CYP2C19 Polymorphism and Clinical Outcomes among Patients of Different Races Treated with Clopidogrel:A Systematic Review and Meta-Analysis

Several studies have investigated the association between CYP2C19 polymorphism and clinical outcomes of patients treated with clopidogrel, but few have noticed the difference in association between Westerners and Asians. We searched MEDLINE, EMBASE and Cochrane Library database and conducted a systematic review and meta-analysis. Thirty-six studies involving 44 655 patients with coronary artery disease（CAD） treated with clopidogrel were included, of which more than 68% had undergone percutaneous coronary intervention（PCI）. The primary outcome of our interest was the recurrence of major adverse cardiovascular events（MACE） in those CAD patients. Firstly, we found that the distribution of reduced-function CYP2C19 allele varied between Westerners and Asians. Among Asians, 1 and 2 reduced-function CYP2C19 mutant allele carriers accounted for 42.5% and 10%, respectively. While among Westerners, 1 and 2 reduced-function CYP2C19 mutant allele carriers accounted for 25.5% and 2.4%, respectively. Secondly, the impact of CYP2C19 polymorphism on clinical outcomes of patients treated with clopidogrel varied with races. Among Asians, only 2 reduced-function CYP2C19 mutant allele carriers had the reduced effect of clopidogrel. And the reduced effect was significant only after the 30 th day of treatment. While among Westerners, both 1 and 2 reduced-function CYP2C19 allele carriers had the reduced effect, and it mainly occurred within the first 30 days. Thirdly, the safety of clopidogrel was almost the same among races. Reduced-function allele non-carriers had higher risk for total bleeding but did not have higher risk for major bleeding. It is suggested that CYP2C19 polymorphism affects the efficacy of clopidogrel differently among Westerners and Asians.

Association of Single Nucleotide Polymorphisms of ABCB1,OPRM1 and COMT with Pain Perception in Cancer Patients

Pain perception is influenced by multiple factors. The single nucleotide polymorphisms（SNPs） of some genes were found associated with pain perception. This study aimed to examine the association of the genotypes of ABCB1 C3435 T,OPRM1 A118 G and COMT V108/158M（valine 108/158 methionine） with pain perception in cancer patients. We genotyped 146 cancer pain patients and 139 cancer patients without pain for ABCB1 C3435T（rs1045642）,OPRM1 A118G（rs1799971） and COMT V108/158M（rs4680） by the fluorescent dye-terminator cycle sequencing method,and compared the genotype distribution between groups with different pain intensities by chi-square test and pain scores between groups with different genotypes by non-parametric test. The results showed that in these cancer patients,the frequency of variant T allele of ABCB1 C3435 T was 40.5%; that of G allele of OPRM1 A118 G was 38.5% and that of A allele of COMT V108/158 M was 23.3%. No significant difference in the genotype distribution of ABCB1 C3435T（rs1045642） and OPRM1 A118G（rs1799971） was observed between cancer pain group and control group（P=0.364 and 0.578）; however,significant difference occurred in the genotype distribution of COMT V108/158M（rs4680） between the two groups（P=0.001）. And the difference could not be explained by any other confounding factors. Moreover,we found that the genotypes of COMT V108/158 M and ABCB1 C3435 T were associated with the intensities of pain in cancer patients. In conclusion,our results indicate that the SNPs of COMT V108/158 M and ABCB1 C3435 T significantly influence the pain perception in Chinese cancer patients.

Toll-like Receptor Polymorphisms and Tuberculosis Susceptibility:A Comprehensive Meta-analysis

The polymorphisms of toll-like receptor（TLR） have been hypothesized to affect the tuberculosis susceptibility. However, the direct evidence remains controversial. Here we performed a comprehensive meta-analysis to summarize the associations between TLR polymorphisms and tuberculosis susceptibility. We systematically searched the Pub Med, Embase, Cochrane library, and Chinese National Knowledge Infrastructure up to April 25, 2014. Case-control studies investigating TLR polymorphisms and tuberculosis susceptibility were included in the meta-analysis. Pooled odds ratios and corresponding 95% confidence intervals were calculated for cases and controls. Stata 11.0 and Review Manager 5.1 were adopted to conduct statistical analysis. We included 29 studies, involving 17 804 individuals. The results revealed an obvious increase of tuberculosis risk in TLR2 2258 AA, and decreased risk in TLR6 745 TT and TLR8 rs3761624 GA genotypes. Meanwhile, different genetic models were performed. TLR8 rs3764879 C, TLR8 rs3761624 A and TLR8 rs3764880 A alleles were associated with high susceptibility, while TLR6 745 T and TLR8 rs3788935 C alleles were protective. Other polymorphisms, including TLR9 1486C/T, did not show significant associations with tuberculosis infection. Finally, subgroup analysis in TLR8 rs3764880 according to gender found a slight elevated effect of A allele in males. The meta-analysis suggests significant associations between several TLR polymorphisms and tuberculosis, including TLR2 2258G/A, TLR6 745C/T, TLR8 rs3761624, TLR8 rs3764879, TLR8 rs3761624 and TLR8 rs3764880. This study serves as the framework for additional studies to determine further the role of TLRs in tuberculosis infection.