Angiotensin-converting-enzyme gene polymorphism and heart failure: a case–control study

Heart failure (HF) is the final outcome of virtually all cardiovascular diseases and is a major and increasingly serious public health problem. The renin–angiotensin system plays an important role in the pathogenesis of cardiovascular disease. Insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) has attracted significant attention; it has been extensively investigated in a spectrum of cardiovascular phenotypes because of its correlation with serum ACE activity. There is controversy regarding the association of ACE I/D polymorphism with cardiovascular disease. The aim of this study was to investigate whether ACE genotype is associated with HF by comparing cases and controls. The study sample consisted of 229 cases with HF due to coronary heart disease or idiopathic dilated cardiomyopathy and 230 controls recruited from the general population. The ACE I/D genotype was identified using a polymerase chain reaction assay. No evidence was found to support an association between ACE genotype and HF.     

Biomarkers of pulmonary hypertension in patients with scleroderma: a case–control study

IntroductionSignificant pulmonary vascular disease is a leading cause of death in patients with scleroderma, and early detection and early medical intervention are important, as they may delay disease progression and improve survival and quality of life. Although several biomarkers have been proposed, there remains a need to define a reliable biomarker of early pulmonary vascular disease and subsequent development of pulmonary hypertension (PH). The purpose of this study was to define potential biomarkers for clinically significant pulmonary vascular disease in patients with scleroderma.MethodsThe circulating growth factors basic fibroblast growth factor, placental growth factor (PlGF), vascular endothelial growth factor (VEGF), hepatocyte growth factor, and soluble VEGF receptor 1 (sFlt-1), as well as cytokines (interleukin [IL]-1β IL-2, IL-4, IL-5, IL-8, IL-10, IL-12, IL-13, tumor necrosis factor-α, and interferon-γ), were quantified in patients with scleroderma with PH (n = 37) or without PH (n = 40). In non-parametric unadjusted analyses, we examined associations of growth factor and cytokine levels with PH. In a subset of each group, a second set of earlier samples, drawn 3.0±1.6 years earlier, were assessed to determine the changes over time.ResultssFlt-1 (p = 0.02) and PlGF (p = 0.02) were higher in the PH than in the non-PH group. sFlt-1 (ρ = 0.3245; p = 0.01) positively correlated with right ventricular systolic pressure. Both PlGF (p = 0.03) and sFlt-1 (p = 0.04) positively correlated with the ratio of forced vital capacity to diffusing capacity for carbon monoxide (DLCO), and both inversely correlated with DLCO (p = 0.01). Both PlGF and sFlt-1 levels were stable over time in the control population.ConclusionsOur study demonstrated clear associations between regulators of angiogenesis (sFlt-1 and PlGF) and measures of PH in scleroderma and that these growth factors are potential biomarkers for PH in patients with scleroderma. Larger longitudinal studies are required for validation of our results.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-015-0712-4) contains supplementary material, which is available to authorized users.     

HTERT MNS16A polymorphism in breast cancer: a case–control study

This case–control study aims to investigate the role of HTERT MNS16A polymorphism as a potential risk factors and/or a prognostic marker for breast cancer. 113 consecutive incident cases of histologically confirmed ductal breast cancer and 124 healthy controls were recruited. HTERT MNS16A polymorphism was genotyped (L: long allele, S: short allele); multivariate logistic regression was performed. No significant association was noted either at the overall analysis (OR?=?1.57, 95?% CI 0.84–2.93 for heterozygous LS carriers; OR?=?1.02, 95?% CI 0.54–1.95 for homozygous SS carriers) or at the subanalyses in premenopausal and postmenopausal women. With respect to survival analysis, HTERT MNS16A polymorphism was not associated with either disease-free survival or overall survival. HTERT MNS16A polymorphism does not seem to be a risk factor for breast cancer in the Caucasian Greek population. Further, larger studies from other countries and subjects seem to be needed as this novel polymorphism is being examined in depth.     

Carcinogen DNA adducts and the risk of colon cancer: case–control study

Colorectal cancer represents 8.5% of all tumours at the King Faisal Specialist Hospital & Research Centre. Environmental and dietary carcinogens such as polycyclic aromatic hydrocarbons (PAHs) and heterocyclic amines (HCAs) have long been suspected to play a prominent role in colon cancer aetiology. We designed a case–control study to test the hypothesis of whether or not the presence of DNA adducts can play a role in the aetiology of colon cancer. DNA adducts were measured in 24 cancerous and 20 non-cancerous tissue samples of newly diagnosed colon cancer patients by ³²P-post-labelling technique. Normal tissue from 19 hospital patients served as controls. The mean levels of adducts per 10¹⁰ nucleotides in cancerous and non-cancerous tissue were 151.75±217.27 and 114.81±186.10, respectively; however, only adducts in cancerous tissue were significantly higher than controls (32.78±57.51 per 10¹⁰ nucleotides) with p-values of 0.017. No BPDE-DNA adducts were found. No relationship was found between urinary cotinine as a marker of tobacco smoke and 1-hydroxypyrene as an indicator of an individual's internal dose of PAHs and DNA adducts. In a logistic regression model, only adducts in cancerous tissue were associated with the subsequent risk of colon cancer, with an odds ratio of 3.587 (95% confidence interval 0.833–15.448) after adjustment for age and the duration of living in the current region, but of a borderline significance (p=0.086). Although it is difficult to arrive at a definite conclusion from a small dataset, our preliminary results suggest the potential role of DNA adducts in the colon carcinogenesis process. Additional studies with larger sample sizes are needed to confirm our preliminary finding. It is also important to identify the structural characterization of these unknown DNA adducts in order to have a better understanding of whether or not environmental carcinogens play a role in the aetiology of colon cancer.     

Mitochondrial DNA and Alzheimer’s disease: a first case–control study of the Tunisian population

Molecular Biology Reports - Alzheimer’s disease (AD) is the most common neurodegenerative disorder in humans and presents a major health problem throughout the world. The etiology of AD is...     

2q35-rs13387042 variant and the risk of breast cancer: a case–control study

Molecular Biology Reports - Breast Cancer is the most frequent neoplasm diagnosed among women worldwide. Genetic background and lifestyle/environment play a significant role in the disease...     

Chronic tinnitus and BDNF/GDNF CpG promoter methylations: a case–control study

Brain-derived neurotrophic factor (BDNF) and Glial-derived neurotrophic factor (GDNF) are neurotrophic factors that play key roles in the auditory pathway. While the relationship between serum levels and polymorphisms of BDNF/GDNF and chronic tinnitus is emphasized in the literature, there is no study showing the link between the promoter methylations of these genes and tinnitus. For this purpose, the relationship between chronic tinnitus and peripheral blood derived BDNF/GDNF promoter methylations was investigated to identify their role in the pathophysiology of tinnitus. In this case–control study, we examined the possible effects of BDNF/GDNF methylations in the blood samples of patients with tinnitus complaints for more than 3 months. Sixty tinnitus subjects between the ages of 18–55 and 50 healthy control subjects in the same age group who were free of any otorhinolaryngology and systemic disease were selected for examination. Methylation of total 12 CpG sites in BDNF and GDNF promoter regions were determined by the bisulfite-pyrosequencing method. Statistically significant differences were detected between BDNF CpG6 and GDNF CpG3-5-6 methylation ratios in the comparison of control group and the chronic tinnitus patients (P?=?0.002, 0.0005, 0.00003, and 0.0029, respectively). To our knowledge, this is the first study in the literature investigating the relationship between chronic tinnitus and peripheral blood derived BDNF/GDNF promoter methylations. It is believed that the current results might be supported by investigating the relationships between BDNF/GDNF methylations and genotypes in future research using higher sample sizes.

     

Replication of recently identified systemic lupus erythematosus genetic associations: a case–control study

Introduction

We aimed to replicate association of newly identified systemic lupus erythematosus (SLE) loci.

Methods

We selected the most associated SNP in 10 SLE loci. These 10 SNPs were analysed in 1,579 patients with SLE and 1,726 controls of European origin by single-base extension. Comparison of allele frequencies between cases and controls was done with the Mantel–Haenszel approach to account for heterogeneity between sample collections.

Results

A previously controversial association with a SNP in the TYK2 gene was replicated (odds ratio (OR) = 0.79, P = 2.5 × 10-⁵), as well as association with the X chromosome MECP2 gene (OR = 1.26, P = 0.00085 in women), which had only been reported in a single study, and association with four other loci, 1q25.1 (OR = 0.81, P = 0.0001), PXK (OR = 1.19, P = 0.0038), BANK1 (OR = 0.83, P = 0.006) and KIAA1542 (OR = 0.84, P = 0.001), which have been identified in a genome-wide association study, but not found in any other study. All these replications showed the same disease-associated allele as originally reported. No association was found with the LY9 SNP, which had been reported in a single study.

Conclusions

Our results confirm nine SLE loci. For six of them, TYK2, MECP2, 1q25.1, PXK, BANK1 and KIAA1542, this replication is important. The other three loci, ITGAM, STAT4 and C8orf13-BLK, were already clearly confirmed. Our results also suggest that MECP2 association has no influence in the sex bias of SLE, contrary to what has been proposed. In addition, none of the other associations seems important in this respect.     

Tapasin gene polymorphism in systemic onset juvenile rheumatoid arthritis: a family-based case–control study

Juvenile rheumatoid arthritis (JRA) comprises a group of chronic systemic inflammatory disorders that primarily affect joints and can cause long-term disability. JRA is likely to be a complex genetic trait, or a series of such traits, with both genetic and environmental factors contributing to the risk for developing the disease and to its progression. The HLA region on the short arm of chromosome 6 has been intensively evaluated for genetic contributors to JRA, and multiple associations, and more recently linkage, has been detected. Other genes involved in innate and acquired immunity also map to near the HLA cluster on 6p, and it is possible that variation within these genes also confers risk for developing JRA. We examined the TPSN gene, which encodes tapasin, an endoplasmic reticulum chaperone that is involved in antigen processing, to elucidate its involvement, if any, in JRA. We employed both a case–control approach and the transmission disequilibrium test, and found linkage and association between the TPSN allele (Arg260) and the systemic onset subtype of JRA. Two independent JRA cohorts were used, one recruited from the Rheumatology Clinic at Cincinnati Children's Hospital Medical Center (82 simplex families) and one collected by the British Paediatric Rheumatology Group in London, England (74 simplex families). The transmission disequilibrium test for these cohorts combined was statistically significant (χ² = 4.2, one degree of freedom; P = 0.04). Linkage disequilibrium testing between the HLA alleles that are known to be associated with systemic onset JRA did not reveal linkage disequilibrium with the Arg260 allele, either in the Cincinnati systemic onset JRA cohort or in 113 Caucasian healthy individuals. These results suggest that there is a weak association between systemic onset JRA and the TPSN polymorphism, possibly due to linkage disequilibrium with an as yet unknown susceptibility allele in the centromeric part of chromosome 6.     

Association of the UCP polymorphisms with susceptibility to obesity: case–control study and meta-analysis

This paper describes a case–control study and a meta-analysis performed to evaluate if the following polymorphisms are associated with presence of obesity: ?3826A/G (UCP1); ?866G/A, Ala55Val and Ins/Del (UCP2) and ?55C/T (UCP3). The case–control study enrolled 282 obese and 483 non-obese patients with type 2 diabetes. A literature search was made to identify all studies that evaluated associations between UCP1–3 polymorphisms and obesity. In the case–control study the distributions of the UCP variants did not differ between obese and non-obese groups (P > 0.05). Forty-seven studies were eligible for the meta-analysis and the results showed that the UCP2 ?866G/A and UCP3 ?55C/T polymorphisms were associated with protection to obesity in Europeans (OR = 0.89, 95 % CI 0.82–0.97 and OR = 0.88, 95 % CI 0.80–0.97, respectively). The UCP2 Ala55 val polymorphism was associated with obesity in Asians (OR = 1.61, 95 % CI 1.13–2.30). The UCP2 Ins/Del polymorphism was associated with obesity mainly in Europeans (OR = 1.19, 95 % CI 1.00–1.42). There was no significant association of the UCP1 ?3826A/G polymorphism with obesity. In our case–control study we were not able to demonstrate any association between UCP polymorphisms and obesity in T2DM patients; however, in the meta-analysis we detected a significant association of UCP2 ?866G/A, Ins/Del, Ala55Val and UCP3 ?55C/T polymorphisms with obesity.     

Rheumatoid arthritis–associated autoantibodies in non–rheumatoid arthritis patients with mucosal inflammation: a case–control study

IntroductionRheumatoid arthritis–associated autoantibodies (RA-AAB) can be present in serum years before clinical onset of rheumatoid arthritis (RA). It has been hypothesized that initiation of RA-AAB generation occurs at inflamed mucosal surfaces, such as in the oral cavity or lungs. The aim of this study was to assess systemic presence of RA-AAB in patients without RA who had oral or lung mucosal inflammation.MethodsThe presence of RA-AAB (immunoglobulin A [IgA] and IgG anti-cyclic citrullinated peptide 2 antibodies (anti-CCP2), IgM and IgA rheumatoid factor (RF), IgG anti-carbamylated protein antibodies and IgG and IgA anti-citrullinated peptide antibodies against fibrinogen, vimentin and enolase) were determined in sera of non-RA patients with periodontitis (PD, n = 114), bronchiectasis (BR, n = 80) or cystic fibrosis (CF, n = 41). Serum RA-AAB levels were compared with those of periodontally healthy controls (n = 36). Patients with established RA (n = 86) served as a reference group. Association of the diseases with RA-AAB seropositivity was assessed with a logistic regression model, adjusted for age, sex and smoking.ResultsLogistic regression analysis revealed that IgG anti-CCP seropositivity was associated with BR and RA, whereas the association with PD was borderline significant. IgA anti-CCP seropositivity was associated with CF and RA. IgM RF seropositivity was associated with RA, whereas the association with BR was borderline significant. IgA RF seropositivity was associated with CF and RA. Apart from an influence of smoking on IgA RF in patients with RA, there was no influence of age, sex or smoking on the association of RA-AAB seropositivity with the diseases. Anti-CarP levels were increased only in patients with RA. The same held for IgG reactivity against all investigated citrullinated peptides.ConclusionAlthough overall levels were low, RA-AAB seropositivity was associated with lung mucosal inflammation (BR and CF) and may be associated with oral mucosal inflammation (PD). To further determine whether mucosal inflammation functions as a site for induction of RA-AAB and precedes RA, longitudinal studies are necessary in which RA-AAB of specifically the IgA isotype should be assessed in inflamed mucosal tissues and/or in their inflammatory exudates.     

Thromboembolic risks of recombinant factor VIIa Use in warfarin-associated intracranial hemorrhage: a case–control study

Background

Recombinant factor VIIa (rFVIIa) may be used for rapid hemostasis in life-threatening hemorrhage. In warfarin-associated intracerebral hemorrhage (wICH), FVIIa use is controversial and may carry significant thromboembolic risks. We compared incidence of baseline thromboembolic risk factors and thromboembolism rates in wICH patients treated with additional rFVIIa to those treated with standard therapy of fresh frozen plasma (FFP) and vitamin K alone.

Methods

We identified 45 consecutive wICH patients treated with additional rFVIIa over 5-year period, and 34 consecutive wICH patients treated with standard therapy alone as comparison group. We compared the incidence of post-hemorrhage cardiac and extra-cardiac thromboembolic complications between two treatment groups, and used logistic regression to adjust for significant confounders such as baseline thromboembolic risk factors. We performed secondary analysis comparing the quantity of FFP transfused between two treatment cohorts.

Results

Both rFVIIa-treated and standard therapy-treated wICH patients had a high prevalence of pre-existing thromboembolic diseases including atrial fibrillation (73% vs 68%), deep venous thrombosis (DVT) or pulmonary embolism (PE) (22% vs 18%), coronary artery disease (CAD) (38% vs 32%), and abnormal electrocardiogram (EKG) (78% vs 85%). Troponin elevation following wICH was prevalent in both groups (47% vs 41%). Clinically significant myocardial infarction (MI), defined as troponin > 1.0 ng/dL, occurred in 13% of rFVIIa-treated and 6% of standard therapy-treated patients (p=0.52). Past history of CAD (p=0.0061) and baseline abnormal EKG (p=0.02) were independently associated with clinically significant MI following wICH while rFVIIa use was not. The incidences of DVT/PE (2% vs 9%; p=0.18) and ischemic stroke (2% vs 0%; p=0.38) were similar between two treatment groups. Recombinant FVIIa-treated patients had lower mean INR at 3 (p=0.0001) and 6 hours (p<0.0001) and received fewer units of FFP transfusion (3 vs 5; p=0.003).

Conclusions

Pre-existing thromboembolic risk factors as well as post-hemorrhage troponin elevation are prevalent in wICH patients. Clinically significant MI occurs in up to 13% of wICH patients. rFVIIa use was not associated with increased incidence of clinically significant MI or other venous or arterial thromboembolic events in this wICH cohort.

     

Health parameters in tail biters and bitten pigs in a case–control study

Health in relation to tail-biting behaviour was investigated on a problem farm. Quartets (n = 16) of age- and gender-matched fattening pigs including a tail biter (TB, n = 16), a victim (V, n = 16), a control in the same pen (C_tb, n = 10) and a control in a pen where no tail biting was observed (C_no, n = 14) were chosen by direct behavioural observation. Haematological and clinicochemical analyses, autopsy and histological examination of 16 different tissues were carried out. Tail lesion severity was evaluated both macroscopically, on the basis of inspection, and histologically, in the sagittally cut tail. Category effects were tested using Friedman's ANOVA by Ranks, Cochran's Q or a repeated-measure GLM and, if significant, pair-wise tests were conducted using Wilcoxon Signed Ranks or McNemar's Test. The number of received tail bites correlated better with histological than with macroscopic tail lesion scoring because of deep inflammation beneath healthy skin in some cases. Most individuals had mild inflammatory lesions in internal organs suggestive of generalized activation of the immune system, and 30% of the animals were anaemic, possibly because of systemic spread of infectious agents. V had more severe respiratory organ lesions and higher serum protein concentrations than all other categories of pigs. Liver- and muscle-specific enzymes (alanine aminotransferase, alkaline phosphatase and creatine kinase) differed between categories. In conclusion, most animals had signs of generalized activation of the immune system, possibly because of systemic spread of infectious agents. V pigs suffered from more severe inflammatory lesions than TB, C_tb or C_no. Deep infections may exist under healthy skin in the tail of bitten pigs.     

Metabolites predict cardiovascular disease events in persons living with HIV: a pilot case–control study

Introduction

Persons living with HIV (PLWH) are at higher risk for cardiovascular disease (CVD) events than uninfected persons. Current risk-stratification methods to define PLWH at highest risk for CVD events are lacking.

Methods

Using tandem flow injection mass spectrometry, we quantified plasma levels of 60 metabolites in 24 matched pairs of PLWH [1:1 with and without known coronary artery disease (CAD)]. Metabolite levels were reduced to interpretable factors using principal components analysis.

Results

Factors derived from short-chain dicarboxylacylcarnitines (SCDA) (p?=?0.08) and glutamine/valine (p?=?0.003) were elevated in CAD cases compared to controls.

Conclusion

SCDAs and glutamine/valine may be valuable markers of cardiovascular risk among persons living with HIV in the future, pending validation in larger cohorts.

     

Common polymorphisms of calpain-10 and the risk of polycystic ovary syndrome in Tunisian population: a case–control study

Recent studies have suggested that calpain-10 (CAPN10) gene polymorphisms play a role in the susceptibility to polycystic ovary syndrome (PCOS). The aim of the present study was to evaluate the possible association between three single nucleotide polymorphisms (SNPs) in CAPN10 gene: UCSNP-43 (rs3792267), UCSNP-19 (rs3842570), and UCSNP-63 (rs5030952) and PCOS in Tunisian cases and control women. Study subjects included 127 women with PCOS (mean age 29.8 ± 4.7 year) and 150 healthy women (mean age 33.5 ± 5.6 year). CAPN10 genotyping was carried-out by direct PCR and PCR–RFLP. Linkage disequilibrium pattern in the genomic region explored was determined by HAPLOVIEW 4.2 while reconstruction of haplotypes was done using PHASE 2.1. The phylogenetic distribution of haplotypes in the population was determined by ARLEQUIN 2.000. Six haplotypes were observed. None of SNPs associated with PCOS or its components while the haplotype H4 associated with the phenotype PCOS-obese (P < 0.025). Moreover the pair of haplotypes H1/H4 strongly associated with high blood-pressure (OR = 14.4, P < 0.012). This work confirms the association of CAPN10 gene with metabolic components in PCOS and highlights the role of haplotypes as strong and efficient genetic markers.     

ERCC1 haplotypes modify bladder cancer risk: A case–control study

Bladder cancer risk is highly influenced by environmental and/or predisposing genetic factors. In the last decades growing evidence of the major role played by DNA repair systems in the developing of bladder cancer has been provided. To better investigate the involvement of DNA repair genes previously reported to be significantly associated with bladder cancer risk, we examined in a case–control study (456 cases and 376 hospital controls) 36 single nucleotide polymorphisms (SNPs) in 10 DNA repair genes, through a better gene coverage and a deep investigation of the haplotype role. A single SNP analysis showed a significantly increased risk given by XRCC1-rs915927 G allele (OR = 1.55, CI 95% 1.02–2.37 for dominant model) and a protective effect of the rare alleles of 3 ERCC1 SNPs: rs967591 (OR = 0.66, CI 95% 0.46–0.95), rs735482 (OR = 0.62, CI 95% 0.42–0.90) and rs2336219 (OR = 0.63, CI 95% 0.43–0.93). Haplotype analysis revealed that cases had a statistically significant excess of XRCC3-TAGT and ERCC1-GAT haplotypes, whereas ERCC1-AAC, MGMT-TA, XRCC1-TGCC and ERCC2-TGAA haplotypes were significantly underrepresented. Together with other published data on large case–control studies, our findings provide epidemiological evidence supporting a link between DNA repair gene variants and bladder cancer development, and suggest that the effects of high-order interactions should be taken into account as modulating factors affecting bladder cancer risk. A detailed characterization of DNA repair genetic variation is warranted and might ultimately help to identify multiple susceptibility variants that could be responsible for joint effects on the risk.     

Improving emergency department performance by revising the patient–physician assignment process

Flexible Services and Manufacturing Journal - Emergency departments (EDs) are continuously exploring opportunities to improve their efficiency. A new opportunity lies in revising the...     

Livestock husbandry as a tool for carnivore conservation in Africa’s community rangelands: a case–control study

Conflict between people and wildlife is a major issue in both wildlife conservation and rural development. In African rangelands, species such as African wild dogs (Lycaon pictus), cheetahs (Acinonyx jubatus), lions (Panthera leo), leopards (Panthera pardus), and spotted hyaenas (Crocuta crocuta) may kill livestock and are therefore themselves killed by local pastoralists. Such conflict has led to the extirpation of these species from many areas, and also impacts the livelihoods of local livestock farmers. To investigate the possibilities for coexistence of people, livestock, and large predators in community rangelands, we measured the effectiveness of traditional livestock husbandry in reducing depredation by wild carnivores, using a case–control approach. Different measures were effective against different predator species but, overall, the risk of predator attack by day was lowest for small herds, accompanied by herd dogs as well as human herders, grazing in open habitat. By night, the risk of attack was lowest for herds held in enclosures (‘bomas’) with dense walls, pierced by few gates, where both men and domestic dogs were present. Unexpectedly, the presence of scarecrows increased the risks of attack on bomas. Our findings suggest that improvements to livestock husbandry can contribute to the conservation and recovery of large carnivores in community rangelands, although other measures such as prey conservation and control of domestic dog diseases are also likely to be necessary for some species.     

Maternal smoking during pregnancy and offspring attention-deficit/hyperactivity disorder: a case–control study in Japan

Although maternal smoking during pregnancy has been shown to be associated with an increased risk of offspring attention-deficit/hyperactivity disorder (ADHD) in Western countries, there is no empirical evidence in non-Caucasian. Purpose of the present study is to examine the relationship between maternal smoking during pregnancy and offspring ADHD in Japanese population. A case-control study design was adopted. A total of 90 pairs of children with ADHD and mothers as well as 270 corresponding control pairs were recruited throughout the study period. A psychiatrist interviewed all the mothers of children with ADHD and control children and elicited information regarding their lifestyles during pregnancy, including active and passive smoking or drinking habits, as well as psychosocial and perinatal factors. Diagnosis of ADHD was made by each physician in charge according to DSM-IV diagnostic criteria. Logistic regression analysis was used to calculate odds ratios (OR) and 95% confidence intervals (CI) with adjustments for other possible confounding factors. Maternal active smoking during pregnancy was associated with an approximately twofold increased risk of offspring ADHD, even after adjusting for socioeconomic and perinatal confounding factors (OR 1.8 95% CI 0.9-3.6). However, the association was obviously attenuated when factors regarding parental psychopathological vulnerability were controlled (OR 1.3 95% CI 0.6-2.9). On the other hand, maternal passive smoking during pregnancy failed to show any material association with ADHD. These results suggested that a significant part of the association between maternal smoking during pregnancy, and ADHD might be explained by genetic factors including parental psychopathological vulnerability.