Family-based association study of ZNF533, DOCK4 and IMMP2L gene polymorphisms linked to autism in a northeastern Chinese Han population简

Objective

A study in a Caucasian population has identified two single-nucleotide polymorphisms (SNPs) in ZNF533, one in DOCK4, and two in IMMP2L, which were all significantly associated with autism. They are located in AUTS1 and AUTS5, which have been identified as autism susceptibility loci in several genome-wide screens. The present study aimed to investigate whether ZNF533, DOCK4, and IMMP2L genes are also associated with autism in a northeastern Chinese Han population.

Methods

We performed a similar association study using families with three individuals (one autistic child and two unaffected parents). A family-based transmission disequilibrium test (TDT) was used to analyze the results.

Results

There were significant associations between autism and the two SNPs of ZNF533 gene (rs11885327: χ ²=4.5200, P=0.0335; rs1964081: χ ²=4.2610, P=0.0390) and the SNP of DOCK4 gene (rs2217262: χ ²=5.3430, P=0.0208).

Conclusions

Our data suggest that ZNF533 and DOCK4 genes are linked to a predisposition to autism in the northeastern Chinese Han population.     

XRCC1 Arg399Gln and clinical outcome of platinum-based treatment for advanced non-small cell lung cancer: a meta-analysis in 17 studies

Objective: XRCC1 polymorphism is a research hotpot in individual treatment for non-small cell lung cancer (NSCLC). To obtain the association between XRCC1 polymorphism and clinical outcome of platinum-based treatment for NSCLC, a meta-analysis was conducted. Methods: Databases including PubMed, Embase, Cochrane, and Chinese National Knowledge Infrastructure (CNKI) were searched for publications that met the inclusion criteria. A fixed effect model was used to estimate pooled odds ratio (OR) and hazard ratio (HR) with 95% confidence interval (CI) for the association between XRCC1 Arg399Gln and response or survival of platinum-based treatment for advanced NSCLC. A chi-squared-based Q-test was used to test the heterogeneity hypothesis. Egger’s test was used to check publication bias. Results: Seventeen published case-control studies that focus on the association between XRCC1 Arg399Gln and response or survival of platinum-based treatment for advanced NSCLC in 2 256 subjects were included in this meta-analysis, of whom 522 were AA genotypes (23.2% frequency), 916 AG genotypes (40.6% frequency), and 818 GG genotypes (36.2% frequency). The overall response rate (ORR) was 45.2% (110/243) for AA genotype patients, 29.9% for AG genotype (73/244), and 30.7% for GG genotype (124/403). The heterogeneity test did not show any heterogeneity and the Egger’s test did not reveal an obvious publication bias among the included studies. The meta-analysis indicated that AA genotype patients presented higher response rates toward platinum drug treatment compared with G model (GG+GA) patients (GG vs. AA model: OR=0.489, 95% CI 0.266–0.900, P=0.021; AG vs. AA model: OR=0.608, 95% CI 0.392–0.941, P=0.026; GA+AA vs. GG model: OR=1.259, 95% CI 0.931–1.701, P=0.135; GG+GA vs. AA model: OR=0.455, 95% CI 0.313–0.663, P=0.0001). However, no evidence validates XRCC1 associates with the survival following platinum drug therapy. Conclusions: Our meta-analysis suggested that XRCC1 Arg399Gln is related with the sensitivity of NSCLC patients to platinum-based treatment. AA genotype patients present more desirable curative effectiveness compared with other patients.     

Investigation of the association between all-trans-retinol dehydrogenase (RDH8) polymorphisms and high myopia in Chinese

Retinoic acid level in the retina/choroid is altered in induced myopia models. All-trans-retinol dehydrogenase (RDH8) is an important enzyme of retinoic acid metabolism. This study aimed to investigate the association of the RDH8 gene with high myopia. Three single nucleotide polymorphisms (SNPs) [RDH851 (rs2233789), RDH8E5a (rs1644731), and RDH855b (rs3760753)] were selected, based on the linkage disequilibrium pattern of RDH8 from a previous study, and genotyped for 160 Han Chinese nuclear families with highly myopic (−10 diopters or worse) offspring as well as in an independent group with 166 highly myopic cases (−10 diopters or worse) and 211 controls. Family-based association analysis was performed using the family-based association test (FBAT) package, and genotype relative risk (GRR) was calculated using the GenAssoc program. Population-based association analysis was performed using Chi-square test. These SNPs were in linkage equilibrium with each other. SNPs RDH851 (rs2233789) and RDH8E5a (rs1644731) both did not show association with high myopia. SNP RDH855b (rs3760753) demonstrated significant association (P=0.0269) with a GRR of 0.543 (95% confidence interval=0.304–0.968, P=0.038). The association became statistically insignificant, however, after multiple comparison correction. Haplotype analysis did not show a significant association either. Population-based association analysis also showed no significant association (P>0.05). Our family- and population-based data both suggest that the RDH8 gene is unlikely to be associated with high myopia in Chinese.     

Meta-analysis of <Emphasis Type="Italic">C242T</Emphasis> polymorphism in <Emphasis Type="Italic">CYBA</Emphasis> genes: risk of acute coronary syndrome is lower in Asians but not in Caucasians

Background

A lot of studies have demonstrated that C242T polymorphism in CYBA genes may play an important role in the pathological process of acute coronary syndrome (ACS). However, the results are not consistent. To further evaluate this debate, we performed a meta-analysis to determine the relationship between C242T polymorphism and ACS.

Methods and results

We screened PubMed/MEDLINE, EBSCIO, and EMBASE research reports until Mar. 2014 and extracted data from 10 studies involving 6102 ACS patients and 8669 controls. Subgroup analysis by ethnicity documented a significant decreased risk of ACS for C242T polymorphism in the Asian population under allelic comparison (odd ratio (OR) 0.73; 95% confidence intervals (CI) 0.64–0.83), dominant model (OR 0.71; 95% CI 0.62–0.82), and homozygote comparison (OR 0.57; 95% CI 0.35–0.92). However, in the overall population and especially with Caucasians, no significant association was uncovered. Further meta-regression analysis revealed that the heterogeneity among studies was largely attributed to ethnicity. No publication bias was detected through a funnel plot and an Egger’s linear regression test.

Conclusions

Taken together, our results suggest that the C242T polymorphism might be a protective factor against developing ACS in the Asian population. Further researches will be needed to identify the confounding factors which modified the protective effect of T allele among Caucasians.

     

Controversial opinion: evaluation of <Emphasis Type="Italic">EGR1</Emphasis> and <Emphasis Type="Italic">LAMA2</Emphasis> loci for high myopia in Chinese populations

Functional studies have suggested the important role of early growth response 1 (EGR1) and Laminin α2-chain (LAMA2) in human eye development. Genetic studies have reported a significant association of the single nucleotide polymorphism (SNP) in the LAMA2 gene with myopia. This study aimed to evaluate the association of the tagging SNPs (tSNPs) in the EGR1 and LAMA2 genes with high myopia in two independent Han Chinese populations. Four tSNPs (rs11743810 in the EGR1 gene; rs2571575, rs9321170, and rs1889891 in the LAMA2 gene) were selected, according to the HapMap database (http://hapmap.ncbi.nlm.nih.gov), and were genotyped using the ligase detection reaction (LDR) approach for 167 Han Chinese nuclear families with extremely highly myopic offspring (<?10.0 diopters) and an independent group with 485 extremely highly myopic cases (<?10.0 diopters) and 499 controls. Direct sequencing was used to confirm the LDR results in twenty randomly selected subjects. Family-based association analysis was performed using the family-based association test (FBAT) software package (Version 1.5.5). Population-based association analysis was performed using the Chi-square test. The association analysis power was estimated using online software (http://design.cs.ucla.edu). The FBAT demonstrated that all four tSNPs tested did not show association with high myopia (P>0.05). Haplotype analysis of tSNPs in the LAMA2 genes also did not show a significant association (P>0.05). Meanwhile, population-based association analysis also showed no significant association results with high myopia (P>0.05). On the basis of our family- and population-based analyses for the Han Chinese population, we did not find positive association signals of the four SNPs in the LAMA2 and EGR1 genes with high myopia.     

Correlation analysis of gene polymorphisms and β-lactam allergy

A total of 64 patients with β-lactam allergy and 30 control subjects were enrolled in a case-control study. This study is aimed to analyze the relationship between β-lactam allergy and 10 single nucleotide polymorphisms (SNPs) in interleukin-10 (IL-10), IL-13, IL-4Rα, high-affinity immunoglobulin E-receptor β chain (FcεRIβ), interferon γ receptor 2 (IFNGR2), and CYP3A4, and within the Han Chinese population of Northwest China. Genotyping for the SNPs was conducted using the Sequenom MassARRAY®platform. SPSS 17.0 was employed to analyze the statistical data and SHEsis was used to perform the haplotype reconstruction and analyze linkage disequilibrium of SNPs of IL-10 and IL-13. The results showed that the genotype distribution of CYP3A4 rs2242480/CT differed significantly between case and control groups of males (P=0.022; odds ratio (OR)=0.167, 95% confidence interval (CI): 0.032–0.867). Further analysis showed that CCA, CCG, and TAA haplotypes of IL-10 had no significant correlation in patients with β-lactam allergy. The correlation between CCT and CAC haplotypes of IL-13 and β-lactam allergy needs to be further studied. The analysis did not reveal any differences in the distribution of others gene polymorphisms between cases and controls.     

HER-2 overexpression and survival in colorectal cancer: a meta-analysis

Objective

Numerous studies examining the relationship between human epidermal growth factor receptor 2 (HER-2) overexpression and survival in patients with colorectal cancer (CRC) have yielded controversial results. We therefore performed a meta-analysis more precisely to estimate its prognostic value.

Methods

Published studies investigating the effect of HER-2 overexpression on CRC survival were identified; the hazard ratios (HRs) and their corresponding 95% confidence intervals (95% CIs) were pooled in terms of disease-specific or overall survival.

Results

Eleven studies were included in the meta-analysis. The pooled data showed that HER-2 overexpression was negatively related to CRC survival (HR=1.10, 95% CI: 0.77–1.44). Subgroup analyses regarding test method and study quality also demonstrated little association between HER-2 overexpression and CRC survival (HR=0.89, 95% CI: 0.50–1.29; HR=0.90, 95% CI: 0.43–1.37, respectively).

Conclusions

Regardless of several limitations, our study suggested that HER-2 overexpression probably had little impact on CRC survival.     

Child maltreatment and risk patterns among participants in a child abuse prevention program

The relationship between risk factors and Child Protective Services (CPS) outcomes in families who participate in home visiting programs to prevent abuse and neglect and who are reported to CPS is largely unknown. We examined the relationship between parental risk factors and the substantiation status and number of CPS reports in families in a statewide prevention program. We reviewed CPS reports from 2006 to 2008 for families in Connecticut's child abuse prevention program. Six risk factors (histories of CPS, domestic violence [DV], mental health, sexual abuse, substance abuse, and criminal involvement) and the number of caregivers were abstracted to create risk scores for each family member. Maltreatment type, substantiation, and number of reports were recorded. Odds ratios were calculated. Of 1,125 families, 171 (15.6%) had at least one CPS report, and reports of 131 families were available for review. Families with a substantiated (25.2%) versus unsubstantiated (74.8%) first report had a high number of paternal risk factors (OR = 6.13, 95% CI [1.89, 20.00]) and were more likely to have a history of maternal DV (OR = 8.47, 95% CI [2.96, 24.39]), paternal DV (OR = 11.23, 95% CI [3.33, 38.46]), and maternal criminal history (OR = 4.55; 95% CI [1.32, 15.60]). Families with >1 report (34.4%) versus 1 report (65.6%) were more likely to have >3 caregivers, but this was not statistically significant (OR = 2.53, 95% CI [0.98, 6.54]). In a prevention program for first-time families, DV, paternal risk, maternal criminal history, and an increased number of caregivers were associated with maltreatment outcomes. Targeting parental violence may impact child abuse prevention.     

Association of matrix metalloproteinase-9 C1562T polymorphism and coronary artery disease: a meta-analysis简

Objective

Many investigations have studied the associations between matrix metalloproteinase-9 (MMP-9) C1562T polymorphisms and coronary artery disease (CAD). However, the conclusions of these studies were inconsistent. Therefore, this study was aimed at clarifying the association between MMP-9 C1562T polymorphisms and CAD in a large-scale meta-analysis.

Methods

The PubMed and Embase databases were retrieved to collect all publications on the association between MMP-9 C1562T polymorphisms and CAD. Then the odd ratios (ORs) and 95% confidence intervals (95% CIs) for C1562T TT+TC versus CC genotype between CAD and the control groups were evaluated. Subgroup analysis was also performed according to different races. The meta-analysis was performed by Stata 10.0.

Results

Sixteen case-control studies were included in our meta-analysis, involving 11 032 CAD patients and 4628 non-CAD controls. Compared with C allele carriers, East Asian T allele carriers TT+TC had a significantly higher risk of CAD (OR=1.43; 95% CI: 1.03–1.99; P=0.031); however, there were no significant associations in Western populations (OR=1.06; 95% CI: 0.96–1.18; P=0.240) or West Asians (OR=1.13; 95% CI: 0.75–1.70; P=0.565). When further analyzing the association between C1562T polymorphisms and myocardial infarction (MI, the most serious type of CAD), the risk of TT+TC genotype versus CC genotype for MI was significantly higher for the overall (OR=1.21; 95% CI: 1.04–1.40; P=0.012) and for East Asians (OR=1.58; 95% CI: 1.26–1.97; P=0.000) but not in Western populations (OR=1.12; 95% CI: 0.99–1.26; P=0.078).

Conclusions

Our meta-analysis suggested an obvious ethnic difference in the association between MMP-9 C1562T polymorphisms and CAD. MMP-9 C1562T polymorphism was significantly related to CAD in East Asians. However, no significant associations were observed in either West Asians or Western populations.     

Partial AZFc duplications not deletions are associated with male infertility in the Yi population of Yunnan Province, China

Objective: There are many reports on associations between spermatogenesis and partial azoospermia factor c (AZFc) deletions as well as duplications; however, results are conflicting, possibly due to differences in methodology and ethnic background. The purpose of this study is to investigate the association of AZFc polymorphisms and male infertility in the Yi ethnic population, residents within Yunnan Province, China. Methods: A total of 224 infertile patients and 153 fertile subjects were selected in the Yi ethnic population. The study was performed by sequence-tagged site plus/minus (STS+/−) analysis followed by gene dosage and gene copy definition analysis. Y haplotypes of 215 cases and 115 controls were defined by 12 binary markers using single nucleotide polymorphism on Y chromosome (Y-SNP) multiplex assays based on single base primer extension technology. Results: The distribution of Y haplotypes was not significantly different between the case and control groups. The frequencies of both gr/gr (7.6% vs. 8.5%) and b2/b3 (6.3% vs. 8.5%) deletions do not show significant differences. Similarly, single nucleotide variant (SNV) analysis shows no significant difference of gene copy definition between the cases and controls. However, the frequency of partial duplications in the infertile group (4.0%) is significantly higher than that in the control group (0.7%). Further, we found a case with sY1206 deletion which had two CDY1 copies but removed half of DAZ genes. Conclusions: Our results show that male infertility is associated with partial AZFc duplications, but neither gr/gr nor b2/b3 deletions, suggesting that partial AZFc duplications rather than deletions are risk factors for male infertility in Chinese-Yi population.     

Adult mental health outcomes of child sexual abuse survivors born at extremely low birth weight

The high prevalence of child sexual abuse (CSA) is concerning, particularly as survivors are at increased risk for multiple adverse outcomes, including poor mental health across the lifespan. Children born at an extremely low birth weight (ELBW; <1000 g) and who experience CSA may be a group that is especially vulnerable to psychopathology later in life. However, no research has considered the mental health risks associated with being born at ELBW and experiencing CSA. In this study, we investigated the mental health of 179 ELBW survivors and 145 matched normal birth weight (NBW; >2500 g) participants at ages 22–26 and 29–36. At age 22–26, CSA was associated with increased odds of clinically significant internalizing (OR = 7.32, 95% CI: 2.31–23.23) and externalizing (OR = 4.65, 95% CI: 1.11–19.51) problems among ELBW participants exposed to CSA compared to those who did not, though confidence intervals were wide. At age 29–36, CSA was linked to increased odds of any current (OR = 3.43, 95% CI: 1.08–10.87) and lifetime (OR = 7.09, 95% CI: 2.00–25.03) non-substance use psychiatric disorders, however, this did not hold after adjustment for covariates. Statistically significant differences in mental health outcomes were not observed in NBW participants exposed to CSA compared to NBW participants who were not exposed. Survivors of significant perinatal adversity who are also exposed to CSA may be at higher risk for psychopathology through the fourth decade of life.     

Obesity prevalence among youth investigated for maltreatment in the United States

The objective of this study is to determine the prevalence and correlates of obesity among youth investigated for maltreatment in the United States. Participants were drawn from the National Survey of Child and Adolescent Well-Being II, a national probability study of 5,873 children aged birth to 17 years under investigation for maltreatment in 2008. From child weight reported by caregivers, we estimated obesity (weight-for-age ≥95th percentile) prevalence among children aged 2 through 17 (n = 2,948). Sex-specific logistic regression models by developmental age were used to identify obesity risk factors, including child age, race/ethnicity, and maltreatment type. Obesity prevalence was 25.4% and was higher among boys than girls (30.0% vs. 20.8%). African American adolescent boys had a lower risk for obesity than white boys (OR = 0.28, 95% CI [0.08, 0.94]). Compared with girls aged 2–5 with a neglect allegation, girls with a sexual abuse allegation were at greater risk for obesity (OR = 3.54, 95% CI [1.01, 12.41]). Compared with adolescent boys with a neglect allegation, boys with a physical abuse allegation had a lower risk for obesity (OR = 0.24, 95% CI [0.06, 0.99]). Adolescent girls with a prior family history of investigation were at greater risk for obesity than those without a history of investigation (OR = 3.97, 95% CI [1.58, 10.02]). Youth investigated for maltreatment have high obesity rates compared with national peers. Opportunities to modify and evaluate related child welfare policies and health care practices should be pursued.     

Serum lipids and other risk factors for diabetic retinopathy in Chinese type 2 diabetic patients

Objective

To investigate the association of serum lipids and other risk factors with diabetic retinopathy (DR) in Chinese type 2 diabetic patients.

Methods

Five hundred and twenty-three type 2 diabetic patients underwent ophthalmic examination by experienced retinal specialists to assess their DR. Serum lipids, including triglycerides, total cholesterol, high density lipoprotein cholesterol (HDLC), and low density lipoprotein cholesterol (LDLC), were measured using Roche automated clinical chemistry analyzers. The concentration of very low density lipoprotein cholesterol (VLDLC) was calculated based on total cholesterol, HDLC and LDLC. Hyperlipidemia was defined as a total cholesterol concentration of 6.2 mmol/L or higher or the use of lipid-lowering medications. The association of risk factors with any DR or proliferative diabetic retinopathy (PDR) was assessed using the odds ratio (OR) and its 95% confidence interval (CI), calculated from logistic regression models.

Results

In multivariate logistic regression models, hyperlipidemia (OR=2.39, 95% CI: 1.02–5.66), higher VLDLC (OR=1.59, 95% CI: 1.14–2.23), and higher triglyceride (OR=1.18, 95% CI: 1.03–1.37) were associated with increased risk of DR. A longer diabetic duration was associated with increased risk of DR (P<0.0001) and PDR (P=0.002) in a dose-response manner. Higher systolic blood pressure (P=0.02) and higher serum creatinine (P=0.01) were independently associated with increased risk of DR, and female gender was associated with increased risk of PDR (P=0.03).

Conclusions

Among Chinese type 2 diabetic patients, hyperlipidemia, higher VLDLC, and higher triglyceride were independently associated with increased risk of DR, suggesting control of serum lipids may decrease the risk of DR.     

Microcalorimetry studies of the antimicrobial actions of Aconitum alkaloids

The metabolic activity of organisms can be measured by recording the heat output using microcalorimetry. In this paper, the total alkaloids in the traditional Chinese medicine Radix Aconiti Lateralis were extracted and applied to Escherichia coli and Staphylococcus aureus. The effect of alkaloids on bacteria growth was studied by microcalorimetry. The power-time curves were plotted with a thermal activity monitor (TAM) air isothermal microcalorimeter and parameters such as growth rate constant (μ), peak-time (T_m), inhibitory ratio (I), and enhancement ratio (E) were calculated. The relationships between the concentration of Aconitum alkaloids and μ of E. coli or S. aureus were discussed. The results showed that Aconitum alkaloids had little effect on E. coli and had a potentially inhibitory effect on the growth of S. aureus.     

Haplotype of platelet receptor <Emphasis Type="Italic">P2RY12</Emphasis> gene is associated with residual clopidogrel on-treatment platelet reactivity

Objective

To investigate a possible association between common variations of the P2RY12 and the residual clopidogrel on-treatment platelet reactivity after adjusting for the influence of CYP2C19 tested by thromboelastography (TEG).

Methods

One hundred and eighty patients with acute coronary syndrome (ACS) treated with clopidogrel and aspirin were included and platelet function was assessed by TEG. Five selected P2RY12 single nucleotide polymorphisms (SNPs; rs6798347, rs6787801, rs6801273, rs6785930, and rs2046934), which cover the common variations in the P2RY12 gene and its regulatory regions, and three CYP2C19 SNPs (^*2,^*3,^*17) were genotyped and possible haplotypes were analyzed.

Results

The high on-treatment platelet reactivity (HTPR) prevalence defined by a platelet inhibition rate <30% by TEG in adenosine diphosphate (ADP)-channel was 69 (38.33%). Six common haplotypes were inferred from four of the selected P2RY12 SNPs (denoted H₀ to H₅) according to the linkage disequilibrium R square (except for rs2046934). Haplotype H₁ showed a significantly lower incidence of HTPR than the reference haplotype (H₀) in the total study population while haplotypes H₁ and H₂ showed significantly lower incidences of HTPR than H₀ in the nonsmoker subgroup after adjusting for CYP2C19 effects and demographic characteristics. rs2046934 (T744C) did not show any significant association with HTPR.

Conclusions

The combination of common P2RY12 variations including regulatory regions rather than rs2046934 (T744C) that related to pharmacodynamics of clopidogrel in patients with ACS was independently associated with residual on-clopidogrel platelet reactivity. This is apart from the established association of the CYP2C19. This association seemed more important in the subgroup defined by smoking.

     

Diet and Pregnancy: Health-Care Providers and Patient Behaviors

In this study, associations between health-care providers (HCPs) discussing diet with their pregnant patients and patient dietary behavior were assessed in addition to factors related to HCPs discussing diet with their patients. Questionnaires were completed by 237 pregnant women and 31 HCPs at 12 obstetrics–gynecology clinics across the United States. Patients provided versus those not provided dietary counseling by their HCP were more likely (OR = 2.17, 95%; CI = 0.75–6.25) to engage in healthy dietary practices. HCPs that discussed multiple health behaviors were nearly four times more likely to discuss diet with their pregnant patients compared with HCP who did not discuss other health behaviors (OR = 3.67, 95%; CI = 1.10–12.28). This study indicates that HCP education can positively impact dietary behaviors of their pregnant patients.     

Adolescent psychosocial factors and participation in education and employment in young adulthood: A systematic review and meta-analyses

Adolescence is a critical period for successful transition into adulthood. This systematic review of empirical longitudinal evidence investigated the associations between adolescent psychosocial factors and education and employment status in young adulthood. Five electronic databases (MEDLINE, PsycINFO, CINAHL, ASSIA and ERIC) were searched. Meta-analysis was conducted by using odds ratios (OR) as our common effect size; a narrative synthesis of results was also completed. Of the 8970 references screened, 14 articles were included and mapped into seven domains, namely, behavioral problems, peer problems, substance use, prosocial skills, self-evaluations, aspirations and physical activity. The results showed that behavioral problems (overall OR: 1.48; 95% CI: 1.26–1.74) and peer problems (overall OR_adj: 1.27; 95% CI: 1.02–1.57) were significantly associated with being out of education, employment and training (NEET) as young adults. Prosocial skills did not present a significant association (overall OR: 1.03; 95% CI: 0.92–1.15). Other domains were narratively synthesized. The role of substance use was less clear. Only a few studies were available for self-evaluations, aspirations and physical activity domains. Implications for research and practice are discussed.