Haplotype analysis of the CYP2J2 gene associated with myocardial infarction in a Chinese Han population

The cytochromes P450 epoxygenases CYP2J2 synthesize epoxyeicosatrienoic, which regulate endothelial function. The aim of this study was to assess the association between the human CY2J2 gene and myocardial infarction (MI) in a Chinese population using a haplotype‐based case–control study. There were 440 Chinese Han MI patients and 440 age‐matched control subjects genotyped for three SNPs (rs2271800, rs11572223, and rs14493270) of the human CYP2J2 gene. Haplotypes were constructed and their frequencies compared between the MI patients and the controls. The CC genotype of rs2271800 was found more frequently in the MI group than in the control group (p = 0.004). The frequency of the C–C–G haplotype was significantly higher in MI patients than in control subjects (p < 0.001). The present results indicate that MI is associated with the CC genotype of rs2271800 in the human CYP2J2 gene. The C–C–G haplotype appears to be a useful genetic marker of MI in Chinese Han people. Copyright © 2010 John Wiley & Sons, Ltd.     

Association between polymorphism of the cyclin E1 gene and susceptibility to hepatocellular carcinoma in Chinese Han population of Hubei

This study aimed to explore the relationship between CCNE1 gene single nucleotide polymorphisms (SNP rs1406 and rs3218038) and the incidence of hepatitis B virus-related hepatocellular carcinoma (HCC) in the Chinese Han population in Hubei. A total of 663 subjects, including 173 HCC patients, 172 HBV-related liver cirrhosis (LC) patients, 162 asymptomatic HBV carriers (AsC), and 156 healthy controls, participated in the study. Genotyping of CCNE1 rs1406 and rs3218038 polymorphisms was done by illumina second generation sequence method.Our findings showed that rs1406 G>T variant decreased the risk of HCC (OR 0.710, P=0.035 G vs T), and no significant differences were found between rs3218038 SNP and HCC risk using the χ² test. Furthermore, stratified analysis revealed that differences in genotype frequencies were related to gender. Women who carried the CCNE1 GT genotype were significantly associated with a decreased risk of HCC, compared with healthy controls carrying the GG genotype (additive model, OR 0.378,P=0.030).The results suggest that the rs1406 G allele and CCNE1 rs1406 polymorphism produce an increased the risk of HCC in comparison with the T allele. Whereas, the GT genotype is a protective factor in the development of HCC in female patients.     

The Per2 polymorphism rs10462023 is associated with the risk of stroke in a Chinese population

The key clock protein Period2 (Per2) has been suggested to play an essential role in regulating endothelial function. It also regulates the expression of plasminogen activator inhibitor-1, but its role in stroke development has not been studied. To explore the possible association between Per2 and ischemic stroke (IS), 479 Chinese IS patients and 306 healthy controls were recruited, and five tag single nucleotide polymorphisms representing the Per2 locus were genotyped using the Sequenom MassARRAY system. A significant difference was observed in the genotypic distribution (p = 0.014) and allele frequency (p = 0.005) of rs10462023, with carriers of the G allele being more prone to developing IS. After adjusting for possible risk factors including smoking, alcohol use, and history of hypertension and diabetes, a significant association was still apparent. Haplotype analysis also supported the association between Per2 and IS. This study suggests that Per2 variations are associated with IS and may represent genetic risk factors for IS in a Chinese population.     

A lack of association between adiponectin polymorphisms and coronary artery disease in a Chinese population

We investigated the association between two single nucleotide polymorphisms (SNPs) in the adiponectin gene (rs822395 and rs266729) and coronary artery disease (CAD) in a case-control study of 198 unrelated Chinese CAD patients (with ≥ 70% coronary stenosis or previous myocardial infarction) and 237 non-CAD controls. The ligase reaction was used to detect SNPs rs822395 and rs266729, and the allelic association of these SNPs with the occurrence and severity of CAD was assessed. There were no significant differences in the genotypic or allelic frequencies of the two SNPs between control and CAD individuals. In addition, there was no association between the two SNPs and the severity of CAD based on the number of diseased vessels. The frequencies of alleles C and G at rs266729 differed significantly between females in the CAD and control groups, but not between males. Female carriers of allele G at rs266729 had a higher risk of CAD compared with allele C carriers (OR = 1.30, 95% CI: 1.09-2.64, p = 0.02). These results indicate a gender-specific effect of the adiponectin gene rs266729 variant in modulating the risk of CAD in women.     

Design and Analysis of Multiple Events Case–Control Studies

Summary In case–control research where there are multiple case groups, standard analyses fail to make use of all available information. Multiple events case–control (MECC) studies provide a new approach to sampling from a cohort and are useful when it is desired to study multiple types of events in the cohort. In this design, subjects in the cohort who develop any event of interest are sampled, as well as a fraction of the remaining subjects. We show that a simple case–control analysis of data arising from MECC studies is biased and develop three general estimating‐equation‐based approaches to analyzing data from these studies. We conduct simulation studies to compare the efficiency of the various MECC analyses with each other and with the corresponding conventional analyses. It is shown that the gain in efficiency by using the new design is substantial in many situations. We demonstrate the application of our approach to a nested case–control study of the effect of oral sodium phosphate use on chronic kidney injury with multiple case definitions.     

Association analysis between MDR1 gene polymorphisms and risk of hepatocellular carcinoma in Chinese population

Objective: XRCC4 play a key role in nonhomologous end-joining repair pathway. Alterations in DNA repair gene have been shown to reduce DNA repair capacity thereby inflicting carcinogenesis.

Methods: In a hospital-based case-control study, 192 prostate cancer (PCa) and 224 healthy controls. They were genotyped for XRCC4 G-1394T (rs6869366), intron 3 (rs28360071) intron 7 (rs28360317) and intron 7 (rs1805377), polymorphisms using polymerase chain reaction–restriction fragment length polymorphism.

Result: Carriers of GG genotype of rs6869366 were at reduced risk. Del/Del of rs28360071 and 28360317 demonstrated increased risk. The haplotype analysis was observed to be associated with a significant increase in PCa risk. Combined genotype of rs6869366, rs28360071 and rs1805377 have shown significant risk with high Gleason grade.

Conclusion: Our results suggested that the variant genotype of XRCC4 rs28360071 and rs28360317 and haplotype analysis may be associated with PCa risk.     

Association between the PRNP 1368 polymorphism and the occurrence of sporadic Creutzfeldt-Jakob disease

Creutzfeldt-Jakob disease (CJD) is a rare transmissible neurodegenerative disorder. The etiology of sporadic form of CJD remains unsolved. In addition to the codon 129 polymorphism, polymorphisms in the non-coding region of PRNP are considered as important factors in sCJD development. To assess a possible association between PRNP 1368 SNP and sCJD, we compared the genotype, allele and haplotype frequencies of the 1368 SNP among 46 sCJD patients of Dutch origin with the respective frequencies in healthy controls. We detected a significant association between sCJD and 1368T/T genotype. A significant difference was also observed in 1368 alleles’ distribution. In the haplotype analysis, haplotype 1368C-129G was associated with decreased risk of sCJD in Dutch population. Our findings support the hypothesis that genetic variations in the regulatory region of the PRNP gene may influence the pathogenesis of sCJD.     

Association between the PRNP 1368 polymorphism and the occurrence of sporadic Creutzfeldt-Jakob disease

Creutzfeldt-Jakob disease (CJD) is a rare transmissible neurodegenerative disorder. The etiology of sporadic form of CJD remains unsolved. In addition to the codon 129 polymorphism, polymorphisms in the non-coding region of PRNP are considered as important factors in sCJD development. To assess a possible association between PRNP 1368 SNP and sCJD, we compared the genotype, allele and haplotype frequencies of the 1368 SNP among 46 sCJD patients of Dutch origin with the respective frequencies in healthy controls. We detected a significant association between sCJD and 1368T/T genotype. A significant difference was also observed in 1368 alleles’ distribution. In the haplotype analysis, haplotype 1368C-129G was associated with decreased risk of sCJD in Dutch population. Our findings support the hypothesis that genetic variations in the regulatory region of the PRNP gene may influence the pathogenesis of sCJD.     

Association between -251A>T polymorphism in the interleukin-8 gene and oral cancer risk: A meta-analysis

Background

Emerging evidence showed that the most common functional polymorphism (-251A>T, rs4073) in the promoter region of the interleukin-8 (IL-8) gene is involved in the regulation of the activities of interleukin-8, thus increasing an individual's susceptibility to oral cancer; but individually published results are inconclusive. The aim of this meta-analysis was to investigate the associations between IL-8 -251A>T polymorphism and oral cancer risk.

Methods

The PubMed, Embase, Web of Science and CBM databases were searched for all articles published up to October 1st, 2012 that addressed IL-8 -251A>T polymorphism and oral cancer risk. Statistical analyses were performed using STATA 12.0 software. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations.

Results

Six case–control studies were included with a total of 1324 oral cancer cases and 1879 healthy controls. When all available studies were pooled into the meta-analysis, the results showed that the AA and AT genotypes of IL-8 -251A>T polymorphism were associated with increased risk of oral cancer (OR = 1.23, 95% CI: 1.03–1.46, P = 0.025; OR = 1.25, 95% CI: 1.07–1.47, P = 0.006; respectively). In the subgroup analysis by ethnicity, significant associations were observed between the AA and AT genotypes of IL-8 -251A>T polymorphism and increased risk of oral cancer among Caucasian populations (OR = 1.40, 95% CI: 1.14–1.72, P = 0.001; OR = 1.29, 95% CI: 1.06–1.57, P = 0.011; respectively). However, no statistically significant associations were found between IL-8 -251A>T polymorphism and oral cancer risk among Asian populations.

Conclusions

Results from the current meta-analysis indicate that the AA and AT genotypes of IL-8 -251A>T polymorphism might increase the risk of oral cancer, especially among Caucasian populations.     

Lack of association between polymorphisms in the P2X7 gene and tuberculosis in a Chinese Han population

Several studies have suggested that genetic factors may affect the susceptibility of a population to tuberculosis, and it has been found that P2X7 is linked to an increased risk for tuberculosis in some West African, Southeast Asian, North American, and North European populations. To explore the potential role of P2X7 in the susceptibility to tuberculosis among members of the Chinese Han population, we evaluated the association of the 1513A→C and −762T→C polymorphisms in P2X7 with the risk for tuberculosis. PCR amplification of genomic DNA was followed by restriction fragment length polymorphism analysis, and allele-specific PCR was used. We found no significant differences in the genotypic and allelic frequencies of 1513A→C polymorphisms in 96 patients with tuberculosis compared with 384 control subjects [ P =0.856 and 0.316, respectively; odds ratio (OR) for the C allele=0.976; 95% confidence interval (CI)=0.755–1.262]. Similarly, no significant association was found between the −762T→C polymorphism and tuberculosis ( P =0.102 and 0.095 for the patients and controls, respectively; OR for the C allele=0.924; 95% CI=0.847–1.010). Thus, our analysis of P2X7 showed that the 1513A→C and −762T→C polymorphisms did not appear to be associated with the susceptibility of the Chinese Han population to tuberculosis.