ADH1B Arg47His Polymorphism Is Associated with Esophageal Cancer Risk in High-Incidence Asian Population: Evidence from a Meta-Analysis

with ESCC in Asian populations under a common ancestry scenario of the susceptibility loci, we combined all available studies into a meta-analysis.. Heterogeneity among studies and their publication bias were also tested. can bring more risk to ESCC (OR  = 13.46, 95% CI: 2.32–78.07). allele

Ethnic Related Selection for an ADH Class I Variant within East Asia

The alcohol dehydrogenases (ADH) are widely studied enzymes and the evolution of the mammalian gene cluster encoding these enzymes is also well studied. Previous studies have shown that the ADH1B*47His allele at one of the seven genes in humans is associated with a decrease in the risk of alcoholism and the core molecular region with this allele has been selected for in some East Asian populations. As the frequency of ADH1B*47His is highest in East Asia, and very low in most of the rest of the world, we have undertaken more detailed investigation in this geographic region.Here we report new data on 30 SNPs in the ADH7 and Class I ADH region in samples of 24 populations from China and Laos. These populations cover a wide geographic region and diverse ethnicities. Combined with our previously published East Asian data for these SNPs in 8 populations, we have typed populations from all of the 6 major linguistic phyla (Altaic including Korean-Japanese and inland Altaic, Sino-Tibetan, Hmong-Mien, Austro-Asiatic, Daic, and Austronesian). The ADH1B genotyping data are strongly related to ethnicity. Only some eastern ethnic phyla or subphyla (Korean-Japanese, Han Chinese, Hmong-Mien, Daic, and Austronesian) have a high frequency of ADH1B*47His. ADH1B haplotype data clustered the populations into linguistic subphyla, and divided the subphyla into eastern and western parts. In the Hmong-Mien and Altaic populations, the extended haplotype homozygosity (EHH) and relative EHH (REHH) tests for the ADH1B core were consistent with selection for the haplotype with derived SNP alleles. In the other ethnic phyla, the core showed only a weak signal of selection at best.The selection distribution is more significantly correlated with the frequency of the derived ADH1B regulatory region polymorphism than the derived amino-acid altering allele ADH1B*47His. Thus, the real focus of selection may be the regulatory region. The obvious ethnicity-related distributions of ADH1B diversities suggest the existence of some culture-related selective forces that have acted on the ADH1B region

Computing Power and Sample Size for Case-Control Association Studies with Copy Number Polymorphism: Application of Mixture-Based Likelihood Ratio Test

Recent studies suggest that copy number polymorphisms (CNPs) may play an important role in disease susceptibility and onset. Currently, the detection of CNPs mainly depends on microarray technology. For case-control studies, conventionally, subjects are assigned to a specific CNP category based on the continuous quantitative measure produced by microarray experiments, and cases and controls are then compared using a chi-square test of independence. The purpose of this work is to specify the likelihood ratio test statistic (LRTS) for case-control sampling design based on the underlying continuous quantitative measurement, and to assess its power and relative efficiency (as compared to the chi-square test of independence on CNP counts). The sample size and power formulas of both methods are given. For the latter, the CNPs are classified using the Bayesian classification rule. The LRTS is more powerful than this chi-square test for the alternatives considered, especially alternatives in which the at-risk CNP categories have low frequencies. An example of the application of the LRTS is given for a comparison of CNP distributions in individuals of Caucasian or Taiwanese ethnicity, where the LRTS appears to be more powerful than the chi-square test, possibly due to misclassification of the most common CNP category into a less common category

Why Functional Pre-Erythrocytic and Bloodstage Malaria Vaccines Fail: A Meta-Analysis of Fully Protective Immunizations and Novel Immunological Model

Background: Clinically protective malaria vaccines consistently fail to protect adults and children in endemic settings, and at best only partially protect infants. Methodology/Principal Findings: We identify and evaluate 1916 immunization studies between 1965-February 2010, and exclude partially or nonprotective results to find 177 completely protective immunization experiments. Detailed reexamination reveals an unexpectedly mundane basis for selective vaccine failure: live malaria parasites in the skin inhibit vaccine function. We next show published molecular and cellular data support a testable, novel model where parasite-host interactions in the skin induce malaria-specific regulatory T cells, and subvert early antigen-specific immunity to parasite-specific immunotolerance. This ensures infection and tolerance to reinfection. Exposure to Plasmodium-infected mosquito bites therefore systematically triggers immunosuppression of endemic vaccine-elicited responses. The extensive vaccine trial data solidly substantiate this model experimentally. Conclusions/Significance: We conclude skinstage-initiated immunosuppression, unassociated with bloodstage parasites, systematically blocks vaccine function in the field. Our model exposes novel molecular and procedural strategies to significantly and quickly increase protective efficacy in both pipeline and currently ineffective malaria vaccines, and forces fundamental reassessment of central precepts determining vaccine development. This has major implications fo

Understanding changing malaria transmission in a rural village, in coastal Tanzania, by assessment of IgG antibodies against Plasmodium falciparum and Anopheles gambiae antigens.

Background: The changing epidemiology of malaria in Sub-Saharan Africa over the last decade needs further understanding. A longitudinal project on the epidemiology of malaria was set up in the Nyamisati village, Rufiji District, Tanzania in 1985. Cross-sectional surveys have revealed a gradual decrease in parasite prevalence over the last 25 years, from >90% to 13% (by PCR), despite the absence of large scale control interventions. Although PCR improves the detection of low-level parasitemia, assessment of parasite prevalence alone may not fully reflect the level of exposure in a population. In order to further understand the long-term dynamics of malaria transmission in this setting, we combined an assessment of parasite prevalence with analyses of IgG antibodies against antigens of the P. falciparum parasite and a salivary antigen of the Anopheles vector. Methodology: The study included children 1-16 years old participating in cross-sectional surveys in Nyamisati village in 1995, 1999 and 2010. Parasite prevalence was established by microscopy and PCR. Detection and quantification of IgG antibodies against P. falciparum whole schizont extract (PfSE) and Anopheles gambiae salivary gland protein 6 (gSG6) were performed with enzyme-linked immunosorbent assay (ELISA). Levels of IgG antibodies against merozoite surface protein 1-19 (MSP-119) and merozoite surface protein 2 (MSP-2) were assessed using a multiplexed bead-based immunoassay. Results and conclusions: The prevalence of anti-PfSE IgG as well as the levels of IgG antibodies against MSP-119 and MSP-2 decreased between 1995 and 2010, with the most marked reduction among the youngest children (1-4 years of age). The levels of anti-gSG6-IgG were, however, relatively stable over time. These findings suggest a substantially decreased intensity of malaria transmission in the Nyamisati area over the past 15 years, without an equally evident decrease in the population level of exposure to the malaria vector

Association study of the Ile349val polymorphism of the gene ADH1C and alcohol dependence

OBJECTIVE: The aim of this study was to investigate the polymorphism Ile349Val of the enzyme alcohol dehydrogenase ADH1C gene among individuals with alcohol dependence syndrome (ADS) attending Alcoholics Anonymous (AA) meetings. METHODS: A total of 120 subjects residing in Rio de Janeiro city participated in this study. Subjects were divided into two groups: a group consisting of 54 individuals from the ADS group and 66 individuals that declared not having any alcohol dependence (control group). DNA was extracted from mouth epithelial cells by phenol-chloroform method and further submitted to amplification by polymerase chain reaction (PCR). RESULTS: Our results did not show differences between the genotypes of control individuals and ADS subjects. Nevertheless, we found increased rates of alcoholism in families of ADS subjects as compared to controls. CONCLUSIONS: Our results did not show any genotype difference on the ADH1C gene when control and AA genotypes are compared