线粒体DNA ND-1基因点突变与2型糖尿病的关系

2型糖尿病患者中线粒体DNA（mtDNA)3316G→A，3316G→A，3394T→C突变频率分别为3.9%(6/152)和5.3%(8/152)，显著高于正常对照者及冠心病患者，提示mtDNA3316G→A，3394T→G突变与2型糖尿病相关。     

糖尿病与线粒体ND1点突变的关系

目的探讨湖北省线粒体基因的热点突变区域ND1点突变(3243,3316,3394,3593)与老年2型糖尿病的关系。方法采用聚合酶链反应-限制性片段长度多态性法对无血缘关系的134例老年糖尿病患者及152例正常对照个体的血细胞线粒体DNA进行突变分析。结果病例组中3316G→A点突变率为3·7%,3394T→C点突变发生率为3·0%,而对照组3316和3394的突变率分别为0·66%和0,3394组间差异比较均有显著性(P<0·05)。病例组中3593点突变发生率为0·75%,对照组未见该突变,两组间差异无显著性。未发现3243的突变。结论线粒体DNA3394T→C突变与老年线粒体糖尿病的发生与发展有关,并起着重要作用。     

家族性糖尿病人群中线粒体ND-1基因点突变的分析研究

目的了解线粒体ND-1基因mt3316G→A、mt3394T→C变异在中国家族性糖尿病人群中的发生率及其临床特点。方法应用PCR-RFLP结合直接测序方法对随机抽取的无亲缘关系的770个糖尿病家系的先证者及309例非糖尿病对照者进行线粒体基因mt3316G→A、mt3394T→C变异的筛查。结果在糖尿病先证者组中发现17例（2.21%）mt3316G→A变异,18例（2.34%）mt3394T→C变异;在正常对照组中分别发现5例（1.62%）和6例（1.94%）变异携带者,变异的发生率在两组间差异无统计学意义。在糖尿病先证者组见到2例同时携带上述两种变异者。伴mt3316G→A或mt3394T→C突变的糖尿病组与无该变异的糖尿病组之间的临床特点（年龄、体质指数、胰岛素抵抗指数）比较差异无统计学意义。结论线粒体ND-1基因mt3316G→A,mt3394T→C变异可能不是中国人线粒体糖尿病发病的致病原因,而是中国人线粒体的基因多态。     

母系遗传糖尿病线粒体基因突变的观察

采用PCR-RFLP、DNA直接测序技术对14个有明确母系遗传史的糖尿病家系进行线粒体基因筛查。结果14例先证者及对照组均未检出A3243G等3个线粒体基因突变位点。家系成员发现携带G3316A突变，T3394C突变，三例均为健康携带者。结论G3316A突变、T3394C突变不是糖尿病的独立致病因素。     

2型糖尿病人群线粒体基因突变的研究

目前已知的几种单基因突变糖尿病(DM)中，线粒体tRNA^Leu(UUR)基因3243A→G点突变最为多见，已在不同种族中被发现。本研究对线粒体基因突变热点区域一tR—NA^Leu(UUR)基因及其邻近区域内的4个位点(np3243、np3316、np3394、np3426)进行筛查，旨在探讨线粒体基因突变在我国2型糖尿病(T2DM)患者中的存在情况。     

老年2型糖尿病患者线粒体ND1基因常见突变位点的快速筛查

2型糖尿病是慢性代谢疾病，呈高龄人群高发病率的特点，尤其是持续高血糖所引发的心血管疾病、终末期肾病等并发症严重困扰着老年2型糖尿病患者。线粒体基因缺陷是其遗传易感因素之一，在诸多报道的突变位点中，以位于tRNA leu（UUR）基因3243（A—G）突变及ND1基因的3316（G→A）、3394（T→C）和3593（T→C）突变最为常见。我们以老年2型糖尿病为研究对象，     

线粒体DNA变异与老年2型糖尿病患者易感性的相关性

目的 研究湖北地区老年2型糖尿病(T2DM)患者中线粒体基因突变的发生率及其相关性.方法 采用PCR-RFLP、基因测序技术,对175例老年T2DM患者和200例糖耐量正常的健康老年对照组进行检测.结果 MIND1 3316(G→A)、MTTL1 3243(A→G)、MIND13394( T→C)、MIND14216(T→C) MIND14164(A→G)和MIND2 5178( T→C)变异率分别为3.26％、2.72％、1.71％、4％、34.9％;对照组检出3316(G→A)突变2例(0.99％)、4164 5例(0.99％)、5718(T→C)变异64例(32.3％),未检出3394、4216的点突变;两组间3394(T→C)变异率差别有统计学意义(P＜0.05);且T2DM组5178A基因型血清TC水平低于5178C基因型(P＜0.05),但TG、LDL-C、HDL-C、apoA、apoB、Lp(a)水平两组无统计学意义.结论 3394( T→C)与老年T2DM患者的易感性有一定关联,5178(T→C)变异与湖北地区老年汉族人T2DM的脂代谢相关.     

线粒体DNA3161-3610片断基因突变与糖尿病的关系

104例糖尿病（DM）患者和50名正常无DM家族史对照者的基因测序研究显示，线粒体DNA3316G→A伴随3290 T→C、3421G→A点突变；3497C→T和3571C→T同时基因突变可能与DM发生有关。     

浙江地区汉族人线粒体DNA ND1基因T3394C突变与老年2型糖尿病

目的 探讨线粒体DNA ND1基因T3394C突变与老年2型糖尿病的关系. 方法 采用聚合酶链反应(PCR)产物直接测序法对340例无血缘关系的2型糖尿病患者(其中老年糖尿病组90例,非老年糖尿病组250例)和265例健康对照者(老年健康对照组130例,非老年健康对照组135例)的血细胞线粒体DNA进行突变位点检测,并用DNASTAR和Antheprot 5.0软件分析突变位点. 结果 老年糖尿病组、老年健康对照组和非老年糖尿病组分别检出5例、1例和2例T3394C突变.T3394C突变在老年糖尿病组和老年健康对照组之间分布差异有统计学意义(P＜0.05),在老年糖尿病组和非老年糖尿病组之间分布差异也有统计学意义(P＜0.05).蛋白质结构预测显示T3394C突变引起ND1蛋白二级结构改变. 结论 线粒体DNA ND1基因T3394C突变可能与老年2型糖尿病的发生有关.     

中国人群线粒体基因C3394T及A12026G突变与2型糖尿病相关性的Meta分析

目的 研究中国人群线粒体基因C3394T及A12026G突变与T2DM相关性。方法检索中国知网、万方、维普、Pubmed数据库,对2001-2013年中国人群线粒体基因C3394T、A12026G突变与T2DM相关性的随机对照试验（RCTs）文献进行检索。经质量评价和资料提取后,对符合质量标准的RCTs进行Meta分析。结果 共纳入11个RCTs。7个RCTs结果显示,C3394T突变合并OR（95% CI）为7.48（3.17-17.76）,4个RCTs结果显示,A12026G突变合并OR（95% CI）为1.88（1.14-3.11）。 结论 中国人群线粒体基因C3394T及A12026G突变与T2DM有相关性,且是其发病的危险因素之一。     

Variation of mitochondrial gene and the association with type 2 diabetes mellitus in a Chinese population

Mitochondrial DNA (mtDNA) variants have been implicated in many diseases including diabetes mellitus. To explore whether these genetic variants contribute to the susceptibility for type 2 diabetes mellitus (T2DM) in a Chinese population, a total of 184 T2DM cases and 279 matched healthy controls were recruited. PCR restriction fragment length polymorphism (PCR-RFLP) analysis and DNA sequencing were used to determine the variants of mtDNA (including T16189C, G3316A, T3394C, A14693G, A3243G and C1310T). Some of them were further analyzed by mfold or tRNA-scan-SE software. A homoplastic A14693G, for the first time, was found in 4 of 184 Chinese cases, the frequency of A14693G and T3394C was 2.17% and 2.72%, respectively, in patients but not in the controls. Secondary structure prediction revealed that there were obvious conformational changes in T3394C mutant ND1 versus wild type and A14693G mutant tRNA(Glu) protein versus wild type, providing additional clues to the disease pathogenesis although A3243G and C1310T mutations were not detected in any patients in the two groups. The 16189 variant among type 2 diabetes was more prevalent than in controls (36.9% versus 28.7%, P=0.039), and stepwise multiple regression analysis showed that the 16189 variant was an independent factor contributing to HOMA-IR (R(2)=0.043, P=0.037). Our results suggest that the mutations of T3394C and A14693G may contribute to genetic predisposition to T2DM, with the T16189C variant being associated with insulin resistance.     

Novel mutations found in mitochondrial diabetes in Chinese Han population

Mitochondria provide cells with most of the energy in the form of ATP. Mutations in mitochondrial DNA (mtDNA) are associated with type 2 diabetes mellitus (T2DM) because ATP plays a critical role in the production and the release of insulin. To systematically determine mutant loci and to investigate their association with T2DM in Chinese Han population, 17 commonly reported mutant loci were screened in 236 cases of T2DM and 240 normal controls by PCR-RFLP, allele-specific PCR (AS-PCR) and DNA sequencing methods. Biological softwares were used to analyze the secondary structure of DNA, RNA and the corresponding proteins for missense mutations. Sixteen mutant loci were detected in total, of which five were novel, GenBank accession nos. were DQ092356, DQ473644 and DQ473645; they were mainly in16S rRNA, ND1 and ND4 gene. There was significant difference between the two groups for ND1 and ND4 genes mutation frequencies (ND1: P=0.001, OR=3.944, 95% CI 1.671-9.306; ND4: P=0.010, OR=5.818, 95% CI 1.275-26.537). No significant association was observed between the two groups for 5178A/C polymorphisms (P=0.418). Our study suggested that T3394C and A12026G might be associated with T2DM in Chinese Han population, and T2DM with mtDNA variant should be considered mitochondrial diabetes.     

Mitochondrial gene mutations in gestational diabetes mellitus

Mitochondrial DNA mutations have been implicated in many diseases including diabetes mellitus. Although gestational diabetes mellitus (GDM) has been suggested to have genetic determinant and to be etiologically indistinct with non-insulin-dependent diabetes mellitus (NIDDM), its association with mitochondrial gene mutations is still unknown. In this study, 137 patients with GDM and 292 non-diabetic pregnant controls were examined for mitochondrial DNA mutations from the nucleotide 3130-4260 encompassing tRNA-Leu gene and adjacent NADH dehydrogenase 1 gene by polymerase chain reaction, single-stranded conformation polymorphism, restriction fragment length polymorphism and DNA sequencing. One heteroplasmic mutation at the position of 3398 (T-C), which changed a highly conserved methionine to threonine in NADH dehydrogenase subunit 1, was identified in 2.9% GDM patients but not in the controls, indicating its association with GDM (P = 0.01). Two novel mutations, a heteroplasmic C3254A and a homoplasmic A3399T, were also found in GDM subjects, the functional meaning of which merits further investigation. G3316A and T3394C mutations implicated in NIDDM, were seen at higher frequencies in patients with GDM than the controls. Our results suggest that mitochondrial DNA mutations may contribute to the development of GDM in some patients.     

线粒体基因5个位点与2型糖尿病早发的关联研究

用PCR-RFLP及DNA测序方法对湖北省汉族人群无血缘关系的102例发病年龄≤45岁2型糖尿病患者及104例正常对照个体的线粒体DNA tRNA Leu（UUR）基因及ND-1基因5个位点进行突变分析。实验组检出3714（A→G）突变2例,两组间仅nt3316（G→A）突变的发生率有统计学差异。推测该位点变异可能与某些核基因或环境因素协同与汉族人群中的线粒体糖尿病的早发及发展有关。     

中国汉族人群脂联素+276位点基因多态性与2型糖尿病相关性的meta分析

目的通过meta分析评估中国汉族人群脂联素基因(adiponectin,ADIPOQ)+276G/T(rs1501299)位点单核苷酸多态性与2型糖尿病(T2DM)的相关性。方法检索自2000年1月1日至2018年12月31日PubMed、Ovid、CBM、Springer、CNKI和WanFang Data中关于中国汉族人群脂联素基因rs1501299(+276G/T)与2型糖尿病相关性的病例-对照研究,并辅以文献追溯。采用Review Manager 5.3软件进行meta分析。结果共纳入13项研究,其中T2DM患者3 384例,健康对照者3 187例。meta分析结果显示,在隐性遗传模式下,两组差异有统计学意义[OR=1.29,95%CI(1.13, 1.49),P<0.05]。该位点基因多态性meta分析结果发表偏倚较小,研究纳入的样本量大、精度较高,所有研究组都具有较好代表性。结论中国汉族人群脂联素基因+276G/T位点基因多态性与2型糖尿病可能具有相关性。     

Relationship between polymorphisms 804C/A and 252A/G of lymphotoxin-alpha gene and -308G/A of tumor necrosis factor alpha gene and diabetic retinopathy in Japanese patients with type 2 diabetes mellitus

To clarify whether polymorphisms of the lymphotoxin-alpha (LTA) gene and tumor necrosis factor alpha (TNF-alpha) gene were related to diabetic retinopathy (DR), we performed a case-control study in 251 Japanese patients with type 2 diabetes mellitus participating in a multicenter research protocol. Genetic analyses were performed by using a fluorescent allele-specific DNA primer assay system. Diabetic retinopathy was diagnosed in a masked manner by an independent ophthalmologist using fundus photographs and was classified as nondiabetic retinopathy (NDR), nonproliferative retinopathy (NPDR), and proliferative retinopathy (PDR). The results showed that the genotype frequencies of 804C/A in exon 3 and 252A/G in intron 1 of the LTA gene were not significantly different among patients with NDR, NPDR, and PDR. A allelic frequency of the TNF-alpha gene (-302A/G in promoter) was also identical among NDR, NPDR, and PDR groups. Multivariate logistic regression analyses showed that significant associations with DR were glycosylated hemoglobin level and diabetes duration, but not polymorphisms of the LTA gene or TNF-alpha gene. In conclusion, the present study showed no association between polymorphisms 804C/A and 252A/G of the LTA gene and -302A/G of the TNF-alpha gene and DR in Japanese type 2 diabetic patients.