Genetic Variant rs7758229 in 6q26–q27 Is Not Associated with Colorectal Cancer Risk in a Chinese Population

Background

A recent genome-wide association study has identified a new genetic variant rs7758229 in SLC22A3 for colorectal cancer susceptibility in a Japanese population, but it is unknown whether this newly identified variant is associated with colorectal cancer in other populations, including the Chinese population.

Methods

We examined the associations between rs7758229 and colorectal cancer risk among 1,147 cases and 1,203 controls matched by age and sex. Logistic regression model was used to assess the associations.

Results

No significant association was found between rs7758229 and colorectal cancer risk (OR = 0.95, 95%CI  = 0.84–1.09, P = 0.463). Similar results were observed in the stratification of tumor location (OR  = 0.94, 95%CI = 0.80–1.11, P = 0.481 for colon cancer, and OR  = 0.96, 95%CI  = 0.82–1.13, P = 0.621 for rectum cancer).

Conclusions

Our findings did not support an association between rs7758229 in 6q26-q27 and the risk of colorectal cancer in a Chinese population.     

Heterozygosity in an Isolated Population of a Large Mammal Founded by Four Individuals Is Predicted by an Individual-Based Genetic Model

Background

Within-population genetic diversity is expected to be dramatically reduced if a population is founded by a low number of individuals. Three females and one male white-tailed deer Odocoileus virginianus, a North American species, were successfully introduced in Finland in 1934 and the population has since been growing rapidly, but remained in complete isolation from other populations.

Methodology/Principal Findings

Based on 14 microsatellite loci, the expected heterozygosity H was 0.692 with a mean allelic richness (AR) of 5.36, which was significantly lower than what was found in Oklahoma, U.S.A. (H = 0.742; AR = 9.07), demonstrating that a bottleneck occurred. Observed H was in line with predictions from an individual-based model where the genealogy of the males and females in the population were tracked and the population''s demography was included.

Conclusion

Our findings provide a rare within-population empirical test of the founder effect and suggest that founding a population by a small number of individuals need not have a dramatic impact on heterozygosity in an iteroparous species.     

Filaggrin Gene Mutation c.3321delA Is Associated with Various Clinical Features of Atopic Dermatitis in the Chinese Han Population

Background

We confirmed that the filaggrin gene mutation c.3321delA is associated with atopic dermatitis in our previous genome wide association study of the Chinese Han population. c.3321delA is the most common filaggrin gene mutation in Chinese atopic dermatitis patients but is not present in European populations.

Objective

To investigate the genetic model for the c.3321delA mutation and to determine the correlation between c.3321delA and atopic dermatitis clinical phenotypes in the Chinese Han population.

Method

The filaggrin gene mutation c.3321delA was sequenced in 1,080 atopic dermatitis patients and 908 controls from the Chinese population. The χ² test, ANOVA,nonparametric tests and logistic regression were used to investigate the relationship between the c.3321delA genotype and atopic dermatitis clinical phenotypes in the Chinese Han population.

Results

Analyses of the genetic model revealed that the additive model best described the c.3321delA mutation (P = 3.09E-11, OR = 3.43, 95%CI = 2.38–4.96). Stratified analyses showed that the c.3321delA allele frequency distribution is significantly associated with concomitant skin xerosis (P = 1.68E-03, OR = 2.13,95%CI = 1.32–3.46), palmar hyperlinearity (P = 3.64E-17, OR = 4.0,95%CI = 2.86–5.70), white dermatographism (P = 4.25E-03, OR = 1.82,95%CI = 1.22–2.71), food intolerance (P = 1.51E-03, OR = 1.76,95%CI = 1.23–2.50) and disease severity ( P = 9.67E-05).

Conclusion

Our study indicates that the filaggrin gene mutation c.3321delA is associated with clinical phenotypes of atopic dermatitis in the Chinese Han population, which might help us gain a better understanding on the pathogenesis of atopic dermatitis.     

The Plasma B-Type Natriuretic Peptide Levels Are Low in Males with Stable Ischemic Heart Disease (IHD) Compared to Those Observed in Patients with Non-IHD: A Retrospective Study

Objective

Although the plasma B-type natriuretic peptide (BNP) level is a marker of heart failure, it is unclear whether BNP per se plays a pivotal role for pathogenic mechanisms underlying the development of ischemic heart disease (IHD). In this study, we retrospectively examined the plasma BNP levels in stable patients with IHD and compared to stable patients with cardiovascular diseases other than IHD.

Methods

The study population was 2088 patients (1698 males and 390 females) who were admitted to our hospital due to IHD (n = 1,661) and non-IHD (n = 427) and underwent cardiac catheterization. Measurements of the hemodynamic parameters and blood sampling were performed.

Results

The plasma BNP levels were significantly lower in the IHD group than in the non-IHD group (p<0.001). The multiple regression analysis examining the logBNP values showed that age, a male gender, low left ventricular ejection fraction, low body mass index, serum creatinine, atrial fibrillation and IHD per se were significant explanatory variables. When the total study population was divided according to gender, the plasma BNP levels were found to be significantly lower in the IHD group than in the non-IHD group among males (p<0.001), but not females (p = NS). Furthermore, a multiple logistic regression analysis of IHD showed the logBNP value to be a significant explanatory variable in males (regression coefficient: −0.669, p<0.001), but not females (p = NS).

Conclusions

The plasma BNP levels were relatively low in stable patients with IHD compared with those observed in stable patients with non-IHD; this tendency was evident in males. Perhaps, the low reactivity of BNP is causally associated with IHD in males. We hope that this study will serve as a test of future prospective studies.     

Epidemiology of Functional Abdominal Bloating and Its Impact on Health Related Quality of Life: Male-Female Stratified Propensity Score Analysis in a Population Based Survey in Mainland China

Background

The epidemiology of Functional abdominal bloating (FAB) and its impact on health-related quality of life (HRQoL) in Chinese people remains unclear.

Methods

Randomised, stratified, multi-stage sampling methodology was used to select a representative sample of the general population from five cities in China (n = 16,078). All respondents completed the modified Rome II questionnaire; 20% were asked to complete the 36-item Short Form (SF-36). The associated factors of FAB were analyzed. The effects of FAB on HRQoL were estimated with gender stratification using propensity score techniques in 20% subsample.

Results

Overall, 643 individuals (4.00%) had FAB and it was more prevalent in males than in females (4.87% vs. 3.04%, P<0.001). For males, self-reported history of dyspepsia was most strongly associated with FAB (OR = 2.78; 95% CI: 1.59, 4.72). However, the most strongly associated factor was self-reported health status for females (moderate health vs. good health: OR = 2.06, 95% CI: 1.07, 3.96. P = 0.030; poor health vs. good health: OR = 5.71, 95% CI: 2.06, 15.09). Concerning HRQoL, FAB was found to be related to two domains: role limitation due to physical problems (P = 0.030) and bodily pain (P<0.001) in females. While, in males, there were significant differences in multiple domains between those with and without FAB.

Conclusion

The prevalence of FAB in China was lower than previous reports. Males who had ever been diagnosed with dyspepsia and females who were in a poor self-reported health status were correlated with a higher prevalence of FAB. FAB affected only physical health in females, but impaired both physical and mental health in males.     

Prevalence of Hypertension in Indian Tribes: A Systematic Review and Meta-Analysis of Observational Studies

Introduction

In India there is an increasing trend in hypertension prevalence among the general population. Studies have shown that tribal populations in India are also experiencing this burden.

Objective

The aim was to estimate the pooled prevalence of primary hypertension among adult tribal populations of India.

Methods

A systematic search was conducted in MEDLINE, IndMed, Web of Science, Google Scholar and major journals for studies published between 1981 and 2011. Two authors independently reviewed the studies, did quality assessment and extracted data in pre-coded spread-sheets. Pooled estimates of prevalence of hypertension were calculated using DerSimonian-Laird random effects model. Subgroup and sensitivity analyses and meta-regression were performed.

Results

Twenty studies or 53 subpopulations with 64 674 subjects were included in final review. The pooled estimate of hypertension prevalence was 16.1% (95% CI: 13.5, 19.2). There was significant heterogeneity among the studies (I² = 99% and Q = 4624.0, df  = 53, p<0.001). Subgroup analyses showed that year of study, acculturation status, special features, and BP measurement techniques significantly influenced prevalence, but after meta-regression analyses, ‘decade of study’ remained the only covariate that significantly and independently influenced prevalence (R² = 0.57, Q = 119.2, df  = 49, p value <0.001).

Conclusion

An increasing trend was found in the prevalence of hypertension in adult tribal populations across three decades. Although acculturation was probably the underlying agent that caused this increase, other unmeasured factors that need further research were also important. Concerned policy makers should focus on the changing health needs of tribal communities.     

Ecology driving genetic variation: a comparative phylogeography of jungle cat (Felis chaus) and leopard cat (Prionailurus bengalensis) in India

Background

Comparative phylogeography links historical population processes to current/ecological processes through congruent/incongruent patterns of genetic variation among species/lineages. Despite high biodiversity, India lacks a phylogeographic paradigm due to limited comparative studies. We compared the phylogenetic patterns of Indian populations of jungle cat (Felis chaus) and leopard cat (Prionailurus bengalensis). Given similarities in their distribution within India, evolutionary histories, body size and habits, congruent patterns of genetic variation were expected.

Methodology/Principal Findings

We collected scats from various biogeographic zones in India and analyzed mtDNA from 55 jungle cats (460 bp NADH5, 141 bp cytochrome b) and 40 leopard cats (362 bp NADH5, 202 bp cytochrome b). Jungle cats revealed high genetic variation, relatively low population structure and demographic expansion around the mid-Pleistocene. In contrast, leopard cats revealed lower genetic variation and high population structure with a F _ST of 0.86 between North and South Indian populations. Niche-model analyses using two approaches (BIOCLIM and MaxEnt) support absence of leopard cats from Central India, indicating a climate associated barrier. We hypothesize that high summer temperatures limit leopard cat distribution and that a rise in temperature in the peninsular region of India during the LGM caused the split in leopard cat population in India.

Conclusions/Significance

Our results indicate that ecological variables describing a species range can predict genetic patterns. Our study has also resolved the confusion over the distribution of the leopard cat in India. The reciprocally monophyletic island population in the South mandates conservation attention.     

The Plasmodium vivax Merozoite Surface Protein 3β Sequence Reveals Contrasting Parasite Populations in Southern and Northwestern Thailand

Background

Malaria control efforts have a significant impact on the epidemiology and parasite population dynamics. In countries aiming for malaria elimination, malaria transmission may be restricted to limited transmission hot spots, where parasite populations may be isolated from each other and experience different selection forces. Here we aim to examine the Plasmodium vivax population divergence in geographically isolated transmission zones in Thailand.

Methodology

We employed the P. vivax merozoite surface protein 3β (PvMSP3β) as a molecular marker for characterizing P. vivax populations based on the extensive diversity of this gene in Southeast Asian parasite populations. To examine two parasite populations with different transmission levels in Thailand, we obtained 45 P. vivax isolates from Tak Province, northwestern Thailand, where the annual parasite incidence (API) was more than 2%, and 28 isolates from Yala and Narathiwat Provinces, southern Thailand, where the API was less than 0.02%. We sequenced the PvMSP3β gene and examined its genetic diversity and molecular evolution between the parasite populations.

Principal Findings

Of 58 isolates containing single PvMSP3β alleles, 31 sequence types were identified. The overall haplotype diversity was 0.77±0.06 and nucleotide diversity 0.0877±0.0054. The northwestern vivax malaria population exhibited extensive haplotype diversity (HD) of PvMSP3β (HD = 1.0). In contrast, the southern parasite population displayed a single PvMSP3β allele (HD = 0), suggesting a clonal population expansion. This result revealed that the extent of allelic diversity in P. vivax populations in Thailand varies among endemic areas.

Conclusion

Malaria parasite populations in a given region may vary significantly in genetic diversity, which may be the result of control and influenced by the magnitude of malaria transmission intensity. This is an issue that should be taken into account for the implementation of P. vivax control measures such as drug policy and vaccine development.     

Tumor Necrosis Factor-A Polymorphisms and Colorectal Cancer Risk: A Meta-Analysis

Background and Objectives

Tumor necrosis factor-alpha (TNF-a) was related to inflammation and involved in the development of colorectal cancer. Polymorphisms located in TNF-a promoter region, such as 308G/A and 238G/A, could affect the risk of various types of cancer by regulating TNF-a production. In this study, a meta-analysis was performed to investigate the association between common polymorphisms of TNF-a promoter region and colorectal cancer susceptibility.

Methods

Searching of several databases was performed for all publications on the association between TNF-a polymorphisms and colorectal cancer. Summary odds ratios (ORs) with their 95% confidence intervals (95% CIs) were calculated using random-effects models. Stratified analyses based on ethnicity and control population source were also conducted.

Results

Overall, TNF-a 308A polymorphism showed a significant association with increased risk of colorectal cancer in worldwide populations under homozygote comparison [AA vs. GG, OR (95% CI) = 1.46 (1.07–1.97)] other than heterozygote comparison [AG vs. GG, OR (95% CI) = 1.05 (0.93–1.19)]. TNF-a 238A was not associated with colorectal cancer risk under homozygote or heterozygote comparisons. In stratified analysis, significant association was observed only in Western populations [AA vs. GG, OR (95% CI) = 1.39 (1.01–1.91)] other than in Eastern populations under homozygote comparison. No significant difference was observed between population-based subgroup and hospital-based subgroup.

Conclusions

TNF-a 308A was moderately associated with an increased risk of colorectal cancer in Western populations, and TNF-a 238A polymorphism was not significantly associated with colorectal cancer risk.     

Toxocara Seroprevalence among Clinically Healthy Individuals,Pregnant Women and Psychiatric Patients and Associated Risk Factors in Shandong Province,Eastern China

Background

Toxocarosis is a widespread zoonosis caused by the ascarid nematodes Toxocara canis and Toxocara cati, which primarily infect dogs and cats, respectively. Most human infections with Toxocara are asymptomatic; however, some infected individuals may develop a serious illness and even death. Nevertheless, epidemiological knowledge regarding the prevalence and risks associated with Toxocara infection is limited in China. Therefore, we performed a cross-sectional pilot study and estimated the seroprevalence of Toxocara infection in humans in Shandong Province, eastern China for the first time, from June 2011 to July 2013, involving clinically healthy individuals, pregnant women and psychiatric patients, aiming to attract public attention to Toxocara infection.

Methodology/Principle Findings

Seroprevalence of Toxocara was determined using an enzyme-linked immunosorbent assay based on a cross-sectional study conducted in Qingdao and Weihai, Shandong Province, eastern China. Factors potentially associated with Toxocara infection were identified by logistic regression analysis. The overall Toxocara seroprevalence among the study population (n = 2866) was 12.25%, and a significantly higher seroprevalence in psychiatric patients (16.40%, 73/445) than that in clinically healthy individuals (13.07%, 187/1431) and pregnant women (9.19%, 91/990) was revealed. Univariate analyses suggested that keeping dogs at home (OR = 0.06, 95% CI 0.05–0.08, P<0.001), contact with cats and dogs (OR = 0.42, 95% CI 0.33–0.53, P<0.001) and exposure with soil (OR = 0.37, 95% CI 0.28–0.49, P<0.001) were risk factors associated with Toxocara infection.

Conclusions/Significance

The present study revealed, for the first time, that human infection with Toxocara is common in eastern China, posing a significant public health concern. Increasing human and dog populations, population movements and climate change all will serve to increase the importance of this zoonosis. Further studies under controlled conditions are necessary to define potential morbidity associated with Toxocara infection.     

GNB3, eNOS,and Mitochondrial DNA Polymorphisms Correlate to Natural Longevity in a Xinjiang Uygur Population

Background

In centenarian populations, application of the positive biology approach (examination of positive phenotypes in aging) has revealed that mitochondrial DNA (mtDNA) mutation accumulation may be linked to human longevity; however, the role of guanine nucleotide-binding protein (G protein) abnormalities modulated by G-protein beta-3 (GNB3) and nitrate (NO2) production associated with endothelial nitric oxide synthase (eNOS), commonly appearing in age-related diseases, remains undetermined.

Objective

The association between the mtDNA 5178A/C, mtDNA 10398A/G, GNB3 C825T, and eNOS polymorphisms and longevity in a Uygur population (Xinjiang region, China) were investigated.

Methods

A total of 275 experimental subjects aged ≥100 or with 4 generations currently living were screened for inclusion in the centenarian (>100 years) and nonagenarian groups (90–100 years), and 112 65–70 year old control subjects were selected. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to examine mtDNA 5178A/C, mtDNA 10398A/G, GNB3 C825T, and eNOS. Associations between polymorphic loci, genotypes, and longevity were analyzed.

Results

165 included subjects (M∶F = 107∶58; mean age = 97±3 years; mean age 100–113 years) were assigned to the centenarian (M∶F = 46/19; n = 65) and nonagenarian groups (M∶F = 61/39; n = 100). Associations between mtDNA C5178A and A10398G polymorphisms with longevity in the centenarian group with mtDNA genotype frequencies 5178A and 10398G were 66.79% and 36.8%.

Conclusions

Applying the overwhelming longevity observed in Uygur populations, these findings demonstrate that mtDNA 5178A/C and 10398A/G, GNB3 C825T, and eNOS polymorphisms are useful as a genetic basis for longevity.     

Role of IL-4 Gene Polymorphisms in HBV-Related Hepatocellular Carcinoma in a Chinese Population

Background

Interleukin-4 (IL-4) is best known as an important mediator and modulator of immune and inflammatory responses. Hepatocellular carcinoma (HCC) is a typical inflammation-related cancer, and genetic variations in the IL-4 gene may be associated with the risk of hepatitis B virus (HBV)-related HCC. However, few studies have been conducted on their association.

Objectives

To clarify the effects of IL-4 gene polymorphisms on the risk of HBV-related HCC, two common variants, −590C/T (rs2243250) and −33C/T (rs2070874), and their relationship with HBV-related disease risk were investigated in a Chinese population.

Methods

IL-4 −590C/T and −33C/T polymorphisms were examined in 154 patients with HBV-related HCC, 62 patients with HBV-induced liver cirrhosis (LC), 129 patients with chronic hepatitis B (CHB), and 94 healthy controls, using the polymerase chain reaction-restriction fragment length polymorphism method and DNA sequencing.

Results

Overall, no significant differences were observed regarding the IL-4 −590C/T and −33C/T polymorphism genotypes, alleles, or haplotypes between the patient groups and the healthy controls. However, the CC genotypes of IL-4 −590C/T and −33C/T polymorphisms were observed to be significantly associated with CHB in subgroup analysis in males [CC versus TT (OR: 4.193, 95% CI: 1.094–16.071, P = 0.037; and OR: 3.438, 95% CI: 1.032–11.458, P = 0.044) and CC versus TT+CT (OR: 4.09, 95% CI: 1.08–15.49, P = 0.038; and OR: 3.43, 95% CI: 1.04–11.28, P = 0.042)].

Conclusions

These findings suggest that genetic variants in IL-4 −590C/T and −33C/T polymorphisms may be a risk factor for CHB in Chinese males but not for HBV-related LC or HCC.     

A Large Plasmodium vivax Reservoir and Little Population Structure in the South Pacific

Introduction

The importance of Plasmodium vivax in malaria elimination is increasingly being recognized, yet little is known about its population size and population genetic structure in the South Pacific, an area that is the focus of intensified malaria control.

Methods

We have genotyped 13 microsatellite markers in 295 P. vivax isolates from four geographically distinct sites in Papua New Guinea (PNG) and one site from Solomon Islands, representing different transmission intensities.

Results

Diversity was very high with expected heterozygosity values ranging from 0.62 to 0.98 for the different markers. Effective population size was high (12′872 to 19′533 per site). In PNG population structuring was limited with moderate levels of genetic differentiation. F _ST values (adjusted for high diversity of markers) were 0.14–0.15. Slightly higher levels were observed between PNG populations and Solomon Islands (F _ST = 0.16).

Conclusions

Low levels of population structure despite geographical barriers to transmission are in sharp contrast to results from regions of low P. vivax endemicity. Prior to intensification of malaria control programs in the study area, parasite diversity and effective population size remained high.     

Genetic Variants at 12p11 and 12q24 Are Associated with Breast Cancer Risk in a Chinese Population

Background

A recent genome-wide association study (GWAS) has identified three new breast cancer susceptibility loci at 12p11, 12q24 and 21q21 in populations of European descent. However, because of the genetic heterogeneity, it is largely unknown for the role of these loci in the breast cancer susceptibility in the populations of non-European descent.

Methodology/Principal Findings

Here, we genotyped three variants (rs10771399 at 12p11, rs1292011 at 12q24 and rs2823093 at 21q21) in an independent case–control study with a total of 1792 breast cancer cases and 1867 cancer-free controls in a Chinese population. We found that rs10771399 and rs1292011 were significantly associated with risk of breast cancer with per-allele odds ratios (ORs) of 0.85 (95% confidence interval (CI): 0.76–0.96; P = 0.010) and 0.84 (95% CI: 0.76–0.95; P = 4.50×10⁻³), respectively, which was consistent with those reported in populations of European descent. Similar effects were observed between ER/PR positive and negative breast cancer for both loci. However, we did not found significant association between rs2823093 and breast cancer risk (OR = 0.97, 95%CI = 0.76–1.24; P  = 0.795).

Conclusions/Significance

Our results indicate that genetic variants at 12p11 and 12q24 may also play an important role in breast cancer development in Chinese women.     

Multivariate Statistical Analyses Demonstrate Unique Host Immune Responses to Single and Dual Lentiviral Infection

Background

Feline immunodeficiency virus (FIV) and human immunodeficiency virus (HIV) are recently identified lentiviruses that cause progressive immune decline and ultimately death in infected cats and humans. It is of great interest to understand how to prevent immune system collapse caused by these lentiviruses. We recently described that disease caused by a virulent FIV strain in cats can be attenuated if animals are first infected with a feline immunodeficiency virus derived from a wild cougar. The detailed temporal tracking of cat immunological parameters in response to two viral infections resulted in high-dimensional datasets containing variables that exhibit strong co-variation. Initial analyses of these complex data using univariate statistical techniques did not account for interactions among immunological response variables and therefore potentially obscured significant effects between infection state and immunological parameters.

Methodology and Principal Findings

Here, we apply a suite of multivariate statistical tools, including Principal Component Analysis, MANOVA and Linear Discriminant Analysis, to temporal immunological data resulting from FIV superinfection in domestic cats. We investigated the co-variation among immunological responses, the differences in immune parameters among four groups of five cats each (uninfected, single and dual infected animals), and the “immune profiles” that discriminate among them over the first four weeks following superinfection. Dual infected cats mount an immune response by 24 days post superinfection that is characterized by elevated levels of CD8 and CD25 cells and increased expression of IL4 and IFNγ, and FAS. This profile discriminates dual infected cats from cats infected with FIV alone, which show high IL-10 and lower numbers of CD8 and CD25 cells.

Conclusions

Multivariate statistical analyses demonstrate both the dynamic nature of the immune response to FIV single and dual infection and the development of a unique immunological profile in dual infected cats, which are protected from immune decline.     

Salt-Restriction-Spoon Improved the Salt Intake among Residents in China

Objective

To evaluate the effect of an improved salt-restriction spoon on the attitude of salt-restriction, the using rate of salt-restriction-spoon, the actual salt intake, and 24-hour urinary sodium excretion (24HUNa).

Design

A community intervention study.

Setting

Two villages in Beijing.

Participants

403 local adult residents being responsible for home cooking.

Intervention

Participants were randomly assigned to the intervention group or the control group. Those in the intervention group were provided with an improved salt-restriction-spoon and health education, and were informed of their actual salt intake and 24HUNa. Not any intervention was given to those in the control group.

Main Outcome Measures

The scores on the variables of Health Belief Model, the using rate of salt-restriction-spoon, the actual salt intake, and 24HUNa.

Analysis

Covariance analyses, Chi-square tests, Student’s t tests, and repeated measures analyses of variance.

Results

After 6 months of intervention, the intervention group felt significantly less objective barriers, and got access to significantly more cues to action as compared to the control group. The using rate and the correctly using rate of salt-restriction-spoon were significantly higher in the intervention group. The daily salt intake decreased by 1.42 g in the intervention group and by 0.28 g in the control group, and repeated measures analysis of variance showed significant change over time (F = 7.044, P<0.001) and significant difference between groups by time (F = 2.589, P = 0.041). The 24HUNa decreased by 34.84 mmol in the intervention group and by 33.65 mmol in the control group, and repeated measures analysis of variance showed significant change over time (F = 14.648, P<0.001) without significant difference between groups by time (F = 0.222, P = 0.870).

Conclusions

The intervention effect was acceptable, therefore, the improved salt-restriction-spoon and corresponding health education could be considered as an alternative for salt reduction strategy in China and other countries where salt intake comes mainly from home cooking.     

Genetic Association Study betweenSTK39 and CCDC62/HIP1R and Parkinson’s Disease

Background

The first large-scale meta-analysis of published genome-wide association studies (GWAS) in Parkinson’s disease (PD) identified 5 new genetic loci (ACMSD, STK39, MCCC1/LAMP3, SYT11, and CCDC62/HIP1R). Very recently, a large-scale replication and heterogeneity study also reported that STK39 and CCDC62/HIP1R increased risk of PD in Asian and Caucasian populations. However, their roles still remain unclear in a Han Chinese population from mainland China.

Methods

We examined genetic associations of STK39 rs2102808 and CCDC62/HIP1R rs12817488 with PD susceptibility in a Han Chinese population of 783 PD patients and 725 controls. We also performed further stratified analyses by the age of onset and accomplished in-depth clinical characteristics analyses between the different genotypes for each locus.

Results

No significant differences were observed in the minor allele frequency (MAF) among cases and controls at the two loci (STK39 rs2102808: OR = 1.06, 95% CI = 0.91, 1.23, P = 0.467; CCDC62/HIP1R rs12817488: OR = 0.88, 95% CI = 0.76, 1.01, P = 0.072). Subgroup analyses by the age of onset also showed no significant differences among different subgroups of the two loci. In addition, minor allele carriers cannot be distinguished from non-carriers based on their clinical features at the two loci.

Conclusions

We are unable to demonstrate the association between STK39 and CCDC62/HIP1R and PD susceptibility in a Han Chinese population from mainland China. Additional replication studies in other populations and functional studies are warranted to better validate the role of the two new loci in PD risk.     

Role of HLA-DP Polymorphisms on Chronicity and Disease Activity of Hepatitis B Infection in Southern Chinese

Background and Aims

The association between HLA-DP single nucleotide polymorphisms (SNPs) and chronic hepatitis B virus (HBV) infection varies between different populations. We aimed to study the association between HLA-DP SNPs and HBV infection and disease activity in the Chinese population of Hong Kong.

Methods

We genotyped SNPs rs3077 (near HLA-DPA1) and rs9277378 and rs3128917 (both near HLA-DPB1) in 500 HBV carriers (hepatitis B surface antigen [HBsAg]-positive), 245 non-HBV infected controls (HBsAg- and antibody to hepatitis B core protein [anti-HBc]-negative), and 259 subjects with natural HBV clearance (HBsAg-negative, anti-HBc-positive). Inactive HBV carriers state was defined by HBV DNA levels <2,000 IU/ml and persistently normal alanine aminotransferase level for least 12 months.

Results

Compared to the non-HBV infected subjects, the HBV carriers had a significantly lower frequency of the rs3077 T allele (p = 0.0040), rs9277378 A allele (p = 0.0068) and a trend for lower frequency of rs3128917 T allele (p = 0.054). These alleles were associated with an increased chance of HBV clearance (rs3077: OR = 1.41, p = 0.0083; rs9277378: OR = 1.61, p = 0.00011; rs3128917: OR = 1.54, p = 0.00017). Significant associations between HLA-DP genotypes and HBV clearance were also found under different genetic models. Haplotype TAT was associated with an increased chance of HBV clearance (OR = 1.64, p = 0.0013). No association was found between these SNPs and HBV disease activity.

Conclusion

HLA-DP SNPs rs3077, rs9277378 and rs3128917 were associated with chronicity of HBV disease in the Chinese. Further studies are required to determine whether these SNPs influence the disease endemicity in different ethnic populations.     

Association Study on ADAM33 Polymorphisms in Mite-Sensitized Persistent Allergic Rhinitis in a Chinese Population

Background

The ADAM33 gene has been identified as a potentially important asthma candidate gene and polymorphisms in this gene have been shown to be associated with asthma and seasonal allergic rhinitis.

Objective

To assess whether the ADAM33 polymorphisms are associated with persistent allergic rhinitis (PER) due to house dust mites in a Chinese population.

Methods

In a hospital-based case-control study of 515 patients with mite-sensitized PER and 495 healthy controls, we genotyped seven single nucleotide polymorphisms (SNPs) in ADAM33. Serum levels of eosinophil cationic protein, total IgE and allergen-specific IgE against Dermatophagoides pteronyssinus and Dermatophagoides farinae were measured by the ImmunoCAP assays.

Results

In the single-locus analysis, three polymorphisms, rs3918392 (F1), rs528557 (S2) and rs2787093, were significantly associated with mite-sensitized PER. SNP S2 was associated with significantly increased risk both of asthmatic and nonasthmatic mite-sensitized PER. In the combined genotypes analysis, individuals with 2–4 risk alleles had a significantly higher risk of mite-sensitized PER (adjusted OR = 1.99, 95% CI = 1.50–2.62) than those with 0–1 risk alleles. Haplotype-based association analysis revealed that the ACAGCCT haplotype might have potential to protect against mite-sensitized PER (adjusted OR = 0.67; 95% CI = 0.49–0.90).

Conclusions

Polymorphisms in the ADAM33 gene may contribute to susceptibility of mite-sensitized PER in this Chinese population.