Diabetes In Chinese Han Population Research Articles

Association between Single Nucleotide Polymorphism rs9891119 of STAT3 Gene and the Genetic Susceptibility to Type 2 Diabetes in Chinese Han Population from Guangdong.

Background The aim of this study was to investigate the association between single nucleotide polymorphism (SNP) rs9891119 of the signal transducer and activator of the transcription 3 (STAT3) gene and genetic susceptibility to type 2 diabetes in Chinese Han population from the Guangdong province. Objective The aim of the present study was to explore the relationship between single nucleotide polymorphism rs9891119 of STAT3 gene and type 2 diabetes mellitus (T2DM), which provides a basis for molecular genetic research on the pathogenesis of T2DM in Chinese Han population. Methods In our case-control study, the SNP rs9891119 was picked out from the STAT3 gene and the SNP genotyping was performed by using the SNPscan™ kit in 1092 patients with type 2 diabetes as cases and 1092 normal persons as controls. The distributions of genotype and allele frequencies in two groups were analyzed by SPSS 20.0 software. Results Our results showed that the alleles of A and C of rs9891119 of the STAT3 gene were 54.3 and 45.7% in patients with type 2 diabetes, while 55.5% and 44.5% in the normal persons, which have no statistical significance (P > 0.05). There were also no significant differences in AA, AC, and CC genotype frequencies between type 2 diabetes patients and normal persons. There were no significant differences in codominant, dominant, recessive, and overdominant genetic models of SNP rs9891119 before and after adjusting the covariant factors (P > 0.05). Conclusions Therefore, genetic susceptibility to type 2 diabetes may be not associated with SNP rs9891119 of the STAT3 gene in Chinese Han population from the Guangdong province.

Evaluation of the role of B7-H3 haplotype in association with impaired B7-H3 expression and protection against type 1 diabetes in Chinese Han population

BackgroundType 1 Diabetes (T1D) is a T cell-mediated autoimmune disorder caused by the destruction of insulin-secreting cells. B7-H3 (CD276) plays a vital role in T cell response. However, B7-H3 expression and its clinical significance in T1D remain unclear. The aim of this study was to investigate the correlations between the expression of B7-H3 and clinical parameters in T1D patients. The possible role of B7-H3 gene variants with T1D was also discussed.MethodsFour B7-H3 single nucleotide polymorphisms (SNPs) were genotyped in 121 T1D patients and 120 healthy controls by polymerase chain reaction (PCR) direct sequencing. Expression of membrane B7-H3 (mB7-H3) in peripheral blood lymphocytes was determined by flow cytometry. Levels of soluble B7-H3 (sB7-H3) in serum were analyzed by enzyme linked immunosorbent assay (ELISA).ResultsThe B7-H3 haplotype T-A-C-T was less frequently observed in T1D patients compared to the controls (OR: 0.31, 95% CI: 0.16–0.61). B7-H3 expression on monocytes showed significant upregulation in T1D patients and was positively correlated with several clinical features including ALT, fast C-peptide 120 min, HbAlc, IFN-γ, IL-6 and TNF-α (P < 0.05). The concentration of sB7-H3 in serum increased in T1D patients (P < 0.0001). We also observed that B7-H3-T-A-C-T was associated with the decreased release of sB7-H3 but not the membrane form.ConclusionsB7-H3 may act as a potential biomarker related to the pathogenesis of T1D. The B7-H3-T-A-C-T polymorphism variant is associated with the low risk of T1D as well as less release of sB7-H3.

Association of APOB and LIPC polymorphisms with type 2 diabetes in Chinese Han population

BackgroundApolipoprotein B (APOB), and hepatic lipase (LIPC) genes have been shown to play a key role in lipid metabolism in type 2 diabetes (T2D). This study aimed to investigate the association of the three polymorphisms (rs679899 in APOB and rs6078 and rs6083 in LIPC) with T2D and related clinical quantitative traits. MethodsWe conducted a case-control study in Chinese Han population, with a total of 929 T2D patients and 1044 healthy subjects in Chinese Han population. Polymorphisms were genotyped by MassARRAY Genotyping System. ResultsThe risk allele G of the polymorphism rs679899 was related to T2D (odds ratio (OR): 1.207, 95% confidence interval (CL): 1.006–1.448, P = 0.043) and the polymorphism rs679899 was associated with glutamyl transpeptidase (GGT) levels (P = 0.001). We also showed that the polymorphism rs6083 was associated with cholesterol (CHOL) levels (P = 0.012), triglyceride (TG) levels (P = 0.040), and low-density lipoprotein cholesterol (LDL) levels (P = 0.033). No significant difference in genotypic frequencies of rs6078 and rs6083 was observed between T2D patients and controls. ConclusionThis study suggests that the APOB polymorphism rs679899 is associated with type 2 diabetes and GGT levels, while the LIPC polymorphism rs6083 may influence CHOL, TG, and LDL levels in Chinese Han population.

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.

Relationship between SLC22A1 and SLC22A4 gene polymorphisms and risks of type 2 diabetes in Chinese Han population

Objective: This study was conducted to investigate the relationship between SLC22A1 and SLC22A4 gene polymorphisms and genetic susceptibility to type 2 diabetes in Chinese Han population. Methods: The research group comprised 110 patients with type 2 diabetes in Chinese Han population, while and the control group consisted of 110 healthy volunteers. The polymorphisms of SLC22A1 gene rs628031 and rs2282143 loci and SLC22A4 gene rs2073838 and rs272893 loci were detected in the subjects in the two groups. Genotype distributions and allele frequencies of the two genes were compared between the research and control groups. Results: Statistically significant differences were identified in the genotype distributions of SLC22A1 gene rs628031 and rs2282143 loci between the research and control groups (P 0.05). However, the genotype distributions of rs272893 locus showed a significant difference between the research and control groups (P<0.05). Conclusion: The polymorphisms of SLC22A1 gene rs628031 and rs2282143 loci and SLC22A4 gene rs272893 locus of patients with type 2 diabetes indicated a significant difference between the research and control groups, thereby suggesting that these genetic locus mutations increase the risk in patients with type 2 diabetes in Chinese Han population.

Relationship Between SLC22A1 and SLC22A4 Gene Polymorphisms and Risk of Type 2 Diabetes in Chinese Han Population.

This study was to investigate the relationship between SLC22A1 and SLC22A4 gene polymorphisms and genetic susceptibility to type 2 diabetes in Chinese Han population. The research group comprised 110 Chinese Han patients with type 2 diabetes, and the control group included 110 healthy volunteers. The polymorphisms of SLC22A1 gene rs628031 and rs2282143 loci and SLC22A4 gene rs2073838 and rs272893 loci were detected in the two groups. Statistically significant differences were identified in the genotype distributions of SLC22A1 gene rs628031 and rs2282143 loci between the two groups (p < 0.05). The A allele frequency of SLC22A1 gene rs628031 locus and the T allele frequency of rs2282143 locus were higher in the research group than in the control group (p < 0.05). The genotype distributions of rs272893 locus showed a significant difference between the two groups (p < 0.05), but not SLC22A4 gene rs2073838 locus (p > 0.05). The polymorphisms of SLC22A1 gene rs628031 and rs2282143 loci and SLC22A4 gene rs272893 locus of patients with type 2 diabetes indicated a significant difference between the two groups, suggesting that these genetic locus mutations increase the risk of type 2 diabetes in Chinese Han patients.

Rs290487 of TCF7L2 Gene is not Associated with Type 2 Diabetes in Chinese Han Population: a Case Control Study and Meta-analysis

rs290487 in TCF7L2 was originally identified to be associated with type 2 diabetes in Taiwan Chinese population. However, discrepancies were noted in subsequent replicated studies. So the aim of this study is to investigate the effect of rs290487 in TCF7L2 on genetic susceptibility of type 2 diabetes in a large sample of Chinese -population. In meta analysis of 9 studies with 9 422 cases and 8 585 control subjects, no association was found between rs290487 and type 2 diabetes in China (OR=1.06, 95% confidence interval (CI), 0.96-1.17, p=0.19). In case control study, rs290487 was genotyped in 5 151 diabetic patients and 4 650 non-diabetic controls. After adjusting for sex, age and BMI, and using an additive genetic model, logistic regression analysis revealed no association between rs290487 and type 2 diabetes (OR=1.015, 95%CI 0.949-1.087, p=0.662). No association was found between rs290487 and type 2 diabetes in northern and southern Chinese population separately. In summary, we have found no association between rs290487 and type 2 diabetes in Chinese population. This SNP is unlikely an influential genetic variant with type 2 diabetes in Chinese population.

The association between gene polymorphism of TCF7L2 and type 2 diabetes in Chinese Han population: a meta-analysis.

In recent years, it has been widely accepted that transcription factor 7-like 2 (TCF7L2) is associated with type 2 diabetes mellitus (T2DM) in multiple ethnic groups, especially its single nucleotide polymorphisms of rs7903146C/T, rs12255372G/T and rs290487T/C. However, the results previously obtained in Chinese Han population are often inconsistent. For clearing this issue, herein we performed meta-analysis based on the reports that can be found to assess the association. In the meta-analysis, Odds ratio (OR) and 95% confidence interval (95% CI) were calculated with random-effect model or fixed-effect model based on the heterogeneity analysis. The quality of included studies was evaluated by using the Newcastle-Ottawa Scale. The sensitivity analysis was used to confirm the reliability and stability of the meta-analysis. In total, 20 case-control studies with 9122 cases of T2DM and 8017 controls were included. Among these case-control studies, we selected 13 ones on rs7903146 C/T, 5 ones on rs12255372 G/T, 8 ones on rs290487 T/C. The results indicated that rs7903146C/T polymorphism was significantly associated with T2DM (T vs. C, OR = 1.73, 95% CI = 1.39–2.16). There was no evidence that rs12255372G/T and rs290487T/C polymorphisms increased T2DM risk (T vs. G, OR = 1.77, 95% CI = 0.88–3.56; C vs. T, OR = 1.08, 95% CI = 0.93–1.25). Subgroup analysis of different regions proved the relationship between rs7903146C/T polymorphism and T2DM risk in both the northern and the southern China. The association of rs290487 with T2DM was affected by body mass index, whereas the association of rs7903146 and rs290487 with T2DM was influenced neither by age nor by sex. In conclusion, this study indicated that the rs7903146C/T polymorphism of the TCF7L2 gene had a significant effect on T2DM risk in Chinese Han population, with rs12255372G/T and rs290487T/C polymorphisms showing no significant effect.

Association of the G-250A promoter polymorphism in the hepatic lipase gene with the risk of type 2 diabetes mellitus

ObjectiveVariants in hepatic lipase (HL) gene which is a lipolytic enzyme involved in the metabolism of plasma lipoprotein and regulating lipid and lipoprotein metabolism are potential candidate genes for type 2 diabetes. Association of the polymorphisms in the promoter region of the HL gene (LIPC) to the plasma HDL-C concentration has been investigated. In this study, we investigated whether the G-250A polymorphism of LIPC is associated with type 2 diabetes in Chinese Han population. Subjects and methodsA total of 130 patients with type 2 diabetes and 133 healthy subjects as control were randomly selected from January 2008 to January 2011 in endocrine wards of Zhengzhou People's Hospital. The G-250A polymorphisms were studied by polymerase chain reaction and restriction fragment length polymorphism. A logistic regression analysis was performed to determine the association between the rare allele and type 2 diabetes mellitus. ResultsThe frequency of the -250A allele was 0.297 in the T2DM group and 0.388 in the control group (P<0.05), with the difference remaining significant. ConclusionsPatients who are carrying of the -250A allele in the promoter of the LIPC gene are susceptible to type 2 diabetes mellitus in Chinese Han population.

Meta-analysis of association studies between five candidate genes and type 2 diabetes in Chinese Han population

The multiple small-scale association studies of candidate genes for type 2 diabetes mellitus in the Chinese Han population have shown inconsistent results. Here, we performed a meta-analysis to evaluate the contribution of five candidate genes to the pathogenesis of type 2 diabetes in the Chinese Han population. We searched for relevant published papers and used STATA v.11.0 to perform a meta-analysis on six single-nucleotide polymorphisms in five genes-ADIPOQ-rs2241766 (SNP45) and -rs1501299 (SNP276), ADRB3-rs4994 (Trp64Arg), CAPN10-rs3792267 (SNP43), ENPP1-rs1044498 (K121Q), and PPARGC1A-rs8192678 (Gly482Ser)-in the Chinese Han population under an additive genetic model. The pooled odds ratios (95% confidence intervals and P-values) were 0.71 (0.60-0.83; P < 0.001) for ADIPOQ-rs2241766, 0.79 (0.64-0.97; P = 0.027) for ADIPOQ-rs1501299, 1.27 (1.07-1.51; P = 0.006) for ADRB3-rs4994, 0.79 (0.57-1.10; P = 0.163) for CAPN10-rs3792267, 1.41 (1.13-1.76; P = 0.003) for ENPP1-rs1044498, and 1.54 (1.34-1.81; P < 0.001) for PPARGC1A-rs8192678. There was high heterogeneity for ADIPOQ-rs2241766, ADIPOQ-rs1501299, and CAPN10-rs3792267 (I² = 74.9, 69.4, and 75.8%, respectively), but not for ADRB3-rs4994, ENPP1-rs1044498, and PPARGC1A-rs8192678 (I² = 0.0, 43.4, and 23.3%, respectively). Under an additive genetic model, the C allele of ADRB3-rs4994, the C allele of ENPP1-rs1044498, and the A allele of PPARGC1A-rs8192678 increase the risk of type 2 diabetes in the Chinese Han population.

Killer cell immunoglobulin‐like receptor along with HLA‐C ligand genes are associated with type 1 diabetes in Chinese Han population

Killer cell immunoglobulin-like receptor (KIR) genes and their putative ligands human leukocyte antigen (HLA)-C genes have been associated with type 1 diabetes (T1D). We hypothesize that KIR genes and their ligands HLA-C genes are important in T1D aetiology. KIR and HLA-C ligand genotyping was performed in 259 T1D patients and 262 healthy children. No significant difference was observed in the distribution of KIR genes between T1D patients and healthy controls. However, frequency of HLA-C1 gene and HLA-C2 gene (marginal association) was higher in patient group. The combinations 2DL2-/HLA-C1+; 2DL3+/HLA-C1+; 2DS2-/HLAC1+ were positively associated with T1D. The combinations 2DL1+/HLA-C2-; 2DL2-/HLA-C1-; 2DL3+/HLA-C1-; 2DS2-/HLAC1- were found to be negatively associated with T1D. Among the genes we tested, a combination of HLA-C1 and -C2 conferred the strongest association with T1D and the strength of this association was higher than that of HLA-C1 alone. The frequencies of KIR 2DL1, 2DL2 and 2DL3 and HLA-C1 were higher in T1D patients positive for GAD65 autoantibody; frequency of KIR 2DS4 is higher in T1D patients positive for IA-2 autoantibody. The association between KIR/HLA-C gene and autoantibody status was not statistically significant after applying Bonferroni correction. In our study of a Han population (East China), we found no direct association of KIR genes with T1D. However, a combination of HLA-C1 and -C2 showed a positive association with T1D. Different combinations of HLA-C and KIR showed positive and negative association with T1D.

Association between polymorphisms in RAPGEF1, TP53, NRF1 and type 2 diabetes in Chinese Han population

Type 2 diabetes is a common complex disorder with environmental and genetic components. The aim of the present study was to investigate the association between the polymorphisms of RAPGEF1, TP53 and NRF1 and the risk of type 2 diabetes in the Chinese Han population. We genotyped rs11243444 ( RAPGEF1), rs1042522 ( TP53) and rs1882095 ( NRF1) in a case-control study, including 273 type 2 diabetes and 247 healthy controls. A significant association was found in a variant of TP53 (rs1042522, odd ratio (OR) = 1.28, 95% confidence interval (CI) = 1.00–1.64; P = 0.046), whereas polymorphisms in RAPGEF1, NRF1 were not associated with the risk of type 2 diabetes. Furthermore, a potential gene–gene interaction showed the odds of being affected with type 2 diabetes was 2.54 times greater in subjects with the TP53 (rs1042522) and RAPGEF1 (rs11243444) risk alleles than those without either (95% CI = 1.34–4.81; P = 0.004) and the NRF1 gene polymorphism reached significance when paired with TP53:(OR = 3.87, 95% CI = 1.87–8.40; P = 0.0006). We demonstrated that the polymorphism in TP53 (rs1042522) was associated with type 2 diabetes, and that potential interaction of TP53 (rs1042522) and RAPGEF1 (rs11243444), or NRF1 (rs1882095) increased the risk of type 2 diabetes.

No association of vascular endothelial growth factor A gene rs9369425 polymorphism with glucose metabolism in Chinese Han population

To investigate the relationship between the vascular endothelial growth factor A gene (VEGFA) rs9369425 single nucleotide polymorphism (SNP) and type 2 diabetes in Chinese Han population. One thousand eight hundred and ninety two type 2 diabetes patients and 1808 controls with normal glucose were recruited in this study. Phenotypes including body mass index, waist, waist hip ratio, plasma glucose and serum insulin levels of blood obtained both at 0 and 120 minute during standard 75-gram glucose oral glucose tolerance tests, were analyzed. Insulin resistance and beta cell function were assessed by homeostasis model assessment (HOMA-IR and HOMA-B). Genotyping was performed by time-of-light mass spectrum using a Sequenom platform. The frequencies of minor allele G in the diabetic patients and controls were 10.8% and 11.3% respectively. No significant difference of allele distribution was detected between the cases and controls (P=0.5086). No significant difference (P>0.05) was detected on the association between rs9369425 SNP and clinical phenotypes. VEGFA rs9369425 was not associated with type 2 diabetes in Chinese Han population. Whether there is association in any other loci in this gene remained to be investigated.

PAX4 gene polymorphism and islet autoantibody-negative ketosis-prone diabetes

To investigate PAX4 gene polymorphism and its association with islet autoantibody-negative patients with ketosis-prone diabetes in Chinese Han population. We screened the variation of exon 3 and 9 within PAX4 gene by denaturing high performance liquid chromatography(DHPLC) in 112 non-diabetes control subjects (NC group) and 141 patients with ketosis-prone diabetes (KPD group), who were both negative for glutamic acid decarboxylase antibody (GAD-Ab) as well as protein tyrosine phosphatase antibody (IA-2Ab). The sequences of abnormal peaks were analyzed by DNA-sequencing. The A1168C single nucleotide polymorphism in PAX4 gene was genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 308 non-diabetic control subjects and 141 KPD patients. No variation was discovered in PAX4 gene exon 3 both in the patients and in the controls. There was a single nucleotide polymorphism locus A1168C in the PAX4 gene exon 9, which induced missence mutation P321H (rs712701). No significant difference was observed in the genotype and allele frequencies of A1168C polymorphism between KPD patients and control subjects (P=0.532, 0.426). The difference was detected in the CC genotype and C allele frequencies in the KPD group when patients were stratified by gender (P=0.009,0.028). According to age at diagnosis, the difference was observed in the CC genotype and C allele frequencies between <20 years old and > or = 20 years old in the KPD group (P=0.034,0.032). The level of FCP in the CC genotype group was significantly higher than that of FCP in AA genotype group (P=0.005). A1168C polymorphism in PAX4 gene may not play an essential role in the genetic susceptibility of the islet autoantibody-negative KPD in Chinese Han population. However, A1168C variation may contribute to the predisposition to the male or < 20 years old patients with islet autoantibody-negative KPD.

Association of polymorphisms in transcription factor 7-like 2(TCF7L2) gene with type 2 diabetes in Chinese Han population

Objective To study the association of transcription factor 7-like 2(TCF7L2)polymorphisms with tvpe 2 diabetes mellitus in Chinese Han population. Methods Two polymorphisms (rs7903146 and rs12255372)of TCF7L2 gene were genotyped in 446 patients with type 2 diabetes mellitus(T2DM group)and 303 normal subiects (NC group) by PCR-restriction fragment length polymorphism(PCR-RFLP).Waist circumference.body mass index,plasma glucose,serum insulin,lipid profiles,high-sensitivity C-reactive protein and non-esterified fatty acid were measured.Homeostasis model assessment of insulin resistance(HOMA-IR)and β-cell function(HOMA-β)were calculated.Results (1) In T2DM group,T allele frequency and CT,TY geno tvpe frequeneies of rs7903146 were significantly higher than those in NC group(0.093,0.150,0.018 vs 0.043, 0.079,0.003,respectively,a11 P<O.O 1).Logistic regression analysis showed that the CT/TT genotype was a risk factor of tvpe 2 diabetes(OR=2.25,95%CI 1.39-3.62,P=0.001)and was associated with the decrease of insulin secretion. (2) No significant association was observed in vs12255372 alleles and genotypes with type 2 diabetes mellitus.Conclusion These results indicate that TCF7L2 might be one of the candidate genes for confe ring susceptibi lity to type 2 diabetes mellitus in the Chinese Han population. Key words: Polymorphism,single nucleotide; TCF7L2 gene; Diabetes mellitus,type 2; Association study

Association study between &lt;I&gt;PPARGC1A&lt;/I&gt; Thr394Thr/ Gly482Ser polymorphisms and type 2 diabetes

To investigate the association between single nucleotide polymorphisms (SNPs) rs2970847(Thr394Thr) and rs8192678(Gly482Ser) of peroxisome proliferators activated receptor gamma coactivator-1(PPARGC1A)gene and type 2 diabetes in Chinese Han population in Hubei. The Thr394Thr and Gly482Ser polymorphisms of the PPARGC1A gene were genotyped in 307 controls and 344 type 2 diabetes patients. Single marker/haplotype association analyses and logistic re-gression analysis were performed. Significant differences in genotypic and allelic frequencies were observed between cases and controls for the Thr394Thr polymorphism (genotype, P=0.006; allele, Plt;0.001). The genotype AA of the Thr394Thr polymorphism and the haplotype Thr394(ACA)- Ser482 were significantly associated with type 2 diabetes. No differences in the genotypic and allelic frequencies between cases and controls were found for the Gly482Ser polymorphism. PPARGC1A is a susceptibility gene for type 2 diabetes in Chinese Han population in Hubei.

Novel Mutations of Mitochondrial DNA Associated with Type 2 Diabetes in Chinese Han Population

Mitochondrial single nucleotide polymorphisms (mtSNPs) have been reported to associate with type-2 diabetes mellitus (T2DM), but mtSNPs appear to be considerably different among different populations and regions. To determine mtSNPs in Chinese Han patients with T2DM, the entire sequences of the mitochondrial genomes from 72 T2DM Chinese (59 +/- 4 years) and 50 age-matched healthy subjects (controls) in Chongqing region of Western China were directly sequenced and mtSNPs were analyzed. We found that M8, M9, D, G, R and A haplogroups exist in Chinese Han population and the frequency of haplogroup M9 was significantly higher in patients with T2DM than in the controls (p = 0.0006, OR 0.06 [95% CI 0.008-0.476]). MtSNPs T3394C in NADH dehydrogenase subunit 1 (ND1), G4491A in ND2, T16189C and T16519C were found with significantly higher frequency in patients with T2DM than in the controls (T16189C, p = 0.0045; T16519C, p < 0.0001; T3394C, p = 0.0015; G4491A, p = 0.0015). In contrast, the frequency of C5178A in ND2 and A10398G in ND3 was higher in the controls than in patients with T2DM (C5178A, p = 0.014; A10398G, p = 0.0011). Our results indicate that mtSNPs T3394C, G4491A, T16189C and T16519C show susceptible tendency to T2DM and mtSNPs C5178A and A10398G seem to be genetic factors for against T2DM. These mtSNPs determined in our study is useful and could be used for early diagnosis and prevention of T2DM in Chinese Han population.

Correlation of CD40 gene polymorphisms with acute coronary syndrome, hypertension and diabetes

To investigate the correlation of CD40-E1SNP (-1C/T) and CD40-E4SNP with acute coronary syndrome (ACS), hypertension and diabetes in Chinese Han population. The allele frequencies of CD40-E1SNP (-1C/T) and CD40-E4SNP were assayed by polymerase chain reaction-restriction fragment length polymorphism and DNA sequence technology in 160 definite ACS patients and 92 controls with negatively coronary arteriography. Multivariate logistic regression models were used to analyzed the interaction between the CD40 gene polymorphisms and hypertension and diabetes. CD40-1C allele frequency of the ACS group was 0.606, significantly higher than that of the control group (0.489, P < 0.01), while the T allele frequency of the ACS group was 0.394, significantly lower than that of the control group (0.511, P < 0.01). The frequency of CC genotype was much higher in the ACS group than in the control group (P < 0.01). C allele increased the risk of ACS (OR = 1.608, 95% CI: 1.12 - 2.32, P = 0.011). After adjustment of confounding variables, such as age, sex, and body mass index, the binary logistic analysis showed a significant gene-environment interaction (P < 0.05). The OR value were: 1.608 for C allele (95% CI: 1.12 - 2.32, P < 0.05), 5.71 for C allele-with hypertension (95% CI: 1.12 - 29.08, P < 0.05), 1.44 for C allele-without diabetes (95% CI: 1.12 - 5.13, P < 0.01), and 2.35 for C allele-with diabetes (95% CI: 1.47 - 4.82, P < 0.01). Expression of CD40-E4SNP was not found in these subjects. CD40-1C/T polymorphism is associated with ACS in Chinese people. The -1C allele carriers have higher risk of ACS if they get hypertension or diabetes; CD40-E4SNP may not exist in Chinese people.

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.