Jingjie Li

Impact of diabetes-related gene polymorphisms on the clinical characteristics of type 2 diabetes Chinese Han population

We investigated the correlation between type 2 diabetes (T2D)-related genes and the clinical characteristics of T2D in the Chinese Han population. Our study included 319 patients and 387 controls. Age, gender, clinical features, medications intake and biochemical blood profiles were analyzed. Genotyping was performed on a total of 18 single nucleotide polymorphisms previously reported to be associated with T2D. Our analyses revealed that the CT genotype of ARHGAP22 rs4838605 is associated with T2D risk. Upon analyzing the subjects’ clinical characteristics, we found that for rs2811893, the TT genotype correlated with high creatinine levels, while the AA genotype of rs17045754 and the TT genotype of rs4838605 correlated with elevated triglyceride levels. In addition, the AA genotype of rs17376456 and the TT genotype of rs6214 (p = 0.006) correlated with elevated hemoglobin A1c levels. Lastly, those carrying the TT genotype of rs7772697 and the CA genotype of rs3918227 exhibited higher mean body mass index and Cystatin C than controls. Our results showing that the ARHGAP22 gene is associated with an increased risk of T2D, and that seven SNPs in MYSM1, PLXDC2, ARHGAP22 and HS6ST3 promote T2D progression and could help predict the clinical course of T2D in patients at risk.

Polymorphisms of the TCF4 gene are associated with the risk of schizophrenia in the Han Chinese

Schizophrenia (SCZ) is a complex and severe mental disorder with highly heritability (80%). Several large genome‐wide association studies have identified that the transcription factor 4 (TCF4) polymorphisms were strongly associated with SCZ. Therefore, the present study was to replicate the potential relationships between the TCF4 polymorphisms and SCZ. Furthermore, the study also investigated whether other variants were associated with SCZ in the Han Chinese. We conducted a case‐control study including 499 patients and 500 healthy controls. Five SNPs were successfully genotyped and evaluated the association with SCZ by using χ2 test and genetic model analysis. We found that the genotype “AG” of rs9320010 and “GA” of rs7235757 decreased SCZ risk (OR = 0.70, 95%CI = 0.50–0.99, P = 0.041; OR = 0.69, 95%CI = 0.49–0.97, P = 0.034, respectively). In the genetic model analysis, we also observed that the allele “A” of rs9320010 and “G” of rs7235757 were inversely related with the risk of SCZ in the dominant model (OR = 0.72, 95%CI = 0.52–0.98, P = 0.039; OR = 0.69, 95%CI = 0.50–0.96, P = 0.025, respectively). Further interaction and stratification analysis suggested that rs1452787 was notably correlated with increased SCZ risk in males (OR = 2.77, 95%CI = 1.43–5.35, P = 0.002). Our study indicated that rs9320010, rs7235757, and rs1452787 were prominently associated with SCZ. Further studies are required to verify our findings and focus on determining the biological functions of the SNPs.

Genetic polymorphisms of the drug-metabolizing enzyme cytochrome P450 3A5 in a Uyghur Chinese population.

Abstract 1.  Detection of CYP3A5 variant alleles, and knowledge about their allelic frequency in Uyghur ethnic groups, is important to establish the clinical relevance of screening for these polymorphisms to optimize pharmacotherapy. 2. We used DNA sequencing to investigate the promoter, exons and surrounding introns, and 3′-untranslated region of the CYP3A5 gene in 96 unrelated healthy Uyghur individuals. We also used SIFT and PolyPhen-2 to predict the protein function of the novel non-synonymous mutation in CYP3A5 coding regions. 3. We found 24 different CYP3A5 polymorphisms in the Uyghur population, three of which were novel: the synonymous mutation 43C > T in exon 1, two mutations 32120C > G and 32245T > C in 3′-untranslated region, and we detected the allele frequencies of CYP3A5*1 and *3 as 64.58% and 35.42%, respectively. While no subjects with CYP3A5*6 were identified. Other identified genotypes included the heterozygous genotype 1A/3A (59.38%) and 1A/3E (11.46%), which lead to decreased enzyme activity. In addition, the frequency of haplotype “TTAGGT” was the most prevalent with 0.781. 4. Our data provide new information regarding CYP3A5 genetic polymorphisms in Uyghur individuals, which may help to improve individualization of drug therapy and offer a preliminary basis for more rational use of drugs.

CDKN2BAS polymorphisms are associated with coronary heart disease risk a Han Chinese population

The goal of our study was to determine whether CDKN2BAS polymorphisms are associated with coronary heart disease (CHD) risk in a Han Chinese population. Eight SNPs were genotyped in 676 men and 465 women. We used χ2 tests and genetic model analyses to evaluate associations between the SNPs and CHD risk. We found that rs10757274 was associated with an increased risk of CHD in both men (allele G: Odds ratio [OR] = 1.30, 95% confidence interval [CI]: 1.05-1.61, P = 0.018; codominant model: P = 0.042; recessive model: OR = 1.70, 95% CI: 1.10-2.62, P = 0.016; log-additive model: OR = 1.34, 95% CI: 1.05-1.71, P = 0.019) and women (dominant model: OR = 2.26, 95% CI: 1.28-3.99, P = 0.004). In addition, rs7865618 was associated with an 8.10-fold increased risk of CHD in women under a recessive model (OR = 8.10, 95% CI: 1.74-37.68, P = 0.006). Interestingly, the haplotype AA (rs10757274 and rs1333042) of CDKN2BAS was associated with decreased the risk of CHD in men (OR = 0.72, 95% CI: 0.55 - 0.95, P = 0.022).

Correlation between polymorphisms in microRNA-regulated genes and cervical cancer susceptibility in a Xinjiang Uygur population

We explored the correlation between single nucleotide polymorphisms (SNPs) and susceptibility to cervical cancer (CC) in a Xinjiang Uygur population. Ten SNPs in eight miRNA-regulated genes were selected for analysis. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using unconditional logistic regression analysis. Multivariate logistic regression analysis was used to detect correlations between SNPs and CC. We found that minor allele “C” of rs512715 in NEAT1 was associated with an increased risk of CC in the allele, codominant, dominant, overdominant and log-additive models. Minor allele “C” of rs4777498 in CELF6 was associated with an increased risk of CC in the recessive model. Minor allele “C” of rs3094 in RNASE4 was associated with increased risk of CC in the allele, dominant and log-additive models. In clinical stage III/IV CC patients, minor allele “C” of rs3094 in RNASE4 and minor allele “C” of rs8004334 in JDP2 were associated with increased risk. In subtype squamous carcinoma CC patients, minor allele “C” of rs512715 in NEAT1 and minor allele “C” of rs3094 in RNASE4 were associated with increased risk. In subtype adenocarcinoma CC patients, minor allele “C” of rs3094 in RNASE was associated with increased risk.

A case-control study of the association between the EGFR gene and glioma risk in a Chinese Han population

The Epidermal Growth Factor Receptor gene has been reported to be involved in the progression of gliomas which is one of the deadliest primary brain tumors in humans. To determine potential association between EGFR and glioma risk, we performed a case-control study with 394 glioma patients and 298 cancer-free controls in which captured a total of 8 tag single nucleotide polymorphisms of EGFR gene from Xi’an, China. SPSS 19.0 statistical packages, χ2 test, genetic model analysis and SHEsis software platform were analyzed s the variants in EGFR gene associations with glioma risk. For five different inheritance models analyzed, the following genotypes were associated with increased glioma risk. In the codominant model, genotype CC (rs730437, OR = 1.93, p = 0.024; rs1468727, OR = 2.02, p = 0.007); In the dominant model, genotype CA and CC (rs730437, OR = 1.45, p = 0.026), genotype GA and AA (rs845552, OR = 1.40, p = 0.044); In the recessive model, genotype CC (rs730437, OR = 1.64, p = 0.026; rs1468727, OR = 1.87, p = 0.002); In the additive model, genotype CC (rs730437, OR = 1.32, p = 0.006; rs1468727, OR = 1.39, p = 0.005), genotype GG (rs11506105, OR = 1.32, p = 0.02) and genotype AA (rs845552, OR = 1.27, p = 0.04). Our study indicated that 8 mutants located in EGFR gene were risk-conferring factors, larger and different populations with EGFR polymorphisms are required to verify these associations.

Association between TNIP1, MPHOSPH6 and ZNF208 genetic polymorphisms and the coronary artery disease risk in Chinese Han population

Introduction Coronary artery disease (CAD) is a common disease and among the leading cause of death in the general population. Inherited factors are involved in the pathogenesis of CAD. Aims Our study examined whether SNPs in TNIP1, MPHOSPH6, ZNF208 to be associated with CAD risk in a Chinese Han population. We recruited 596 CAD patients, 603 controls and genotyping fifteen SNPs using Sequenom MassARRAY. For association analysis between TNIP1, MPHOSPH6 and ZNF208 and CAD was determined by Odds ratios (ORs) with 95% confidence intervals (CIs) using Logistic Regression. Results The results indicated in allel model, the rs960709 in TNIP1 was associated with CAD risk (OR = 0.78, 95%CI = 0.65-0.94, P=0.010). The genetic model results showed that the rs960709 (A/G) polymorphism was associated with the risk of developing CAD in codominant, Dominant and Log-additive. The rs1056654 A/A allele and CAD patients compared to the healthy controls in recessive model (OR = 0.55, 95%CI = 0.34-0.90; P = 0.018). We also found that three SNPS in ZNF208 associated with CAD, respectively, rs2188971, rs8103163 and rs7248488. Linkage disequilibrium (LD) and haplotype analyses of the SNPs found that the CTA haplotype (rs1056675, rs1056654, rs11859599) and rs2188972A/rs2188971T/rs8103163A/rs7248488A (ATAA) were associated with CAD. Conclusion In conclusion, the present study provided evidence that SNPs in the TNIP1, ZNF208 and MPHOSPH6 were associated with CAD in Chinese Han population. It is possible that these SNPs are CAD risk factors and these data can provide.

Association between single nucleotide polymorphisms in the TSPYL6 gene and breast cancer susceptibility in the Han Chinese population

We investigated the associations between single nucleotide polymorphisms (SNPs) in the testis-specific Y-encoded-like protein 6 (TSPYL6) gene and breast cancer (BC) susceptibility in the Han Chinese population. A total of 183 BC patients and 195 healthy women were included in the study. Six SNPs in TSPYL6 were genotyped and the association with BC risk analyzed. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using unconditional logistic regression analysis. Multivariate logistic regression analysis was used to identify SNPs that correlated with BC susceptibility. Rs11896604 was associated with a decreased risk of BC based on dominant and genotype models. Rs843706 was associated with an increased risk of BC based on a recessive model. Rs11125529 was associated with decreased BC susceptibility based on a genotype model. Finally, rs843711 inversely correlated with clinical stage III/IV BC. Our findings reveal a significant association between SNPs in the TSPYL6 gene and BC risk in a Han Chinese population.

Effect of epidermal growth factor receptor gene polymorphisms on prognosis in glioma patients

Previous studies suggested that single nucleotide polymorphisms (SNPs) in epidermal growth factor receptor (EGFR) are associated with risk of glioma. However, the associations between these SNPs and glioma patient prognosis have not yet been fully investigated. Therefore, the present study was aimed to evaluate the effects of EGFR polymorphisms on the glioma patient prognosis. We retrospectively evaluated 269 glioma patients and investigated associations between EGFR SNPs and patient prognosis using Cox proportional hazard models and Kaplan-Meier curves. Univariate analysis revealed that age, gross-total resection and chemotherapy were associated with the prognosis of glioma patients (p < 0.05). In addition, four EGFR SNPs (rs11506105, rs3752651, rs1468727 and rs845552) correlated with overall survival (OS) (Log-rank p = 0.011, 0.020, 0.008, and 0.009, respectively) and progression-free survival PFS (Log-rank p = 0.026, 0.024, 0.019 and 0.009, respectively). Multivariate analysis indicated that the rs11506105 G/G genotype, the rs3752651 and rs1468727 C/C genotype and the rs845552 A/A genotype correlated inversely with OS and PFS. In addition, OS among patients with the rs730437 C/C genotype (p = 0.030) was significantly lower OS than among patients with A/A genotype. These data suggest that five EGFR SNPs (rs11506105, rs3752651, rs1468727, rs845552 and rs730437) correlated with glioma patient prognosis, and should be furthered validated in studies of ethnically diverse patients.

Association of TERT polymorphisms with chronic hepatitis B in a Chinese Han population

In this study, we investigated the association between the polymorphisms of telomerase reverse transcriptase (TERT) gene and the risk of chronic hepatitis B (CHB) in a Chinese Han population. Four single nucleotide polymorphisms (SNPs) in TERT (rs10069690, rs2242652, rs2853677 and rs2853676) were genotyped from 224 CHB patients and 300 healthy controls using the Sequenom Mass-ARRAY platform. We used genetic model, haplotype analyses, chi-square test, logistic regression analysis to evaluate the association between SNPs and CHB risk. The relative risk was estimated by odd ratios (ORs) and 95% confidence intervals (CIs). We found that rs10069690 was significantly associated with an increased CHB risk in the dominant model (adjusted OR = 1.70, 95% CI: 1.06–2.71, P = 0.031) and additive model (adjusted OR = 1.62, 95% CI: 1.09–2.41, P = 0.018). The haplotype “TA” (rs10069690 and rs2242652) was found to be associated with an increased risk of CHB (adjusted OR = 1.58, 95% CI: 1.05–2.38, P = 0.027). Our results suggested potential genetic contributes for TERT in CHB development in a Chinese Han population. Future functional and association studies with larger sample sizes are required to confirm these findings.