Analysis of the insulin-sensitive phosphodiesterase 3B gene in type 2 diabetes

We screened for mutations in the gene of insulin-sensitive phosphodiesterase 3B (PDE3B), which regulates antilipolytic actions of insulin via reduction of intracellular cyclic AMP levels, in Japanese patients with type 2 diabetes mellitus and lipoatrophic diabetes mellitus using single-stranded conformation polymorphism analysis and Southern analysis and investigated frequencies of variable number of tandem repeats. A silent polymorphism at the Arg463 codon (AGG-->AGA) in exon 4 was identified after examining all 16 exons and exon-intron splicing junctions of the gene. This polymorphism was found in 53 of 100 subjects with type 2 diabetes mellitus, 2 of 5 lipoatrophic diabetic patients and 24 of 50 control subjects, without any significant difference in allele frequency between groups. An EcoRI restriction fragment length polymorphism was identified in patients with type 2 diabetes mellitus and control subjects, again with no differences in occurrence. The allelic distribution of two polymorphic tandem repeats sequences in introns 5 and 12 of the gene did not differ significantly between patients with type 2 diabetes mellitus and control subjects. In conclusion, alterations in the PDE3B gene are unlikely to contribute importantly to the pathogenesis of type 2 diabetes mellitus or lipoatrophic diabetes mellitus in Japan.     

A polymorphism in the 5' untranslated region and a Met229→ Leu variant in exon 5 of the human UCP1 gene are associated with susceptibility to Type II diabetes mellitus

Aims/hypothesis. The cumulative effects of several thrifty factors could contribute to the pathogenesis of Type II (non-insulin-dependent) diabetes mellitus. We screened the human UCP1 gene (UCP1) for polymorphisms associated with susceptibility to Type II diabetes. Methods. By using PCR and single-strand conformation polymorphism analysis, UCP1 were screened for mutations in 25 Type II diabetic subjects and 25 healthy control subjects. The allele frequencies of the detected polymorphisms were determined by PCR and restriction fragment length polymorphism analysis in 320 diabetic subjects and 250 control subjects. Results. An A→C transition in the 5' untranslated region (UTR) of exon 1 (112 bp upstream of the translation initiation codon) and a Met²²⁹→Leu variant were detected. The allele frequencies for the C variant and for the Leu²²⁹ variant were higher in the Type II diabetic group than in the control group (p = 0.017 and p = 0.038, respectively). These polymorphisms were in linkage disequilibrium (p < 0.00001). Luciferase assay showed that the former variant in the 5' UTR may affect the promoter activity of UCP1. Conclusion/interpretation. Both the A→C polymorphism and the Met²²⁹→Leu polymorphism of UCP1 are in linkage disequilibrium and could be one of the diabetes associated single nucleotide polymorphisms (SNPs). [Diabetologia (2001) 44: 373–376] Received: 24 August 2000 and in revised form: 17 November 2000     

A common polymorphism of uncoupling protein 2 gene is associated with hypertension

OBJECTIVES: The genes responsible for obesity are also candidate genes for obesity-related conditions, such as hypertension and type 2 diabetes. A functional polymorphism in the uncoupling protein 2 (UCP2) promoter has been reported to be associated with obesity in Caucasians. To clarify the contribution of this polymorphism to obesity and related conditions, we studied the association of the -866 G/A polymorphism of the UCP2 gene with obesity, hypertension and type 2 diabetes mellitus. METHODS: A total of 632 unrelated Japanese subjects were studied: 342 type 2 diabetic patients (among them, 158 patients complicated with hypertension), 156 hypertensive patients without diabetes mellitus and 134 control subjects. The -866 G/A polymorphism of UCP2 was determined by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP). RESULTS: The frequency of the minor A allele was significantly higher in Japanese than in Caucasians (48.9 versus 37.2%, P=0.01). In contrast to the significant association with obesity in Caucasians, the polymorphism was not associated with obesity in Japanese. The polymorphism, however, was significantly associated with hypertension in Japanese (frequency of A allele: 51.8% in hypertensives versus 46.6% in normotensives, P<0.05). No significant difference was observed in body mass index (BMI), fasting insulin level or HOMA-R between patients with different genotypes. CONCLUSION: These data indicate that the polymorphism of the UCP2 gene is associated with hypertension, and suggest the possibility of UCP2 as a target molecule for studies on the etiology and treatment of hypertension.     

树突状细胞表面特异性非整联蛋白外显子4在中国裔丙型肝炎患者中的遗传多态性

目的探讨树突状细胞表面特异性非整联蛋白（DC—SIGN）及其同源物（DC-SIGNR）外显子4遗传多态性在中国裔丙型肝炎患者中是否存在遗传易感性。方法采用PCR结合DNA测序对300例丙型肝炎患者和520名健康人的DC-SIGN和DC-SIGNR外显子4重复序列多态性进行基因分型和测序分析。结果DC—SIGN外显子4基因型与等位基因频率在丙型肝炎患者和健康人群间差异无统计学意义（P〉0．05）。DC-SIGNR外显子4等位基因的频率差异也无统计学意义（P〉0．05）；但9／5基因型分布频率在丙型肝炎患者和健康人群间的差异有统计学意义（P〈0．05）。结论DC-SIGN外显子4遗传多态性与HCV感染易感性无明显相关性；9／5基因型DC-SIGNR外显子4在丙型肝炎患者中的分布频率较高，可能与HCV感染的易感性相关，值得进一步研究。     

2型糖尿病与β细胞素基因外显子1 Cys7Gly多态性的相关性研究

目的探讨β细胞素基因外显子1Cys7Gly多态性与2型糖尿病（T2DM）的关系。方法采用聚合酶链反应,限制性片段长度多态法检测天津地区211名T2DM患者和102名正常对照者β细胞素基因外显子1基因型,比较两组G等位基因频率差异。结果在BMI≥24kg/m^2受试者,对照组G等位基因频率为7.3%,T2DM组为0.4%,两组差异有统计学意义（P〈0.05）。结论β细胞素基因外显子1Cys7Gly多态性可能与部分国人T2DM发生相关,TG基因型在T2DM发病中可能具有一定保护作用。     

内皮细胞型一氧化氮合酶基因多态性与糖尿病肾病的相关性研究

目的：探讨内皮细胞型一氧化氮合酶（eNOS)基因第7外显子894G→T点突变,及其第4内含子的1个27bp的插入／缺失（a/b)多态性,与2型糖尿病肾病（DN）之间的关系。方法：894G→T点突变采用聚合酶链反应限制性片段长度多态性（PCR－RFLP）技术,27bp的a/b多态性采用聚合酶链反应结合4％琼脂糖凝胶电泳分离技术。比较各组间的等位基因频率与基因型频率。结果：（1）早期糖尿病肾病组（DN^ 组）T等位基因及TG基因型频率显著高于糖尿病非肾病患者（DN^-组,P＜0．05）。（2）DN^ 组a等位基因及ab基因型频率显著高于DN^-组（P＜0．05）。（3）DN^ 组的TGab基因型频率亦显著高于DN^-组（P＜0．05）。（4）糖基化血红蛋白（GHbA1c),收缩压（SBP）,总胆固醇（TC）,eNOS基因第7外显子894G→T基因点突变及第4内含子a/b多态性均属糖尿病肾病的独立危险因素。结论：糖尿病患者eNOS基因第7外显子T等位基因及第4内含子a等位基因与DN^ 的发生密切相关,两种等位基因同时存在者,DN^ 发病风险更高。     

Association of His1085His INSR Gene Polymorphism with Type 2 Diabetes in South Indians

Abstract Background and Objective: The INSR gene, which encodes the insulin receptor, is a candidate gene for type 2 diabetes (T2D). The objective of the present study was to sequence some of the crucial exons in the INSR gene such as exon 2, which encodes the insulin-binding domain of the INSR protein, and exons 17-21, which encode the protein tyrosine kinase domain for mutations/polymorphisms, and to study their association with T2D in the South Indian population. Subjects and Methods: The INSR gene was sequenced in 25 normal glucose-tolerant (NGT) and 25 T2D subjects, and the variant found was genotyped by polymerase chain reaction-restriction fragment length polymorphism in 1,016 NGT and 1,010 T2D subjects, randomly selected from the Chennai Urban Rural Epidemiology Study. Results: Only one previously reported polymorphism, His1085His [rs1799817, (C→T)], in exon 17 was detected by sequencing. The frequency of the "T" allele of the His1085His polymorphism was significantly lower in the T2D subjects (31%) compared with the NGT subjects (35%) and showed significant protection against diabetes (odds ratio 0.85, 95% confidence interval 0.75-0.97, P=0.019). Regression analysis according to a recessive model taking the CC+CT genotype as the reference showed that the TT genotype was protective against diabetes (odds ratio 0.71, 95% confidence interval 0.50-0.99, P=0.048). Adjusting this P value by the number of competing models (three) using Bonferroni's correction, we found that the association finding did not remain significant. Conclusions: The "T" allele of the His1085His polymorphism in the INSR gene shows significant protection against diabetes. This study gains importance because there are no data available to date on the role of INSR variants in T2D in the Indian population.     

Role of type IV collagen in prolactin release from anterior pituitaries of male rats

We previously demonstrated that laminin, a component of basement membranes, modulates pituitary hormone secretion. In the present study, we evaluated the effect of type IV collagen, another component of this membrane, on the release of prolactin (PRL) by anterior pituitary gland from adult male rats. Hemipituitaries were incubated for 3 h with type IV collagen or antibodies against it and PRL release was studied. Rabbit IgG to type IV collagen at concentrations of 10⁻⁷−10⁻⁵ M had a significant stimulatory effect on PRL release, in comparison to normal rabbit serum IgG or medium alone used as controls. Type IV collagen induced a significant inhibitory effect on basal release of PRL at a concentration of 30 μg/mL. A slight decrease in PRL release was detected in thyrotropin-releasing hormone-stimulated hemipituitaries incubated with type IV collagen at all concentrations used. These results suggest that type IV collagen, similar to laminin-1, modulates PRL released from hemipituitaries, in vitro.     

Variant sequences of the Hexokinase II gene in familial NIDDM

Summary Hexokinase II (HKII) plays a central role in the intracellular metabolism of glucose in skeletal muscle, catalysing the phosphorylation of glucose to glucose 6-phosphate. It is therefore considered to be a potentially important candidate gene in the development of insulin resistance and non-insulin-dependent diabetes mellitus (NIDDM). The aim of this study was to screen the HKII gene for mutations in NIDDM subjects from insulin-resistant families. Insulin sensitivity was assessed in unaffected first degree relatives from families with two or more living NIDDM subjects, and 15 families were identified as being insulin resistant. In 15 NIDDM subjects (one from each family) and 4 normoglycaemic control subjects, all 18 exons of the HKII gene were amplified by the polymerase chain reaction, and the products screened for mutations using a combination of single-stranded conformational polymorphism analysis and direct sequencing. Six sequence variations were detected in the NIDDM subjects; four silent polymorphisms [GAT vs GAC at codon 251 in exon 7, AAT vs AAC at codon 692 in exon 15, CCG vs CCC at codon 736 in exon 15, and CTG vs CTA at codon 766 in exon 16]; a single base change [TC], 22 base pairs distal to the exon-intron junction of exon 17 in the 5-splice donor; and a single amino acid substitution [Gln¹⁴²His] in exon 4, which was identified in 6 of the 15 NIDDM subjects. The frequency of the mutated codon 142 allele however, was comparable between NIDDM subjects with familial NIDDM (n=56) and normoglycaemic control subjects (n=48) (18.8% and 14.6% for NIDDM subjects and control subjects respectively; ²=0.6, p>0.25). In addition, measures of insulin sensitivity were comparable in normal glucose tolerant subjects with (n=20) and without (n=40) the codon 142 polymorphism. In conclusion: (1) mutations in the coding regions of the HKII gene are unlikely to be major determinants in the development of insulin resistance and familial NIDDM; although (2) the influence of the codon 142 mutation in combination with other abnormalities of the insulin-signalling pathway on insulin action remain to be addressed.Abbreviations bp Base pair - HKII Hexokinase II - NIDDM non-insulin-dependent diabetes mellitus - PCR polymerase chain reaction - SSCP single-strand conformational polymorphism - WHR waisthip ratio - OGTT oral glucose tolerance test - ITT insulin tolerance test - ANCOVA analysis of covariance - MODY maturity onset diabetes of the young     

HepG2/erythrocyte glucose transporter (GLUT1) gene in NIDDM: a population association study and molecular scanning in Japanese subjects

Summary To evaluate the role of mutations in the glucose transporter (GLUT1) gene in Japanese patients with non-insulin-dependent diabetes mellitus (NIDDM), we first conducted a population association study using the XbaI polymorphism of the gene. A polymerase chain reaction (PCR)-based assay was developed and used for the analysis. When analysed in 91 diabetic patients and 87 non-diabetic control subjects, the distribution of the genotype frequency was significantly different between the two groups (p=0.0025). The (–) allele was significantly associated with NIDDM (odds ratio 2.317, 95% confidence interval 1.425–3.768). To identify possible mutation(s) in the GLUT1 gene, which was in linkage disequilibrium with the (–) allele, all ten exons of the gene were analysed by PCR single-strand conformation polymorphism (SSCP) analysis in 53 diabetic patients with at least one (–) allele. Variant SSCP patterns were detected in exons 2, 4, 5, 7, 9 and 10. Sequence analysis revealed that all the variants represented silent mutations. One of the variants in exon 2, GCT (Ala¹⁵)GCC(Ala), created a HaeIII restriction site. This polymorphism was common in Japanese subjects with heterozygosity of 0.36 and polymorphism information content 0.29. We conclude that the structural mutation of GLUT1 is rare and not likely to be a major genetic determinant of NIDDM in Japanese subjects. The Xbal (–) allele of the GLUT1 gene appeared to be a genetic marker of NIDDM in Japanese subjects. The possibility of the presence of mutation(s) in the regulatory region of the gene or in another locus nearby could not be excluded.Abbreviations NIDDM Non-insulin-dependent diabetes mellitus - PCR polymerase chain reaction - SSCP single strand conformation polymorphism - BMI body mass index - RFLP restriction fragment length polymorphism - TRE TPA-responsive elements - GLUT1 glucose transporter 1     

Calpain 1 O基因多态性与中国人2型糖尿病遗传易感性的相关性研究

目的 了解Calpain 10基因对中国汉族人2型糖尿病遗传易感性的影响。方法 采用病例对照研究方法：以聚合酶链式反应－限制性内切酶长度多态性（PCR－RFLP）技术，对211例2型糖尿病患者及127例正常对照Calpain 10基因SNP43及SNP19多态性进行基因分型。结果 同对照组相比，SNP43的G等位基因频率在2型糖尿病人群中显著升高（91．9％ vs 85.8%,P=0.01)。但SNP19位点等位基因频率在上述两组中的频率分布无显著差异。此外，本研究还观察到在正常对照组中，SNP43GG基因型与体重指数和腰－臂围比值增加相关。结论 Calpain 10基因SNP43位点G等位基因可直接或与其他糖尿病基因相互作用决定汉族人2型糖尿病的遗传易感性。     

Human uncoupling protein 2 and 3 genes are associated with obesity in Japanese

Human uncoupling proteins (UCPs) are mitochondrial proteins that are involved in the control of energy metabolism and the pathophysiology of obesity. Although there have been several reports on the association between the UCP2/UCP3 locus and the obesity, there have been no haplotype-based case-control studies with gender-specific analysis. The aim of this study was to examine whether there is an association between the UCP2/UCP3 locus and the obesity in the Japanese population when using a single nucleotide polymorphism (SNP)-based and haplotype-based case-control study with gender-specific analysis. We examined a group consisting of 551 subjects, of which 369 were non-obese and 182 were overweight and/or obese. We selected one nonsynonymous SNP (rs660339: Ala55Val) as a genetic marker. Genotyping for all subjects was performed by the TaqMan polymerase chain reaction (PCR) method. Although the overall distributions of genotype and allele were not significantly different between the non-obese and the obese groups, the overall distributions of the genotype were significantly different in men (P = 0.030). In the obese group, male subjects with the Val allele were significantly more frequent in both association studies. There was a significant difference in the overall distribution of the haplotype (UCP3 rs180049, UCP3 rs2075577, UCP2 rs660339) between the weight groups (P = 0.010), and in women, there was a significant difference (P = 0.042) in the overall distribution of the haplotype (UCP3 rs2075577, UCP2 rs660339). Nonsynonymous rs660339 in the human UCP2 gene in men, and the haplotype (UCP3 rs2075577-UCP2 rs660339) in women might be good obesity markers.     

对氧磷酯酶192Gln/Arg基因多态性与2型糖尿病合并冠心病的相关性研究

目的　探讨对氧磷酯酶 192Gln/Arg基因多态性与 2型糖尿病合并冠心病的关系。　方法　采用多聚酶链反应 限制性片段长度多态性 (PCR RFLP)法检测 10 4例健康对照者 (作为正常对照组 )和 80例 2型糖尿病、96例 2型糖尿病合并冠心病 (CDH)患者PON1 192位点的多态基因型。测量体重指数、总胆固醇、甘油三酯、高密度脂蛋白、低密度脂蛋白、载脂蛋白AI及载脂蛋白B。　结果　 ( 1)中国汉族人PON1 192位点QQ、QR、RR基因型频率及Q、R等位基因频率 :2型糖尿病合并CHD组与正常对照组比较差别有显著性 ;与单纯糖尿病组比较差别无显著性。 ( 2 )中国人与白种人PON1 192位点基因型频率及等位基因频率比较差别非常显著。 ( 3)含R等位基因的基因型QR、RR是 2型糖尿病合并CHD的独立危险因素。　结论　对氧磷酯酶 192Gln/Arg基因多态性与 2型糖尿病合并CHD相关。     

A genetic variation in the 5 ′ flanking region of the UCP3 gene is associated with body mass index in humans in interaction with physical activity

Aims/hypothesis. In obese French Caucasian subjects we previously described a silent UCP3 Tyr99Tyr mutation, associated with body mass index. We hypothesised that an unknown polymorphism in the vicinity of the gene could contribute to obesity.¶Methods. Morbidly obese subjects were screened for mutations in 1 kb upstream from the UCP3 gene. Association studies were done between a variant and obesity in 401 morbidly obese and 231 control subjects.¶Results. We detected three rare genetic variants and one polymorphism: a + 5 G→A in exon 1, a –155 C→T, a –439 A insertion and a –55 C→T located 6 bp from the putative TATA box. This variant was in linkage disequilibrium with the Tyr99Tyr polymorphism. Frequencies of the variant allele at the –55 locus were similar in the obese and control groups (0.23 vs 0.21). The –55 polymorphism was associated with BMI in the obese group (p = 0.0031): BMI was higher in TT than in CC or CT patients. Likewise control subjects with a TT genotype had a higher BMI (p = 0.03). In the obese group, homozygocity for this variant is a risk factor for high BMI (odds ratio: 1:75, p = 0.02). Obese patients were divided into tertiles according to physical activity. In the group with a wild C/C genotype, BMI was negatively associated with physical activity (p = 0.015).¶Conclusion/interpretation. The C→T polymorphism in the 5 ′ sequences of the UCP3 gene might contribute to the corpulence in obese and normal weight subjects and alter the benefit of physical activity. The UCP3 gene can be considered as a gene modifying corpulence. [Diabetologia (2000) 43: 245–249]     

Amylin gene promoter mutations predispose to Type 2 diabetes in New Zealand Maori

AIMS/HYPOTHESIS: Amylin gene mutations are known to predispose Chinese and Japanese subjects, but not Caucasian subjects, to Type 2 diabetes. New Zealand Maori, who have a high prevalence of Type 2 diabetes, have genetic origins in South East Asia. Amylin gene mutations could therefore predispose New Zealand Maori to Type 2 diabetes. METHODS: The amylin gene was screened for mutations in the proximal promoter region, exons 1 and 2, intron 1, and coding region of exon 3 by polymerase chain reaction amplification and direct sequencing of 131 Type 2 diabetic Maori patients and 258 non-diabetic Maori control subjects. RESULTS: We identified three new amylin gene mutations: two mutations in the promoter region (-215T>G and -132G>A) and a missense mutation in exon 3 (Q10R). The -215T>G mutation was observed in 5.4% of Type 2 Maori diabetic patients and predisposed the carrier to diabetes with a relative risk of 7.23. The -215T>G mutation was inherited with a previously described amylin promoter polymorphism (-230A>C) in 3% of the Maori with Type 2 diabetes, which suggests linkage disequilibrium exists between these two mutations. The -230A>C polymorphism on its own, however, was not associated with Type 2 diabetes in Maori subjects. The -132G>A and Q10R mutations were both observed in 0.76% of Type 2 diabetic patients and were absent in non-diabetic subjects. CONCLUSION/INTERPRETATION: The amylin gene mutations identified in this study are associated with Type 2 diabetes in 7% of Maori. Amylin is likely to be an important susceptibility gene for Type 2 diabetes in Maori people.     

No evidence for involvement of the promoter polymorphism -866 G/A of the UCP2 gene in childhood-onset obesity in humans.

Recently, an association between obesity and the G-allele of the - 866 G/A polymorphism in the promoter region of uncoupling protein-2 gene (UCP2) was reported. Both allele frequencies and genotype distributions for this polymorphism differed between obese individuals and never-obese controls. We attempted to confirm this finding. Genotyping was performed by polymerase chain reaction with subsequent restriction fragment length polymorphism analysis (PCR-RFLP). We analysed transmission disequilibrium of the (wild type) G-allele for 200 extremely obese children and adolescents from 93 concordant sib pair families using the pedigree disequilibrium test. Additionally, using a one-sided asymptotic Pearson's chi 2-test, we tested whether the G-allele occurs more frequently in 277 extremely obese children and adolescents (including the 93 index patients of the concordant sib pairs) than in 188 never-obese controls. The one-sided asymptotic Cochran Armitage trend test was used to determine differences in genotype frequencies between extremely obese and healthy underweight individuals. The PDT analysis revealed no evidence for transmission disequilibrium in obesity. Allele and genotype frequencies did not differ between the extremely obese and never-obese subjects. In conclusion, we cannot confirm the results of ) in our young sample.     

Putative role of polymorphisms in UCP1-3 genes for diabetic nephropathy

Increased production of reactive oxygen species (ROS) has been suggested as a cause of diabetic complications. Uncoupling proteins (UCPs) have been ascribed a role in reducing the formation of ROS, and genetic variation in genes encoding for UCPs could thus be putative candidate genes for diabetic nephropathy. To test this hypothesis we searched for association between the A-->G (-3862) variant in UCP1, the insertion/deletion (I/D) polymorphism in exon 8 in UCP2, and the C-->T (-55) polymorphism in UCP3 and diabetic nephropathy in 218 diabetic patients with normal urinary albumin excretion rate (AER), 216 with micro- or macroalbuminuria, and in 106 control subjects without a family history of diabetes. We did not find any association between the different polymorphisms and diabetic nephropathy, nor did we observe any difference in AER among carriers of different UCP1-3 genotypes. We could, however, confirm the reported association between BMI and the UCP3 -55 C-->T polymorphism; patients carrying the T allele had higher BMI than patients homozygous for the C allele (26.4+/-4.2 vs. 25.3+/-4.3 kg/m(2); P=.01). We conclude that studied polymorphisms in the UCP1-3 genes do not play a major role in the development of micro- or macroalbuminuria in Scandinavian diabetic patients.     

An uncoupling protein 2 gene variant is associated with a raised body mass index but not Type II diabetes

Aims/hypothesis. Linkage between markers close to the uncoupling protein 2 and 3 genes (11q13) and resting metabolic rate and a pre-diabetic phenotype have been found. The syntenic region in mouse has been found to be linked to quantitative traits associated with obesity and diabetes. UCP2 and UCP3 could therefore have an important role in body weight regulation and susceptibility to diabetes. We investigated a recently identified variant of the UCP2 gene in exon 8 as a marker for glucose and weight homeostasis. Methods. Length variation of the UCP2 exon 8 variant was studied by the polymerase chain reaction and agarose gel electrophoresis. Sequence variants of the UCP3 gene were sought by semi-automated DNA sequencing. Results. In 453 South Indian subjects, we found an association in women between the UCP2 exon variant and body mass index (p = 0.018). These findings were replicated in a separate group of South Indian subjects (n = 143, p < 0.001) irrespective of sex. Although no association was found between the UCP2 exon 8 variant and overt obesity in British subjects, the UCP2 genotype of obese women (n = 83) correlated with fasting serum leptin concentration (p = 0.006) in the presence of extreme obesity. These observations could not be explained by tight linkage disequilibrium with a coding region variant in the region of the UCP3 gene of biological significance. Lastly, no association was found between UCP2 and Type II (non-insulin-dependent) diabetes using either a family based design (85 families) or case control study (normal glucose tolerance n = 335, impaired glucose tolerance n = 42, Type II diabetes n = 76). Conclusion/interpretation. We have described a UCP2 gene exon 8 variant that may affect susceptibility to weight gain by influencing regulation of leptin. [Diabetologia (1999) 42: 688–693] Received: 14 September 1998 and in final revised form: 25 January 1999     

Association of PAX4 gene R192H polymorphisms in Chinese Han type 2 diabetes

The purpose of this study was to explore whether PAX4 gene R192H polymorphism plays a role in type 2 diabetes in Chinese Han population, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technology to detect R192H polymorphism in exon 5 of PAX4 gene in 410 cases of patients with type 2 diabetes and 95 cases of non-diabetic controls from January 2014 to January 2015. There are no significant differences in the genotypes or allele frequencies between type 2 diabetes mellitus (T2DM) and non-diabetic controls about PAX4 R192H polymorphism. Similarly, no statistical differences were observed in the T2DM and non-diabetic controls when adjusting for gender stratification and age stratification. The comparisons on the subjects in clinical characteristics including blood glucose, glycated hemoglobin, cholesterol, triglycerides, high-density lipoprotein cholesterol, and systolic blood pressure showed no difference between carriers with the GA and AA genotype except diastolic blood pressure (p value =?0.038). PAX4 gene exon 5 R192H polymorphism was not associated with type 2 diabetes in Chinese Han population.     

CTLA-4基因外显子1A/G49多态性与1型糖尿病的相关性研究

目的 探讨细胞毒性T淋巴细胞相关抗原4（CTLA－4）基因外显子1的49位点A／G多态性与中国汉族人1型糖尿病（DM）的关系。方法 采用多聚酶链式反应限制性片段长度多态性（PCR－RFLP）技术对33例典型1型DM患者、57例成人晚发自身免疫性糖尿病患者（LADA)和84例健康对照者分析CTLA－4基因外显子1的49位点基因型。结果 1型DM患者的CTLA－4／G^49等位基因频率显著高于对照组（P=0.0005)，而典型1型DM和LADA两组间无显著性差异（P＝0.097)；ICA和GADAb阳性率与G^49无明显相关性（分别为P＝0.065,P=0.066)。结论 CTLA－4基因外显子1多态性与中国汉族人1型DM有关，G^49等位基因是1型DM的独立危险因素之一。