2 diabetes （n=13） with 3 family members suffering from hearing loss.
Conclusions Type 2 diabetes in China is associated with several mitochondrial gene mutations. Aged patients with diabetic family history had a higher prevalence of mutation and various clinical pictures. Mitochondrial gene mutation might be one of the genetic factors contributing to diabetic familial clustering.     

线粒体DNA3316、3394等4个突变位点与2型糖尿病的关系研究

目的:探讨DNA tRNA Leu(UUR)基因及ND-1基因3316 G/A、3394 T/C等4个突变位点与2型糖尿病的关系。方法:对236例海南地区2型糖尿病患者和252例健康对照者进行空腹血糖测定并采用聚合酶链式反应—限制性核酸内切酶片段长度多态性(PCR-RFLP)的分析方法进行mtDNA的3243、3316、3394、和3593共4个位点进行突变筛选,并采用DNA测序方法确证。结果:实验组空腹血糖(9.37±3.01)mmol/L与健康对照组(4.96±0.76)mmol/L差异有统计学意义(P<0.05);实验组检出3316(G→A)突变8例,3394(T→C)突变3例;健康对照组未发现上述突变;突变检测结果与测序一致。两组间3316(G→A)突变率差异有统计学意义(P<0.05)。结论:线粒体DNAtRNALeu(UUR)基因及ND-1基因3316、3394位点的基因突变,尤其是3316位点(G→A)突变可能与某些核基因或环境因素协同促进了2型糖尿病的发生。     

Prevalence and clinical characteristics of mitochondrial tRNA leu(UUR) mt 3243 A→G and ND-1 gene mt 3316 G→A mutations in Chinese patients with type 2 diabetes

Objective To assess the prevalence of mitochondrial tRNA leu((UUR)) gene mt 3243 A→G mutation and ND-1 gene mt 3316 G→A mutation in Chinese type 2 diabetes. Methods 716 randomly selected, unrelated patients with type 2 diabetes were screened for the mutation with a PCR-RFLP technique.Results Three individuals with mitochondrial tRNA leu((UUR)) gene mt 3243 A→G mutat ion were identified, representing approximately 0.4% of the type 2 patients scr eened.Further screening of first-degree relatives of these 3 patients identi fied another 4 affected carriers.In comparison with type 2 diabetic patients without the mutation, these 7 carriers of the mt3243 mutation had: 1) an earlier diagnosis age of diabetes (38.0±10.1 year vs 53.4±10.0 year, P&lt;0.001 ); 2) lower Body Mass Index (BMI) (19.5±2.0 kg/m(2) vs 24.9±10.9 kg/m(2) , P&lt;0.0001); and 3) lower post-challenge insulin levels (Area under the cu rve of insulin levels during the Oral Glucose Tolerance Test (OGTT), 2946±1647 .2 μIU·ml［-1］ vs 7469±6647.7 μIU·ml［-1］, P&lt;0.01).ND- 1 gene mt 3316 G→A mutation was found in 16 patients with type 2 diabetes (2.2 %) and 5 out 181 controls (2.7%) with normal glucose tolerance.Therefore, th e frequency of the mutation was not different in patients and controls.Moreov er, clinical characteristics such as age of onset of diabetes, BMI, and insulin levels were not different between diabetic patients with the mt 3316 mutation an d those without it.Conclusions In this large cohort of Chinese Type 2 diabetes, the prevalence of mitochondrial tRNA leu((UUR)) gene mt 3243 A→G mutation was 0.4%, and the ND-1 gene mt 3316 G→A mutation is a polymorphism unrelated to diabetes.     

糖尿病线粒体ND1基因3316 G→A突变的功能研究

目的 探讨线粒体ND1基因3316 G→A突变对线粒体生物学功能的影响及其在糖尿病发病中的作用.方法 利用真核表达载体pcDNA3.1B和大肠杆菌DH5α构建野生型和线粒体DNA的ND1基因3316 G→A突变型重组子pcDNA3.1B-ND1;设计特异性siRNA序列干扰Hela细胞内源性线粒体DNA表达,使其内源性ND1基因沉默;经脂质体转入野生型和突变型重组子pcDNA3.1B-ND1,使其在Hela细胞内表达.通过RT-PCR、十二烷基硫酸钠-聚丙烯酰胺凝胶电泳和荧光显微镜,从mRNA水平→蛋白质水平→线粒体膜电势位检测干扰效果,以筛选有效干扰siRNA序列.结果 线粒体ND11和线粒体ND12 siRNA序列均具有一定的干扰效果,后者效果明显优于前者;转入3316 G→A突变型重组子pcDNA3.1B-ND1的Hela细胞表达的线粒体蛋白低于野生型.结论 线粒体DNA的ND1基因正常表达对维持正常的呼吸链功能和细胞增殖至关重要,携有3316 G→A突变基因的糖尿病的发病与线粒体蛋白表达下降有关.     

线粒体DNA 3243、3316、3394位点突变与精神分裂症相关分析

目的分析线粒体tRNALeu(UUR)基因3243位点及ND1基因3316、3394位点突变对精神分裂症(SZ)发病的影响。方法采用PCR扩增、限制性内切酶消化、琼脂糖凝胶电泳分型检测、DNA测序等方法,对随机抽取的无亲缘关系的250例患者(SZ组)和292例对照组的外周血mtDNA进行3243、3316和3394位点的突变检测。结果在SZ组中发现8例3316G/A突变,对照组中3例,两组相比差异无统计学意义(P=0.138)。在SZ组中发现15例3394T/C突变,对照组中有4例,两组相比差异有统计学意义(P=0.007)。在精神分裂症患者组和对照组中均未发现3243A/G突变。结论 mtDNA3394T/C突变可能与SZ发生有一定关系,mtDNA 3243A/G、3316G/A突变可能与SZ发生无关。     

浙江汉族人群线粒体DNA ND1基因G3316A突变与2型糖尿病

目的：研究与日本人2型糖尿病（type 2 diabetes mellitus,T2DM）相关的线粒体DNA（mitochondria DNA,mtDNA）ND1基因G3316A突变在浙江汉族T2DM人群中的发生率及其临床意义。方法：采用PCR产物直接测序法对浙江籍汉族人群中无血缘关系的315名T2DM患者及158名正常对照的外周血mtDNA进行检测,并用DNASTAR和Antheprot 5.0软件分析突变位点。结果：在T2DM患者中检测到6例（占1.90%）G3316A突变,对照组中发现3例（占1.90%）突变,突变发生率在两组间差异无显著性（P＆gt;0.05）。携带G3316A位点突变的T2DM组与无该突变的T2DM组之间的临床特点（发病年龄、体重指数和血糖水平等）比较差异亦无显著性。蛋白二级结构中α-螺旋、β-折叠、β-转角和不规则卷曲的构成比没有发生改变。结论：线粒体DNA ND1基因G3316A突变可能与浙江汉族人群T2DM的发生无关,仅为人群中的基因多态性。     

基因芯片筛查糖尿病线粒体基因突变

目的建立一种快速、准确的高通量检测线粒体DNA突变的基因芯片技术,并探讨这些突变与糖尿病的关系。方法以尼龙膜为介质,通过紫外交联固定28个待测突变位点的野生型和突变型探针,并采用该基因芯片对200例2型糖尿病患者和210名健康对照的线粒体tRNA leu（UUR）基因及ND1基因进行筛查,DNA测序进一步确证突变位点,Mfold和Antheprot软件预测变异型基因及蛋白质二级结构。结果成功研制可检测28个突变位点的线粒体DNA芯片,在糖尿病组检出tRNA leu（UUR）基因13290C突变2例（1．0％）,ND1基因突变23例：G3316A突变6例（3．0％）、13394C突变5例（2．5％）、A4164G突变8例（4．0％）,T4216C突变2例（1．0％）,T3593C（0．5％）和A3606G突变各1例（0．5％）;对照组检出G3316A突变1例（0．5％）、A4164G突变5例（2．4％）。这些突变位点的测序结果与基因芯片检测结果一致。两组间仅13394C突变率差异有统计学意义（P=0．027）。G3316A突变导致丙氨酸→苏氨酸,13394C突变导致酪氨酸→组氨酸,13593C突变导致缬氨酸→丙氨酸,T4216C突变导致酪氨酸→组氨酸,A3606G和A4164G突变分别为亮氨酸和蛋氨酸的无意义突变,前4种突变型的ND1蛋白二级结构不同于野生型。结论线粒体DNA芯片是一种快速可靠的高通量基因突变检测方法,ND1基因13394C突变可能参与了线粒体基因缺陷型糖尿病的发病。     

Hepatitis B virus S gene mutants in infants infected despite immunoprophylaxis

Objective　To assess the correlation between hepatitis B virus (HBV) surface gene mutant infection and hepatitis B (HB) vaccination failure. Methods　Using sera from 106 infants who were born to HBV carrier mothers and failed in HB immunoprophylaxis, HBV S gene was amplified by PCR, transferred to nylon membranes for Southern blots, and then hybridized with oligonucleotide probes. Eleven of non-hybridizing samples were used for DNA sequencing. Results　93.4% (99/106) of the samples were HBV DNA positive, and 30.3% (30/99) failed to hybridize with at least one of the four probes. DNA sequencing confirmed that 10 of the 11 samples had an S gene mutation with amino acid (aa) change. The identified mutants included nucleotide (nt) 546T→A(aa131N→T), nt531T→C (aa126I→T), nt491A→C (aa113T→P), nt491T→A (aa113S→T), nt533C→A (aa127P→T), nt581T→A (aa143S→T), nt636A→T (aa161Y→F), and nt679A→C (aa175L→F). The sequence in one mother-infant pair was completely the same, with mutations at aa131 and aa161. Conclusions　The prevalence of HBV surface mutants is about 30% in the children failing in HB vaccination. HBV mutants can infect infants by maternal-infant transmission.     

伴线粒体基因突变的家族性糖尿病的临床特征

目的探讨由线粒体ｔＲＮＡＬｅｕ（ＵＵＲ）（ｍｔＤＮＡ）３２４３Ａ→Ｇ点突变引起的糖尿病亚型的临床特征。方法按ＷＨＯ的标准，采用基因诊断技术，对１３０例伴有糖尿病家族史的病人，其中包括胰岛素依赖型糖尿病（ＩＤＤＭ）和非胰岛素依赖型糖尿病（ＮＩＤＤＭ）进行筛查。并对其中３例阳性者的家系进行临床及基因分析。结果从１３０例糖尿病患者中共检出４例（３．１％）伴有ｍｔＤＮＡ３２４３点突变的非亲缘关系的病人，然后从其中３例突变病人及其家系中检测出９例线粒体糖尿病。全部患者均为消瘦体型。其中８例伴有神经性耳聋，８例因对口服降糖药继发性失效需改用胰岛素治疗。结论由于这类病人具有母系遗传、耳聋、进行性胰岛素分泌不全等特征，临床上可将这一类型的糠尿病分为一种新亚型－ＭＩＤＤ。     

中国人群中HIV-1辅助受体CCR5基因新突变位点及CCR5-894C缺失基因多态性分析

目的：研究中国人群HIV-1辅助受体CCR5基因编码区新的单核苷酸多态性（SNP）位点;分析CCR5-894C缺失等位基因在中国普通人群和HIV-1高危人群中的分布特点和相关意义。方法：针对CCR5编码区用2对引物进行PCR扩增,设计测序引物对45例汉族人样本进行PCR产物直接测序,用DNAstar分析测序结果,寻找SNP位点。采用错配PCR-RFLP法对中国汉族、蒙族、藏族普通人群,性传播疾病和静脉吸毒高危人群及HIV-1携带者,共627份样品进行了CCR5-894C缺失等位基因分型。结果：在45例汉族人CCR5基因编码区共发现6个SNP位点,4个（184A→G、503G→T、668G→A、99G→T）引起氨基酸改变,两个无义突变;此外还发现1个单碱基缺失（894C缺失）,引起移码突变和提前终止。其中184A→G、503G→T、999G→T三个中国汉族人所特有的SNP位点为首次发现,它们的等位基因频率分别为1.11％,21.1%和10.0％;其中503G→T分布明显不符合Hardy-Weinberg平衡。汉、藏、蒙等民族的普通人群CCR5-894C缺失等位基因频率为1.11％,0.53%和0.在汉族HIV-1性传播、静脉吸毒传播的高危人群中,HIV-1阳性个体和阴性个体间CCR5-89C缺失等位基因频率差异无显著意义,与汉族普通人群比较差异也无显著意义。结论：中国人CCR5基因的SNP位点有自己的特点,共发现4个引起氨基酸改变的SNP位点（其中3个为首次发现）,1个引起移码突变的单碱基缺失。汉族人群中存在CCR5-894C缺失突变,但突变频率很低。这些SNP和缺失突变对于HIV-1感染和艾滋病病程的影响值得进一步研究。     

有家族史的非胰岛素依赖型糖尿病患者线粒体tRNA Leu(UUR) A3243G基因突变的研究

目的 探讨有家族史和无家族史的非胰岛素依赖型糖尿病(NIDDM)患者线粒体tRNA^Leu(UUR) A3243G基因突变的发生率，筛查与糖尿病发生相关的新的线粒体基因突变位点。方法 48例有家族史和44例无家族史的NIDDM患者测 定体重指数(BMI)、口服葡萄糖耐量试验(OGTT)、胰岛素释放试验、糖化血红蛋白(HbA1c)等指标，并应用多聚酶链反应-单链构象多态性(PCR-SSCP)技术对所选糖尿病患者的白细胞线粒体DNA进行基因突变分析。结果 ①两组患者的BMI、血糖、胰岛素、HbA1c无显著性差异。②扩增区域未发现任何线粒体DNA基因突变位点，国内外报道相对较为多见的tRNA^Leu(UUR) 3243A→G基因突变也未在本试验中发现。结论 线粒体tRNA^Leu(UUR) A3243G基因突变糖尿病的发生率很低。     

用位点特异PCR法检测Leber遗传性视神经病家系的mtDNA11778G→A点突变

目的 寻找一种快速、准确、有定量突变比例的简单PCR方法,以识别Leber遗传性视神经病(LH0N)息者所携带的mtDNA ll778G→4A点突变。方法 根据已知致病突变的碱基变化,设计M(突变)和N(正常)引物,分别与反向引物R配对扩增,严格控制退火温度和其他PCR反应条件达到特异扩增。病例组为LH0N家系共10个个体,对照组为40位正常人。结果 在先证者、母系已发病亲属和一个10岁男孩(未发病)体内分别检出突变比例各不相同11778G→A点突变,而在家系的正常配偶、父系子女及40位正常对照组未检出该突变。结论 位点特异PCR是一种不受DNA序列有否限制性内切酶位点的检测突变的方法,适用于LH0N等致病突变明确的遗传病的基因诊断。     

GJB2 (Cx26) gene mutations in Chinese patients with congenital sensorineural deafness and a report of one novel mutation

Background Mutations in GJB2 gene are a major cause of autosomal recessive congenital hearing loss and the cause in some rare cases of the autosomal dominant form. The purpose of this study was to investigate the frequency and the features of GJB2 mutations in the Chinese patients with congenital sensorineural deafness.Methods Using PCR amplifying the entire coding region of GJB2 gene and direct DNA sequencing to analyze mutations in this gene among unrelated 69 cases with autosomal recessive congenital nonsyndromic deafness and 27 cases of dominant congenital deafness and 35 sporadic cases. We also detected mutations in GJB2 in 100 control subjects with normal hearing.Results 17. 4% (12/69) of the probands in the autosomal recessive, 7. 4% (2/27) of dominant families and 5.7% ( 2/35 ) of the sporadic congenital deafness patients had deafness-causing mutations in GJB2, respectively. Nine types of the mutations in GJB2 were detected in the recessive and sporadic group. They consisted of five types of polymorphism, and four types of deafness-causing mutation with homozygous 35delG in 1 sporadic (1/35), and 235delC frameshift mutation in 1 sporadic (homozygotes) and 10 recessive patients (2 heterozygotes and 8 homozygotes), and homozygous 442G→A missense mutation and homozygous 465T→A nonsense mutation in 1 different recessive proband, respectively. The 465T→A that related to recessive deafness was a novel mutation found by this study. The homozygous (10/69, 14. 5%) and the heterozygous (2/69,2.9%) GJB2 mutation in the recessive patients (12/69, 17.4%) and the homozygotes in the sporadic patient (2/35, 5. 7%) all had congenital severe to profound sensorineural hearing loss.511G→A missense mutation and 299 -300delAT frameshift mutation were found in two autosomal dominant congenital deafness families (2/27, 7.4%). The total mutation frequency of GJB2 was 12.2% (16/131) in the Chinese patients with congenital sensorineural deafness and 235delC was the most common deafness-causing mutation. Six types of mutation-5 types of polymorphism and 1 type of heterozygous deletion (235delC) mutation were found in the 100 control subjects. The carry rate of the most frequent type of mutation 235delC was 0. 5% in the controls(1/200 alleles). 109G→A was the most frequent (15/100, 15%) and 79G→A was the second common (8/100, 8%) polymorphism in this population.Conclusions The general mutation rate of GJB2 is 12.2% (16/131) and the 235delC is the most common type of deafness-causing mutation in Chinese patients with congenital hearing loss. 465T→A nonsense mutation that is associated to autosomal recessive deafness is a novel mutation found by this screening. 511G→A and 299-300delAT mutations contribute to autosomal dominant hearing loss. The study further supports the view that the common types of mutation in GJB2 according to different ethnic background and that the mutation prevalence in the East Asian deafness population is lower than that in the white population.     

2 型糖尿病患者线粒体常见基因突变PCR检测的局限性

目的:研究北京地区汉族人群中线粒体DNA(m itochondrial DNA,m tDNA)多位点突变频率与2型糖尿病之间的相关性。方法:采用直接PCR、PCR-限制性片段长度多态性(restriction fragm ent length polymorph ism,RFLP)、PCR-时相温度梯度凝胶电泳(temporal temperature grad ient gel electrophoresis,TTGE)法筛查m tDNA 4977片段缺失、线粒体tRNALeu(UUR)A3243G突变和m tDNA T14577C突变。结果:在250例2型糖尿病患者及142例健康对照外周血基因组总DNA中,未发现m tDNA 4977缺失、线粒体tRNALeu(UUR)A3243G突变及m tDNA T14577C突变。结论:m tDNA 4977缺失、线粒体tRNALeu(UUR)A3243G突变及m tDNA T14577C突变在外周血中没有检出,采用常规PCR法检测2型糖尿病患者外周血线粒体DNA突变具有较大的局限性。     

Mitochondrial DNA mutations in matrilineal nonsyndromic deafness pedigrees of southwest China]

OBJECTIVE: To identify the incidence of the 1555A-->G mutation and explore the audiological features of pedigrees with matrilineal non-syndromic deafness in Southwest of China so as to provide the theoretical evidence for establishing the method of gene diagnosis. METHODS: Six pedigrees with 102 members were evaluated audiologically and clinically. DNA was extracted from their blood samples. All subjects were screened for mitochondrial DNA 1555A-->G mutation by Alw 26I restriction endonuclease digestion. RESULTS: Seventeen maternal relatives of aminoglycoside antibiotic induced deafness (AAID) pedigree 1 and pedigree 2, carried 1555A-->G mutation. 10 maternal relatives of Non-AAID pedigree 6 also carried 1555A-->G mutation. No mutation was found among paternal relatives and pedigrees 3, 4 and 5. CONCLUSION: The same audiological features of these pedigrees are: bilateral and symmetrical progressive sensorineural hearing loss with variable age of onset. The 1555A-->G mitochondrial mutation is one of the hereditary factors for this disorder. 4 Aminoglycoside antibiotic plays an important role in developing deafness. The incidence of the 1555A-->G mutation in AAID and matrilineal non-syndromic deafness pedigrees is fairly high. Screening for mitochondrial 1555A-->G mutation may be of great clinical use fullness.     

Mitochondrial gene defect in patients with chronic progressive external ophthalmoplegia

Objective To detect the gene defect of mitochondrial DNA(mtDNA) from skeletal muscles in 2 patients with chronic progressive external ophthalmoplegia (CPEO).Methods After extraction of mtDNA, Southern hybridization was performed after restrictive digestion by PvuⅡ, EcoRI, Hind Ⅲ, and SacI. Then, we carried out polymerase chain reaction(PCR) and the enzyme digestion of the PCR products. Finally, mtDNA sequencing was done by automatic DNA sequence analyzer. Results In case 1, a 5 kb deletion was found by Southern blot analysis and PCR. And dosage analysis showed a heteroplasmic change with 44% mtDNAs deleted. In case 2, PCR plus restriction endonuclease PvuⅡ digestion demonstrated a mutation which was confirmed by DNA sequencing to be a single base substitution (T→C) inducing a novel PvuⅡ site around 10909 on mtDNA sequence. The laser image analyzer measurement revealed the mutation was almost homologous (99.4% mutant).Conclusions In case 1, a 5 kb deletion found in mtDNA is called "common deletion" according to the literature. In case 2, a novel PvuⅡ site was found. It seems to be a de novo point mutation affecting ND4 in published CPEO research and is first reported in Chinese population. This point mutation does not induce an amino acid(Phe) change according to the published human mitochondrial genetic code as well as the mtDNA sequence. Whether it affects the translation efficiency or transportation of signals between mitochondrial and nuclear genome needs further studies.     

线粒体DNA ND4 12026基因突变与糖尿病

目的 研究线粒体DNADN412026位点在中国上海地区非肥胖2型糖尿病患者中的突变情况。并探讨该位点突变的临床特征。方法 采用PCR-SSCP、PCR-RFLP及PCR产物直接测序等技术检测线粒体DNAND4片段的突变情况。结果 发现286例糖尿病患者血样中有12例患者mtDNAND4基因上12026位点存在AtoG的点突变,导致异亮氨酸错义突变成缬氨酸,而在242例非糖尿病对照组个体中仅1例存在同样突变,对该位点突变的临床分析发现起病年龄低。58%有家族史,需要胰岛素治疗。结论 12026位点AtoG的突变可能与糖尿病的发生有关,并有一定的临床特征。     

Detection of ATM gene mutations in young lung cancer patients: a population-based control study

BACKGROUND: Ataxia-telangiectasia (A-T) is an autosomal recessive disease characterized by neurological and immunological symptoms, radiosensitivity, and cancer predisposition. Heterozygous carriers of risk mutations in the A-T gene are predisposed to epithelial cancers. We initiated a study to elucidate the frequency and clinical relevance of ATM gene mutations in lung cancer patients of the young (LUCY) and compared the results with population-based control subjects from southwest Germany (KORA=Cooperative Health Research in the Region of Augsburg). METHODS: In this study, the clinical relevance of ATM gene mutations (S707P; 1066-6T-->G; 2250G-->A, 7630A-->C, E1978X, R2443X, 3801delG, S49C, and D2625E&A2626P, L1420F, P1045R) in 183 young lung cancer patients (<50 years) is evaluated. The control population was comprised of 200 cancer-free subjects from the KORA study. RESULTS: A total of 25 heterozygous carriers of ATM in the LUCY, respectively; 32 heterozygotes in the KORA group were identified. The observed allele frequencies in the LUCY cases were within the range detected for the control subjects (KORA). Multiple analyses of lung cancer patients who carried at least one risk allele of the ATM did not show significantly elevated or reduced risks. CONCLUSIONS: In this study, 16% of the German control subjects had ATM variants. ATM variants were detected in about 14% of the lung cancer patients and did not differ significantly from the control subjects. In comparison to young lung cancer patients, ATM gene mutations had no detectable relevant modifying effect on lung cancer risk.