Southeastern Chinese Population Research Articles

Association of lipoprotein lipase (LPL) gene variants with hyperlipidemic acute pancreatitis in southeastern Chinese population.

The study aims to explore the relationship between lipoprotein lipase (LPL) variants and hyperlipidemic acute pancreatitis (HLAP) in the southeastern Chinese population. In total, 80 participants were involved in this study (54 patients with HLAP and 26 controls). All coding regions and intron-exon boundaries of the LPL gene were sequenced. The correlations between variants and phenotypes were also analysed. The rate of rare LPL variants in the HLAP group is 14.81% (8 of 54), higher than in controls. Among the detected four variants (rs3735959, rs371282890, rs761886494 and rs761265900), the most common variant was rs371282890. Further analysis demonstrated that subjects with rs371282890 "GC" genotype had a 2.843-fold higher risk for HLAP (odds ratio [OR]: 2.843, 95% confidence interval [CI]: 1.119-7.225, p = 0.028) than subjects with the "CC" genotype. After adjusting for sex, the association remained significant (adjusted OR: 3.083, 95% CI: 1.208-7.869, p = 0.018). Subjects with rs371282890 "GC" genotype also exhibited significantly elevated total cholesterol, triglyceride and non-high-density lipoprotein cholesterol levels in all the participants and the HLAP group (p < 0.05). Detecting rare variants in LPL might be valuable for identifying higher-risk patients with HLAP and guiding future individualised therapeutic strategies.

Association of BST1 polymorphism with idiopathic restless legs syndrome in Chinese population.

Parkinson's disease (PD) and restless legs syndrome/Willis-Ekbom disease (RLS/WED) are both common movement disorders. Based on their clinical overlap, association studies of PD and RLS/WED have been conducted for many years. To investigate whether or not the genetic risk factor of PD was also associated with RLS/WED. We included 102 idiopathic RLS/WED patients and 189 matched controls from southeast China. The clinical data included the International Restless Legs Syndrome Study Group Rating Scale, the subtypes of RLS/WED symptoms (painful or other discomfort), the comorbidities, the pregnancy history of female patients, the Hamilton Depression Scale (HAMD), and the Pittsburgh Sleep Quality Index (PSQI) questionnaire. Risk gene analysis between RLS/WED and control groups including 21 SNPs (single nucleotide polymorphisms) was conducted. Genotyping was done by Sanger sequencing. We found that rs4273468 polymorphism of BST1 gene increased the risk of idiopathic RLS/WED patients in southeastern Chinese population (P = <0.001, OR = 2.85, p = 0.019 after Bonferroni correction). Moreover, the haplotype of G-G (rs4698412-rs4273468) was significantly associated with Chinese RLS/WED patients (p = <0.001). BST1 may contribute to the development of RLS/WED. Further studies on larger cohorts are needed to confirm these findings.

BRD4 and PIN1 gene polymorphisms are associated with high pulse pressure risk in a southeastern Chinese population

BackgroundBRD4 and PIN1 have been described to be involved in inflammation and vascular endothelial cell dysfunction, which in turn may increase pulse pressure.HypothesisGenetic mutations within the BRD4 and PIN1 genes could affect the risk of high pulse pressure.MethodsA total of four single nucleotide polymorphisms (SNPs) (BRD4: rs4808278; PIN1: rs2233678, rs2287838, and rs2233682) were genotyped in a cohort of 666 hypertensive patients and 232 normotensive controls with Chinese Han origin. Generalized multifactor dimensionality reduction (GMDR) was used to screen the best interaction combination among the four SNPs within the BRD4 and PIN1 genes and diabetes. Logistic regression analysis was performed to calculate the odds ratio (ORs) (95% confidence interval (CI)) for the association between the four SNPs.ResultsAdjusted for age, weight, waist circumference, drinking, smoking, hypertension, and diabetes, high pulse pressure risk was significantly higher for carriers with the rs4808278-TT genotype in BRD4 than those with wild genotypes (OR: 0.400, 95% CI: 0.217–0.737, P* < 0.05). However, we did not find any significant association of rs2233678, rs2287838, and rs2233682 in PIN1 with high pulse pressure susceptibility after covariate adjustment. GMDR analysis indicated a significant three-locus model (P = 0.0107) involving rs4808278, rs2233678, and diabetes, the cross-validation consistency of the three-locus models was 9/10, and the testing accuracy was 57.47%.ConclusionsGenetic mutations within BRD4 (rs4808278) could affect the susceptibility to high pulse pressure in a southeastern Chinese population.

The Association Analysis of GPNMB rs156429 With Clinical Manifestations in Chinese Population With Parkinson's Disease.

Background: The mechanisms of Parkinson's disease (PD) include complicated genetic factors. The roles of newly found risk genes need to be further verified among different ethnicities. In a two-stage meta-analysis, single nucleotide polymorphism (SNP) of rs156429 in glycoprotein non-metastatic melanoma protein B (GPNMB) was reported to be associated with PD. So far clinical studies have focused on association between rs156429 and PD onset, however there is little evidence linking rs156429 with PD symptoms.Objective: This study aimed to investigate the possible association of GPNMB rs156429 with PD manifestations among southeastern Chinese people.Methods: Demographic variables, disease-related factors, and motor and non-motor assessments of 511 PD patients were collected. Polymerase chain reaction (PCR) and SNaPshot technique were used to detect GPNMB rs156429. The associations of rs156429 with PD rating scales and clinical manifestations were analyzed by Kruskal-Wallis test and logistic regression model separately.Results: Kruskal-Wallis test and logistic regression model failed to reveal an association between GPNMB rs156429 and scores from Montreal Cognitive Assessment (MoCA) (p = 0.037; p = 1.000 after correction), and pain symptoms of 511 PD patients (p = 0.008, OR = 0.59, 95% CI = 0.40–0.87, overdominant model after adjustment; p = 0.168 after correction, overdominant model after adjustment). However, further analysis based on genders showed that GPNMB rs156429 might have a trend for being associated with cognitive dysfunction (Mini-Mental State Examination (MMSE), p = 0.064 after correction; MoCA, p = 0.064 after correction) and pain symptoms (p = 0.063 after correction, overdominant model after adjustment) in female PD patients but not male patients.Conclusions: This study revealed that GPNMB rs156429 might have a trend for being associated with cognitive dysfunction and pain symptoms of female PD patients in the southeastern Chinese population. Further studies from a larger sample size are needed to confirm these findings.

Chromosome 10q25 polymorphism is associated with susceptibility to large artery atherosclerotic stroke

Background and aimsA recent genome-wide association study (GWAS) reported an association between a single nucleotide polymorphism (SNP) rs11196288 and risk of early-onset large artery atherosclerotic (LAA) stroke in European population. The interaction between genetic and environmental factors such as age has also received increasing attention. We performed this study to investigate the association between the rs11196288A > G polymorphism and LAA stroke risk in the Chinese Han population and test whether age interacts rs11196288 to influence LAA stroke risk. MethodsGenotyping of rs11196288 was performed in 1066 LAA stroke patients and 1167 healthy controls. Multivariate logistic regression analyses were applied to assess the effect of the rs11196288A > G polymorphism on susceptibility and short-term outcome of LAA stroke. Nomograms were performed to estimate probability of risk for an individual patient. ResultsA significant decrement of LAA stroke risk was found in co-dominant (AG vs. AA, OR = 0.76, 95% CI = 0.64–0.91, P = 0.003; GG vs. AA, OR = 0.65, 95% CI = 0.50–0.85, P = 0.002), dominant (AG/GG vs. AA, OR = 0.74, 95% CI = 0.62–0.87, P < 0.001) and recessive models (GG vs. AA/AG, OR = 0.76, 95% CI = 0.59–0.97, P = 0.028) of rs11196288. However, the interaction between age and genotypes of rs11196288 was not statistically significant, and no significant association was observed between the rs11196288A > G polymorphism and short-term outcome of LAA stroke (P > 0.05). ConclusionsIn the southeastern Chinese population, the rs11196288A > G polymorphism is associated with decreased risk of LAA stroke.

Gender-specific association between Apelin/APJ gene polymorphisms and hypertension risk in Southeast China

To explore the role of genetic factors in the pathogenesis of hypertension, our study investigated the gender-specific association between four polymorphisms in the Apelin/APJ gene and hypertension risk in southeastern Chinese population. All participants including 645 hypertensive patients and 362 normotensive controls were genotyped for 4 gene polymorphisms associated with hypertension susceptibility including Apelin (rs909656, rs5975126) and APJ (rs10501367, rs11544374). According to genotype analysis, for male subjects, the frequencies of genotypes (P = 0.046 and 0.046, respectively) of rs10501367 and rs11544374 revealed significant differences between the hypertension and control groups. Moreover, for female subjects, there was significant difference on the genotype distribution of rs11544374 between two groups (P = 0.046). The association of rs10501367 with hypertension was significant for males under additive models and recessive models, even after adjusting for age, BMI, fasting glucose and waistline. Besides, significant association was observed for rs11544374 in females under additive models. As for haplotype analysis, haplotype T-A (in order of rs10501367 and rs11544374) in APJ gene was marginally overrepresented in controls (17.9%) compared to patients with hypertension (11.6%) in males (P = 0.003). The mutation of polymorphism rs10501367 in APJ gene decreased risk of hypertension in Chinese males.

Morphologic features of the distal femur and tibia plateau in Southeastern Chinese population: A cross-sectional study.

Morphologic measurements of the femoral and tibial features of western population have been done in several studies, which provides the fundamental data for the design of total knee arthroplasty prosthesis used globally, including China. However, researches on anatomic and morphologic features of the knee in Chinese populations of both sexes have never been conducted. Our study was aimed at investigating the anatomic and morphologic features of the knees of the Southeastern Chinese population by magnetic resonance imaging (MRI) scans, so as to provide parameters for sex- and ethnic-specific implant designs in the future.A total of 245 knees from 244 Chinese adults (130 females and 114 males, aging from 18 to 89 years) who received knee MRI scan from November 2014 to October 2015 were recruited and analyzed. A set of linear and angular parameters, and 6 normalized ratios were measured and calculated on the distal femur and proximal tibia.The knee size was significantly different between sexes. Compared with women, men have larger (P < .01) medial-lateral (ML) and anterior-posterior (AP) dimensions in both distal femur and proximal tibia. Differences in femoral shape, represented by the femur surface ratio, between both sexes were also identified (1.23 ± 0.07 vs 1.27 ± 0.07, P < .01), whereas the ML/AP ratios of the tibia are similar between both sexes (1.44 ± 0.07 vs 1.44 ± 0.09, P = .97). We also found substantial difference in the morphology of femur and tibia plateau in Southeastern Chinese population compared with data obtained from western populations.Our study measured the anatomic and morphologic features of the knees in Southeastern Chinese population, and identified knee morphologic differences between both sexes, as well as western and Chinese population. Further clinical studies are needed to determine other essential parameters for the design of prosthesis to the Chinese populations.

Association of interleukin-6 gene polymorphisms and circulating levels with keloid scars in a Chinese Han population.

The aim of the present study is to explore the effect of IL-6 gene polymorphisms on the development of keloid scar (KS) in the Chinese Han population. Genotyping of IL-6 was performed by the polymerase chain reaction (PCR), followed by restriction fragment length polymorphism assays (PCR-RFLP). Serum level of IL-6 was measured using enzyme-linked immunosorbent assay (ELISA). Results indicated that when the IL-6 -572 CC homozygote genotype was used as the reference group, the GG genotype was found to be associated with a significantly increased risk of KS (GG vs CC: OR = 2.097, 95%CI = 1.100-3.995, P = 0.025). When the IL-6 -572 C allele was used as the reference group, the G allele was found to be associated with significantly increased risk of KS (G vs C: OR = 1.317, 95%CI = 1.002-1.730, P = 0.048). Furthermore, we observed a marked increase in serum IL-6 levels in KS patients with GG genotypes when compared to KS patients harboring the CC genotype. In conclusion, our results suggest that IL-6 gene polymorphism was associated with keloid scars in the southeastern Chinese Han population.

Risk factors for intestinal metaplasia in a southeastern Chinese population: an analysis of 28,745 cases.

To identify risk factors for intestinal metaplasia in a southeastern Chinese population. Subjects who underwent upper GI endoscopy and endoscopic biopsy in the First Affiliated Hospital of Nanjing Medical University from 2008 to 2013 were included into this study. Various demographic, geographic, clinical and pathological data were analyzed separately to identify risk factors for intestinal metaplasia. The incidence of intestinal metaplasia differed significantly in 17 municipal areas ranging from 16.79 to 38.56% and was positively correlated with the age range of 40-70years, male gender, gastric ulcer, bile reflux, Helicobacter pylori infection, atrophic gastritis, dysplasia, gastric cancer, degree of chronic and acute inflammation, and gross domestic product per capita (P<0.01). Multivariate linear regression analysis indicated that only gross domestic product per capita revealed a significant difference in the incidence of intestinal metaplasia among all factors mentioned. This study confirms age, male gender, gastric ulcer, bile reflux, H. pylori infection, severe degree of chronic and acute inflammation to be the risk factors for intestinal metaplasia. We speculate that the gross domestic product per capita of different areas may be a potential independent risk factor impacting the incidence of intestinal metaplasia.

MICA Gene Deletion in 3411 DNA Samples from Five Distinct Populations in Mainland China and Lack of Association with Nasopharyngeal Carcinoma (NPC) in a Southern Chinese Han population.

Deletion of major histocompatibility complex class I chain-related genes A (MICA*Del) was investigated in 3,411 DNA samples from two southern Chinese Han populations (Hunan Han, HNH; Guangdong Han, GDH), two northern Chinese populations (Inner Mongolia Han, IMH; Inner Mongolia Mongol, IMM) and one southeastern Chinese Han population (Fujian Han, FJH) using an in-house polymerase chain reaction-sequence specific priming (PCR-SSP) assay, which enables direct discrimination between heterozygote and homozygote for MICA*Del. MICA*Del showed a frequency ranging from 0.8% in FJH to 5.7% in IMM (Pcorrected < 0.05), indicating northward increase in frequency of MICA*Del in Chinese populations. In contrast to the association reported recently in a Taiwan Chinese population and aMalaysian Chinese cohort, MICA*Del distribution did not differ between 1,120 patients with nasopharyngeal carcinoma (NPC) and 1,483 normal controls in the HNH population (1.03% in NPC cases vs 1.18% in the controls, OR (95% CI) = 0.87 (0.51-1.47), p = 0.69). Further gender-stratified analysis also failed to disclose any male-specific association reported in a Taiwan Chinese population. Multi-locus typing of the 94 samples carrying MICA*Del revealed two new haplotypes, HLA-A*11:01-B*13:01-MICA*Del-MICB*009N-DRB1*04:06 and HLA-B*35:01-MICA*Del-MICB*009N-DRB1*15:01, in addition to HLA-B*48-MICA*Del. Unexpectedly, two samples with MICA*Del in the HNH population were each consistently found to have two distinct MICA alleles, indicating the existence of two MICA gene copies on certain HLA haplotypes. Based on the results from a sizeable case-control study, our data suggest that there is no association between MICA*Del and NPC in the southern Chinese Han population.

NKG2C copy number variations in five distinct populations in mainland China and susceptibility to nasopharyngeal carcinoma (NPC)

In this study, copy number variation (CNV) of NKG2C gene was investigated in 1129 normal, unrelated individuals representing two southern Chinese Han populations (Hunan Han and Guangdong Han), two northern Chinese populations (Inner Mongolia Han and Inner Mongolia Mongol) and one southeastern Chinese Han population (Fujian Han) using polymerase chain reaction-sequence-specific priming (PCR-SSP) method. CNV of NKG2C gene did not vary significantly among the five Chinese populations, with NKG2C gene deletion showing a frequency ranging from 0.2031 to 0.2688. Compared with worldwide ethnic groups, very significant difference was observed between the five Chinese populations and the Mexican mestizos (all Pcorrected=0.0025), and between the Fujian Han population and the German population (Pcorrected=0.005). We further examined CNV of NKG2C and HLA-E allelic distribution in 653 patients afflicted with nasopharyngeal carcinoma (NPC) in Hunan province. Neither CNV of NKG2C nor HLA-E was associated with NPC. There was a trend of reduced NPC risk in individuals who were homozygous for both HLA-E∗01:03 and NKG2C deletion (0.46% vs. 2.51%, P=0.0076, Pcorrected=0.0684, OR (95% CI)=0.1794 (0.0473–0.6809)). Taken together, our results suggest that NKG2C deletion and HLA-E signalling pathway does not play a major role in determining genetic susceptibility to NPC.

Ischemic stroke risk in a southeastern Chinese population: Insights from 5-lipoxygenase activating protein and phosphodiesterase 4D single-nucleotide polymorphisms

Through a genome-wide linkage scan, an Icelandic genetic research group identified two new genes associated with ischemic stroke: the 5-lipoxygenase activating protein (ALOX5AP) gene and the phosphodiesterase 4D (PDE4D) gene. Because they regulate arterial inflammation and are closely related to atherosclerosis and plaque instability, these two mutated genes have become a research hotspot. The purpose of this study was to investigate the association between the risk of ischemic stroke and single-nucleotide polymorphisms (SNPs) in the ALOX5AP and PDE4D genes in a southeastern Chinese population. A total of 459 patients with stroke and 462 control individuals were recruited in the study. Four ALOX5AP SNPs (SG13S32, SG13S42, SG13S89, and SG13S114), and three PDE4D SNPs (SNP83, SNP87, and SNP45) were studied. SNP genotypes were determined by polymerase chain reaction amplification followed by allele-specific primer extension, with detection by matrix-assisted laser desorption/ionization time-of-flight. Data were coded and entered in SPSS Windows (version 16.0). Odds ratios and 95% confidence intervals were calculated using multivariate logistic regression analysis. Generalized multifactor dimensionality reduction (GMDR) analysis was applied to detect gene-gene interactions. No statistically significant differences were found in the SNP genotype frequencies between cases and controls for the seven SNPs studied. GMDR analysis revealed no evidence of interactions between these seven polymorphic sites and an increased stroke risk. In addition, no association between different stroke types and the control group was detected. Results showed that only the ALOX5AP gene, and specifically the rs9551963 and rs4769060 genotypes, exhibited significantly different distributions between the stroke and control groups in female participants. No association was found between SNPs of ALOX5AP or PDE4D and the risk of overall ischemic stroke in a southeastern Chinese population. Interactions between these two genes were not risk factors for cerebral infarction. In atherothrombotic and small-artery disease subtypes, none of the seven SNPs was associated with any stroke risk; however, the ALOX5AP gene might be related to ischemic stroke incidence in females.

High frequency of Machado-Joseph disease identified in Southeastern Chinese kindreds with spinocerebellar ataxia

BackgroundMachado-Joseph disease (MJD), caused by a CAG repeat expansion located in exon10 of the ATXN3 gene, is now regarded as one of the most common spinocerebellar ataxia (SCA) in the world. The relative frequency of MJD among SCA has previously been estimated at about 50% in the Chinese population and has been reported to be related to the frequency of large normal alleles in some populations. Taq polymerase has been used for PCR in nearly all studies reported previously.MethodsNormal and expanded alleles of ATXN3 were detected via PCR using LA Taq DNA polymerase (better for GC-rich sequences) and denaturing polyacrylamide gel electrophoresis in 150 normal individuals and 138 unrelated probands from autosomal dominant SCA families. To compare reaction efficiency, 12 MJD patients' expanded alleles were amplified with La Taq and Taq polymerase respectively in the same amplifying systems and reaction conditions.ResultsNormal alleles ranged from 12 to 42 CAG repeats. The most common allele contained 14 repeats with a frequency of 23.3%, which corroborates previous reports. The frequency of large normal alleles (>27 repeats) was 0.28, which was very high relative to previous reports. The frequency of MJD in SCA patients was 72.5%, which was significantly higher than those in previous reports about the Chinese and other Asian populations. This frequency was one of the highest reported worldwide, with only Portuguese and Brazilian populations exhibiting higher proportions. All 12 expanded alleles were amplified in PCR with La Taq polymerase, whereas only 2 expanded alleles were amplified with Taq polymerase.ConclusionWe have first reported the highest relative frequency of MJD in Asia, and we attribute this high frequency to a more efficient PCR using LA Taq polymerase and hypothesized that large ANs may act as a reservoir for expanded alleles in the Southeastern Chinese population.

Toll‐like receptors 2 and 4 gene polymorphisms in a southeastern Chinese population with tuberculosis

Polymorphisms of the toll-like receptor 2 (TLR2) gene (Arg677Trp, Arg753Gln) and the TLR4 gene (Asp299Gly, Thr399Ile) were investigated in 205 tuberculosis (TB) patients and 203 controls. Genetic variations were analysed by DNA sequencing. We revealed that these polymorphisms were rare in the southeastern Chinese population and were not associated with susceptibility to TB.

Polymorphisms of TLR7 and TLR8 associated with risk of asthma and asthma-related phenotypes in a southeastern Chinese Han population

Objective To evaluate the effects of polymorphisms in TLR7 and TLR8(as potential candidate genes) on asthma risk and asthma-related phenotypes. Methods We consecutively recruited 318 unrelated adult asthmatic patients and 352 healthy volunteers from the same area of southeast China. Genotyping of each selected SNP was performed using multiplex PCR in conjunction with tagged array single base extension technology. We conducted case-control and case-only association studies between the selected SNPs in TLR7 and TLR8 and asthma or asthma-related phenotypes. Results The T allele of rs5935436 SNP in TLR7 was protective from developing asthma in males (adjusted ORs = 0.126, 95% CIs = 0.016-0.995). The CT/TT genotype of rs5935436 was less frequent in female asthmatics with allergic rhinitis (adjusted ORs = 0.18, 95% CIs = 0.04-0.90). The homozygote AA of rs3761623 and GG of rs3764880 were positively associated with lower FEV 1% and asthma severity in female asthmatics. These results were confirmed by haplotype analysis. Conclusion TLR7 and TLR8 polymorphisms may play an important role in the pathogenesis of asthma that is gender-dependent. This could be clinically useful, both for identifying patients at risk of asthma and for preventing its occurrence.

Association between polymorphisms in the GSTA4 gene and risk of lung cancer: A case–control study in a Southeastern Chinese population

GST Alpha 4 (GSTA4) has an important role in the protection against oxidative stress induced by carcinogens such as tobacco smoke. However, few studies investigated the association between GSTA4 polymorphisms and lung cancer risk. We genotyped three selected GSTA4 SNPs (rs182623 - 1718:T > A, rs3798804 + 5034:G > A and rs316141 + 13984:C > T) in a case-control study of 500 lung cancer patients and 517 cancer-free controls and evaluated the association between these SNPs and risk of lung cancer in this Han Chinese population. We found that there was a significant difference in genotype and allele frequency distributions of GSTA4 -1718 between the cases and the controls (P = 0.006 and P = 0.003, respectively). Compared with the GSTA4 -1718TT genotype, individuals with the TA + AA genotypes had a significantly decreased risk of lung cancer (adjusted OR, 0.63; 95% CI, 0.47-0.84; P = 0.006). Although there were no such statistical differences between the cases and controls at the loci +5034 and +13984, nor for histological types, individuals carrying the genotypes of -1718TA, +5034GG and +13984CT had a significantly decreased lung cancer risk (OR, 0.37; 95% CI, 0.23-0.61; P < 0.0001), especially for those smokers who smoked </=25 pack-years (P < 0.000001). These results need to be confirmed in larger studies with different ethnic groups.

Interferon Gamma Receptor 1 Gene Polymorphism in Patients with Tuberculosis in China

The aim of the study was to examine the influence of the CA microsatellite polymorphisms of interferon gamma receptor 1 on patients with tuberculosis (TB) in the south-eastern Chinese population. Genomic DNA from patients with TB (n = 155) and ethnically matched controls (n = 89) were genotyped by short tandem repeat-PCR method. The allele frequency of (CA)(25) was 1.70-fold higher among patients than that among controls (95% CI 1.07-2.70) (P = 0.025). Compared with the non-(CA)(25)/non-(CA)(25) reference group, the risk to TB of the carriers of (CA)(25)/(CA)(25) genotypes were 6.46-fold (95% CI 1.40-29.74) (P = 0.0017) higher. On the contrary, the allele frequency of (CA)(26) was 0.29-fold lower in patients than that in controls (95% CI 0.11-0.76) (P = 0.012). Genotypes with (CA)(26) allele were at 0.35-fold (95% CI 0.13-0.98) (P = 0.045) lower to the risk of TB, compared with that of the non-(CA)(26)/non-(CA)(26) in the reference group. The above results indicated that the allele (CA)(25) appeared to be susceptible to TB, while the allele (CA)(26) to be protective towards TB. Our data also suggest that the CA repeat was a highly polymorphic marker and could be used for linkage and association analysis.

Genetic variants of the cytochrome P450 and glutathione S‐transferase associated with risk of bladder cancer in a south‐eastern Chinese population

To evaluate the association between genetic polymorphisms of CYP2E1 RsaI and GSTM1 and development of bladder cancer in a south-eastern Han Chinese population. We hypothesized that the CYP2E1-1019T>A and GSTM1 polymorphisms were associated with risk of bladder cancer. In a hospital-based case-control study of 202 case patients with newly diagnosed bladder transitional cell carcinoma and 272 cancer-free controls frequency-matched by the age and sex, we genotyped these two polymorphisms using a polymerase chain reaction-restriction fragment length polymorphism method. We found that the GSTM1 null genotype was associated with an increased risk of bladder cancer (adjusted odds ratio [OR] = 1.73, 95% confidence interval [CI] = 1.17-2.56) compared with those with the non-null genotype, but the CYP2E1-1019T>A polymorphisms did not show any association. In the stratification analysis of the GSTM1 polymorphism, we found that the increased risk was more pronounced among subgroups aged < or =60 years (OR = 2.02, 95% CI = 1.08-3.77), smokers (OR = 1.94, 95% CI = 1.11-3.38) and non-drinkers (OR = 3.86, 95% CI = 1.28-11.60). GSTM1 polymorphism (but not CYP2E1 RsaI polymorphism) appears to contribute to the etiology of bladder cancer in a south-eastern Chinese population.

Polymorphism of the interferon-γ gene and risk of tuberculosis in a southeastern Chinese population

The aim of this study is to examine the influence of the +874 A/T and +875 CA microsatellite single nucleotide polymorphisms (SNPs) of the interferon-gamma gene (IFNG) on patients with tuberculosis (TB) in the southeastern Chinese population. Genomic DNA from patients with TB (n = 301) and ethnically matched controls (n = 310) was genotyped for the two SNPs by DNA sequencing and short tandem repeat-polymerase chain reaction (PCR) method. Our results demonstrated the AA genotype of +874 A/T IFNG was associated with TB (odds ratio, 1.98; 95% confidence interval = 1.08-3.63; p = 0.035). By grouping alleles into 12 and non-12 CA repeats at the +875 CA microsatellite, the homozygous non-12/non-12 CA repeats genotype yielded the same significant trend as that observed in the +874 AA genotype. The results indicate a positive association of IFNG polymorphism with TB. Data also provide genetic evidence supporting the multiple disease hypothesis, which emphasizes that many disease genes have been involved.

Polymorphisms of the DNA gene XPD and risk of bladder cancer in a Southeastern Chinese population

The incidence rate for bladder cancer has been increasing in many countries, and bladder cancer is the most common urinary cancer in China. We explored the association of single-nucleotide polymorphisms in DNA repair genes with bladder cancer. The hypothesis is that the xeroderma pigmentosum complementary group D ( XPD) 156-22541C→A and 751-35931A→C polymorphisms are associated with the risk of bladder cancer. In a population-based case-control study, 215 patients with newly diagnosed bladder transitional cell carcinoma and 245 cancer-free controls/healthy subjects (frequency-matched by the age and sex) were genotyped. These two polymorphisms were studied using the polymerase chain reaction restriction fragment length polymorphism method. We found that the A allele of XPD Arg156Arg (C22541A) and the C allele of XPD Lys751Gln (A35931C) is associated with increased risk of bladder cancer (adjusted odds ratio = 1.54 and 95% confidence interval = 1.19–2.01, 1.65, and 1.12–2.73, respectively). Smoking is also a risk factor in the etiology of bladder cancer, but alcohol intake is a protective factor during the development of bladder cancer. These two XPD polymorphisms may play an important role in the etiology of bladder cancer in the southeastern Chinese population.