Associated factors of behavioural problems in children at preschool age: the Hokkaido study on environment and children's health.

BACKGROUND: Finding associated factors with childhood behavioural problems as early as preschool age is important. Studies have revealed several factors including socioeconomic factors, which may vary among different cultural background and population. However, investigation in general Japanese population of preschool age has not been well demonstrated. Thus, the objective of this study was to examine associated factors of childhood behavioural problems using Strengths and Difficulties Questionnaire (SDQ) in a prospective birth cohort study. METHODS: Total 3813 SDQ were distributed between October 2014 and December 2015 to the subpopulation of prospective birth cohort study, the Hokkaido Study on Environment and Children's Health. The subpopulation consisted of participants who had reached age 5 and were born between April 2008 and December 2010. Baseline questionnaire filled at recruitment and birth record were used to obtain participant information. Children with total difficulties score ≧ 13 were defined as likelihood of behavioural problems. A total of 2553 children with valid answers were included into the analysis. The response rate was 67.1%. RESULTS: Number of children with likelihood of behavioural problems was 521 (20.4%). Boys showed more problematic scores than girls. Multivariate analysis found that maternal pre-pregnancy BMI ≧ 30 kg/m2 , primipara, maternal education lower than high school, family income during pregnancy < 3 million yen/year and boy gender were the factors associated with increased odds ratio of likelihood of child behavioural problems. CONCLUSIONS: This study found that prenatal socioeconomic factors were associated with likelihood of child behavioural problems at preschool age in Japan.

Phosphorus flame retardants in indoor dust and their relation to asthma and allergies of inhabitants.

Organophosphate esters are used as additives in flame retardants and plasticizers, and they are ubiquitous in the indoor environment. Phosphorus flame retardants (PFRs) are present in residential dust, but few epidemiological studies have assessed their impact on human health. We measured the levels of 11 PFRs in indoor floor dust and multi-surface dust in 182 single-family dwellings in Japan. We evaluated their correlations with asthma and allergies of the inhabitants. Tris(2-butoxyethyl) phosphate was detected in all samples (median value: 580 µg/g in floor dust, 111 µg/g in multi-surface dust). Tris(2-chloro-iso-propyl) phosphate (TCIPP) was detected at 8.69 µg/g in floor dust and 25.8 µg/g in multi-surface dust. After adjustment for potential confounders, significant associations were found between the prevalence of atopic dermatitis and the presence of TCIPP and tris(1,3-dichloro-2-propyl) phosphate in floor dust [per log10 -unit, odds ratio (OR): 2.43 and 1.84, respectively]. Tributyl phosphate was significantly associated with the prevalence of asthma (OR: 2.85 in floor dust, 5.34 in multi-surface dust) and allergic rhinitis (OR: 2.55 in multi-surface dust). PFR levels in Japan were high compared with values reported previously for Europe, Asia-Pacific, and the USA. Higher levels of PFRs in house dust were related to the inhabitants' health status.

Influence of leukotriene pathway polymorphisms on clinical responses to montelukast in Japanese patients with asthma.

WHAT IS KNOWN AND OBJECTIVE: Montelukast, a cysteinyl leukotriene receptor 1 antagonist, is safe and efficacious in patients with asthma. The mechanisms underlying the significant interpatient variability in response to montelukast are not clear but are believed to be, in part, because of genetic variability. METHODS: To examine the associations between polymorphisms in candidate genes in the leukotriene pathway and outcomes in patients with asthma on montelukast for 4-8 weeks, we evaluated the changes in peak expiratory flow (PEF), forced expiratory volume in 1 s (FEV(1·0) ) and patients' subjective symptom before and after montelukast treatment. DNA was collected from 252 Japanese participants. RESULTS AND DISCUSSION: Two single-nucleotide polymorphisms (SNPs) in the ALOX5 (rs2115819) and LTA4H (rs2660845) genes were successfully typed. There was no difference between members of the general population (n = 200) and patients (n = 52) in each genotype frequency. Significant associations were found between SNP genotypes in the LTA4H gene and changes in PEF and FEV(1·0) . The PEF and FEV(1·0) responses to montelukast in the A/A genotypes (n = 4) for the LTA4H SNP were significantly higher than those in the G allele carriers (A/G+G/G) (n = 17). WHAT IS NEW AND CONCLUSION: Despite the small sample size, our results suggest that genetic variation in leukotriene pathway candidate genes contributes to variability in clinical responses to montelukast in Japanese patients with asthma.

Maternal folate, alcohol and energy metabolism-related gene polymorphisms and the risk of recurrent pregnancy loss.

Epidemiological studies have suggested that the condition of recurrent pregnancy loss (RPL) may be multifactorial, with both genetic predisposition and environmental factors potentially involved in its pathogenesis. The aim of this study is to elucidate the associations between maternal folate, alcohol and energy metabolism-related gene polymorphisms and the risk of RPL. This case-control study, which involved 116 cases with two or more instances of RPL and 306 fertile controls, was performed in the city of Sapporo, Japan. The associations between eight single nucleotide polymorphisms of folate, alcohol and energy metabolism-related genes [methylenetetrahydrofolate reductase (MTHFR), 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR), 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR), alcohol dehydrogenase 1B (ADH1B), aldehyde dehydrogenase 2 (ALDH2), beta-3-adrenergic receptor (ADRB3) and peroxisome proliferator-activated receptor gamma (PPARG)], and RPL were assessed. Without consideration of cigarette smoking or alcohol use, the risk of RPL significantly decreased in women with the MTHFR rs1801133 TT, MTR rs1805087 AG or ALDH2 rs671 AA genotype (P < 0.05). The risk of RPL associated with cigarette smoking and alcohol use decreased significantly in women carrying the MTHFR rs1801133 T allele [odds ratio (OR), 0.51; 95% confidence interval (CI), 0.27-0.95]. Similarly, the risk of RPL significantly decreased in women carrying the MTR rs1805087 G allele (OR, 0.44; 95% CI, 0.23-0.85). Our findings suggest that maternal gene polymorphisms related to folate metabolism may decrease the risk of RPL. Molecular epidemiological studies are needed to unequivocally elucidate the multifactorial effects of both genetic and environmental factors on human fecundity.

Associations between hazard indices of di-n-butylphthalate and di-2-ethylhexylphthalate exposure and serum reproductive hormone levels among occupationally exposed and unexposed Chinese men.

The knowledge on the dose-response relationships between cumulative phthalate exposure and reproductive hormones in human are lacking. To assess the characteristics of the associations between hazard index (HI) of cumulative di-n-butylphthalate (DBP) and di-2-ethylhexylphthalate (DEHP) exposures and serum concentrations of free testosterone (fT), estradiol, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), we used restricted cubic spline function to characterize the dose-response curves between the HI values and reproductive hormones for 74 male workers occupationally exposed to high levels of DBP and DEHP, and 63 male construction workers as comparison group matched for age and smoking status. The median of HI value was 5.30 for exposed workers, 53.0-fold that of unexposed workers (0.10). 89.2% of exposed workers and 1.6% of unexposed workers have HI over 1.00. We observed a borderline significantly negative association between HI and fT in exposed workers (r=-0.195, p=0.096), but not in unexposed workers. The exposed workers showed inverted long-tailed J-shaped fT and FSH curves, and small changes in the LH curve, whereas unexposed workers had inverted and flattened-S-shaped fT and mirror-S-shaped LH and FSH curves. Both T production and hypothalamo-pituitary-testis (HPT) axis function were damaged in workers with high HI of phthalate exposures. HPT feedback function was activated in workers with both high and low HI, and plays an important role in preventing fT level from further decreasing with a rise in HI.

Relationships between mite allergen levels, mold concentrations, and sick building syndrome symptoms in newly built dwellings in Japan.

UNLABELLED: This study investigated the possible relationships between exposures to mite allergen and airborne fungi with sick building syndrome (SBS) symptoms for residents living in newly built dwellings. We randomly sampled 5709 newly built dwellings in six prefectures from northern to southern Japan. A total of 1479 residents in 425 households participated in the study by completing questionnaire surveys and agreeing to environmental monitoring for mite allergen (Der 1), airborne fungi, aldehydes, and volatile organic compounds. Stepwise logistic regression analyses adjusted for confounders were used to obtain odds ratios (OR) of mite allergen and fungi for SBS symptoms. Der 1 had a significantly high OR for nose symptoms. Rhodotorula had a significantly high OR for any symptoms, and Aspergillus had significantly high OR for eye symptoms. However, the total colony-forming units had a significantly low OR for throat and respiratory symptoms. Eurotium had a significantly low OR for skin symptoms. In conclusion, dust-mite allergen levels and indoor airborne Rhodotorula and Aspergillus concentrations may result in SBS symptoms in newly built dwellings. PRACTICAL IMPLICATIONS: Various factors can cause sick building syndrome symptoms. This study focused on biologic factors such as dust-mite allergen and airborne fungi in newly built dwellings in Japan. Dust-mite allergen levels were significantly associated with higher rates of nose symptoms, airborne Rhodotorula concentrations were significantly associated with higher rates of any symptoms, and Aspergillus concentrations were significantly associated with higher rates of eye symptoms. Measures should be taken to reduce mite allergen levels and fungal concentrations in these dwellings.

A novel microsatellite polymorphism of sodium channel beta1-subunit gene (SCN1B) may underlie abnormal cardiac excitation manifested by coved-type ST-elevation compatible with Brugada syndrome in Japanese.

OBJECTIVE: Brugada syndrome (BrS) is a rare sodium channelopathy typically seen in middle-aged, Southeast Asian males conferring high risks of cardiac sudden death. Loss-of-function mutations in SCN5A encoding the alpha-subunit of cardiac sodium channels may account partially for its etiology. We aimed to study whether mutations in the beta-subunits of sodium channel (SCN1B and SCN2B) would also be associated with abnormal cardiac excitation in BrS. METHODS: 85 Japanese patients suspected to have BrS undertook a diagnostic challenge test with a sodium channel blocker, pilsicainide. Genetic screenings were performed for SCN5A, SCN1B and SCN2B by PCR-SSCP and direct sequence of amplicons in the patients and 50 healthy controls. RESULTS: 30 patients exhibited BrS-like ECG pattern (i.e., a coved-type ST-segment elevation) either at baseline or after the drug challenge. Genetic screenings revealed a sequence variation (p.R190Q) and 3 polymorphisms (p.H558R, p.R1193Q, IVS24+53T > C) in SCN5A, a sequence variation (g.-26G > T) and 2 polymorphisms (IVS1+53G > T and IVS3 +2996(TTA)8-15) in SCN1B and 2 polymorphisms (IVS2+27A > G, IVS2+76G > A) in SCN2B. A logistic analysis revealed that male, middle age (40 - 59 years of age) and IVS3+2996(TTA)8 of SCN1B were significantly (p < 0.05) associated with the development of BrS-like ECG pattern with odds ratios (95% confidence intervals) of 5.9 (1.8 - 19.6), 2.9 (1.4 - 6.1) and 2.3 (1.1 - 4.9), respectively. While the IVS3+2996(TTA)8 allele has not been reported in Caucasians previously, its allelic frequency in the patients exhibiting the BrS-like ECG pattern (0.250) was comparable to that in the healthy controls (0.260). CONCLUSION: The IVS3+ 2996(TTA)8 allele commonly seen in Japanese would not be pathogenic itself but may render male, middle-aged Japanese more susceptible to BrS.

Association between indoor exposure to semi-volatile organic compounds and building-related symptoms among the occupants of residential dwellings.

UNLABELLED: The aim of this study was to evaluate the levels of semi-volatile compounds (SVOCs) in residential detached houses in Sapporo, Japan, and whether exposure to these SVOCs was associated with the development of building-related symptoms named 'sick house syndrome' (SHS). The definition of SHS is fundamentally the same as that of the sick building syndrome (SBS). The presence of symptoms of SHS was evaluated using a validated self-administered questionnaire. Surveys and samplings of air and house dust in 41 dwellings were performed from October 2006 to January 2007, and 134 occupants responded to questionnaires. Samples were analyzed to quantify the concentrations of eight plasticizers, eleven phosphate triester flame retardants, two alkyl phenols used as anti-oxidants, and one organochlorine synergist called s-421, by gas chromatography-mass spectrometry and gas chromatography-flame photometry. The compounds frequently detected were di-n-butylphthalate, di(2-ethylhexyl)phthalate (DEHP), and dibutylhydroxytoluene in air, and DEHP and tris(2-butoxyethyl)phosphate (TBEP) in dust. Tributylphosphate was strongly and directly associated with mucosal symptoms of SHS; s-421 was also directly associated with mucosal symptoms of SHS. On the contrary, some chemicals such as diethylphthalate and TBEP were inversely associated with SHS. In future studies, we plan to assess these associations in a larger population. PRACTICAL IMPLICATIONS: This study suggests that it may be possible to reduce building-related symptoms by altering exposure to certain SVOCs, such as tributylphosphate commonly found in ceiling and wall coverings and s-421 used as a synergist for pyrethroids. The association between SHS and s-421 suggested that use of pyrethroid insecticides could elicit symptoms of SHS. However, further studies are necessary to test the associations observed in the present study and to examine whether the SVOCs associated with symptoms are causative agents or simply surrogates for some other factor that is causing the symptoms.

Diffusive sampling and measurement of microbial volatile organic compounds in indoor air.

Microbial volatile organic compounds (MVOC), chemicals emitted from various microorganisms, in indoor air have been of concern in recent years. For large field studies, diffusive samplers are widely used to measure indoor environments. Since the sampling rate of a sampler is a fundamental parameter to calculate concentration, the sampling rates of eight MVOC with diffusive samplers were determined experimentally using a newly developed water-bubbling method: air was supplied to the MVOC-solutions and the vapor collected in an exposure bag, where diffusive and active samplers were placed in parallel for comparison. Correlations between the diffusive and active samplings gave good linear regressions. The sampling rates were 30-35 ml/min and the detection limits were 0.044-0.178 microg/m(3), as determined by GC/MS analysis. Application of the sampling rates in indoor air was validated by parallel sampling of the diffusive and active sampling method. 5% Propan-2-ol/CS(2) was the best solvent to desorb the compounds from absorbents. The procedure was applied to a field study in 41 dwellings. The most frequently detected compounds were hexan-2-one and heptan-2-one, with 97.5% detection rates and geometric mean values of 0.470 and 0.302 microg/m(3), respectively. This study shows that diffusive samplers are applicable to measure indoor MVOC levels. Practical Implications At present, there are still limited reports on indoor Microbial Volatile Organic Compounds (MVOC) levels in general dwellings and occupants' health. Compared with active sampling methods, air sampling using a diffusive sampler is particularly advantageous for use in large field studies due to its smallness, light-size, easy-handling, and cost-effectiveness. In this study, sampling rates of selected MVOC of the diffusive sampler were determined using the water-bubbling method: generating gases by water-bubbling and exposing the diffusive and active samplers at the same time. The obtained sampling rates were validated, and the method was applied to the field study.

Regional differences in residential environments and the association of dwellings and residential factors with the sick house syndrome: a nationwide cross-sectional questionnaire study in Japan.

UNLABELLED: This study was conducted to clarify regional differences in residential factors and the association of those factors with dwellings having sick house syndrome (SHS) problems. The survey was conducted in six areas of northern and southern Japan. In terms of regional differences, dampness was not as severe in the dwellings in Sapporo as compared with that in areas in the south. SHS was defined using five categories of nasal, throat and respiratory, skin and general symptoms, which appeared frequently or not frequently and improved upon leaving the home. The dampness index was estimated by the sum of the presence of several indicators: condensation on the window panes and/or wall, visible mold growth, moldy odor, slow-drying wet towels in the bathroom, and water leakage. The dwellings where inhabitants showed any symptoms of SHS comprised 3.7% of all surveyed dwellings. We found significant associations between SHS and dampness index, odors, and stuffiness of the air. For dampness, the adjusted odds ratio (OR) increased with increased dampness index, adjusting for the age of the house, pets indoors, stuffiness of the air, and odors. These results showed an increased risk when several dampness indicators appeared simultaneously. PRACTICAL IMPLICATIONS: To evaluate the associations of residential environments and Sick House Syndrome (SHS), this cross-sectional questionnaire study was conducted on 2297 dwellings in six areas in Japan from 2003 to 2004. The dwellings where inhabitants showed any of nasal, throat and respiratory, skin and general symptoms comprised 3.7% of all surveyed dwellings, and an increased risk for SHS was found when several dampness indicators, 'condensation', 'visible mold growth', 'moldy odor', 'slow drying wet towels in the bathroom' and 'water leakage', appeared simultaneously.

Proinflammatory cytokine polymorphisms and the risk of preterm birth and low birthweight in a Japanese population.

Pregnancy and parturition involve a complex and poorly understood molecular and biological interplay between mother and fetus. Inflammatory cytokines have been reported to be associated with fetal growth and parturition. The aim of this study was to examine whether common proinflammatory cytokine polymorphisms are associated with preterm birth (PTB), low birthweight or intrauterine growth restriction in a Japanese population. We assessed a consecutive series of 414 women who had singleton deliveries in Sapporo, Japan between 2001 and 2005. Genotyping of IL1A -889C/T, +4845G/T (A114S), IL1B -511C/T, -31C/T, IL2 -384T/G and IL6 -634C/G polymorphisms was determined by an allelic discrimination assay. The risk of PTB significantly increased in women carrying the IL1A -889T allele (CC genotype [reference]; CT genotype, odds ratios (OR): 2.5; 95% confidence intervals (95% CI): 1.4-4.8; CT+TT genotypes [dominant genotype model], OR: 2.5, 95% CI: 1.3-4.6). Similarly, the risk of PTB significantly increased in women carrying the IL1A +4845T allele (GG genotype [reference]; GT genotype, OR: 2.4, 95% CI: 1.3-4.4; GT+TT genotypes [dominant genotype model], OR: 2.3, 95% CI: 1.2-4.2). The frequency of the IL1A TT haplotype in mothers with PTB was significantly higher than in mothers who had a term birth (P < 0.001), whereas the frequency of the IL1A CG haplotype in mothers who had a PTB was significantly lower (P < 0.001). Our findings suggest that the polymorphisms and haplotypes in the IL1A gene are associated with PTB in Japanese women.

Maternal smoking during pregnancy and genetic polymorphisms in the Ah receptor, CYP1A1 and GSTM1 affect infant birth size in Japanese subjects.

Genetic susceptibility to tobacco smoke might have relation to adverse pregnancy outcomes. To estimate the effects of maternal smoking and genetic polymorphisms on infant birth weight and length, we conducted a prospective cohort study of 293 women who delivered singleton live births in Sapporo, Japan. Birth weight and length were significantly lower among infants born to continuously smoking women having the aryl hydrocarbon receptor (AhR) wild type genotype (Arg/Arg; 211 g +/- 76 g; 1.2 cm +/- 0.4 cm, p < 0.01 and p < 0.01, respectively), the CYP1A1 variant genotype (m1/m2 + m2/m2; 170 g +/- 64 g, 0.8 cm +/- 0.3 cm, p < 0.01 and p < 0.05, respectively), or the GSTM1 null genotype (171 g +/- 58 g, 0.6 cm +/- 0.3 cm, p < 0.01 and p < 0.05, respectively). When combinations of these genotypes were considered, birth weight and length were significantly lower for infants of continuously smoking women in the AhR wild type + CYP1A1 variant group (315 g +/- 116 g; 1.7 cm +/- 0.6 cm, p < 0.01 and p < 0.01, respectively) and in the CYP1A1 variant + GSTM1 null group (237 g +/- 92 g; 1.3 cm +/- 0.5 cm, p < 0.05 and p < 0.01, respectively). These genotypes did not confer adverse effects among women who had never smoked; therefore, maternal smoking in combination with maternal AhR, CYP1A1 and GSTM1 genetic polymorphisms may adversely affect infant birth size.

Relationships of C-reactive protein, uric acid, and glomerular filtration rate to arterial stiffness in Japanese subjects.

The relationships between C-reactive protein (CRP), uric acid (UA), glomerular filtration rate (GFR), and arterial stiffness have not been fully investigated. The aim of this study was to clarify whether CRP, UA, and estimated GFR are related to arterial stiffness estimated using brachial-ankle pulse wave velocity (baPWV). The subjects were local government employees (3412 men and 854 women). baPWV, CRP, UA, GFR, and conventional risk factors were evaluated. Multiple linear regression analyses revealed that CRP and UA were significantly related to an elevation of PWV in male and female subjects, and that the estimated GFR was significantly related to an elevation of PWV in male subjects. Significant progressive increases in baPWV were observed across the quartiles of CRP in male subjects and for UA in male and female subjects. In female subjects, the relationship of quartile CRP to baPWV had marginal significance (P = 0.055). But, in male and female subjects, quartile of estimated GFR had no significant association with PWV. These results suggest that CRP and UA are associated with an increase of arterial stiffness in male and female subjects, and that estimated GFR is possibly related to arterial stiffness in male subjects.

Effect of the blockade of mu1-opioid and 5HT2A-serotonergic/alpha1-noradrenergic receptors on sweet-substance-induced analgesia.

RATIONALE: Sweet-substance-induced analgesia has been widely studied, and the investigation of the neurotransmitters involved in this antinociceptive process is an important way for understanding the involvement of the neural system controlling this kind of antinociception. OBJECTIVE: The aim of this study was to investigate the involvement of opioid and monoaminergic systems in sweet-substance-induced analgesia. METHODS: The present work was carried out in an animal model with the aim of investigating whether acute (24 h) or chronic (14 days) intake of a sweet substance, such as sucrose (250 g/l), is followed by antinociception. Tail withdrawal latencies in the tail-flick test were measured before and immediately after this treatment. Immediately after the recording of baseline values, independent groups of rats were submitted to sucrose or tap-water intake and, after chronic treatment, they were pretreated with intraperitoneal administration of (1) naltrexone at 0.5, 1, 2 or 3 mg/kg; (2) naloxonazine at 5, 10, 20 or 30 mg/kg; (3) methysergide at 0.5, 1, 2 or 3 mg/kg; (4) ketanserin at 0.5, 1, 2 or 3 mg/kg; or (5) physiological saline. RESULTS: Naltrexone and methysergide at two major doses decreased sweet-substance-induced analgesia after chronic intake of a sweet substance. These effects were corroborated by peripheral administration of naloxonazine and ketanserin. CONCLUSIONS: These data give further evidence for: (a) the involvement of endogenous opioids and a mu1-opioid receptor in the sweet-substance-induced antinociception; (b) the involvement of monoamines and 5HT2A serotonergic/alpha1-noradrenergic receptors in the central regulation of the sweet-substance-produced analgesia.

Maternal genetic polymorphisms in CYP1A1, GSTM1 and GSTT1 and the risk of hypospadias.

Hypospadias is one of the most common congenital anomalies. Increased exposure to environmental factors (endocrine-disrupting chemicals and smoking) or maternal endogenous estrogen may cause hypospadias because male sexual differentiation is dependent on normal androgen homeostasis. Moreover, interactions between genetic factors and cigarette smoking and other chemicals have been suggested. It has been demonstrated that the CYP1A1 metabolizes not only environmental chemicals but also estrogens, and glutathione-S-transferases (GSTs) are detoxification enzymes that protect cells from toxicants by conjugation with glutathione. In this study, to investigate the association of CYP1A1 (MspI), GSTM1 and GSTT1 polymorphisms with hypospadias, a case-control study of 31 case mothers who had boys with hypospadias and 64 control mothers was performed in Japan. These polymorphisms were investigated by PCR-based methods using DNA from peripheral lymphocytes. We found that the heterozygous CYP1A1 and heterozygous and homozygous CYP1A1 were less frequent in the case mothers than in the control mothers [adjusted odds ratio (OR)=0.17, 95% confidence interval (CI)=0.04-0.74, OR = 0.28, 95% CI = 0.08-0.97, respectively]. We found no effect of maternal smoking on the hypospadias risks among the gene polymorphisms. The results suggest that mothers with the CYP1A1 MspI variant allele may have a decreased risk for hypospadias.

Symptoms in relation to chemicals and dampness in newly built dwellings.

OBJECTIVES: As the airtightness of dwellings has recently increased, problems associated with indoor air pollution and dampness have become important environmental health issues. The aim of this study was to clarify whether symptoms in residents living in newly built dwellings were related to chemicals and dampness. METHODS: Symptoms of 317 residents were surveyed by standardized questionnaires, and the concentrations of formaldehyde, acetaldehyde, and 17 volatile organic compounds (VOCs) in their homes were measured. Dampness (condensation on window panes and/or walls, and mold growth) was identified by questionnaires given to the householders or their partners. RESULTS: Some VOCs (toluene, butyl acetate, ethylbenzene, alpha-pinene, p-dichlorobenzene, nonanal, and xylene) were significantly related to the symptoms, and the sum of all VOCs (all identified VOCs) was significantly related to throat and respiratory symptoms [odds ratio (OR) for eye symptoms =2.4; 95% confidence interval (CI) 1.0-5.5], although the concentrations of VOCs were relatively low. As for the dampness index, condensation on window panes and/or walls was related to all symptoms, and mold growth was related to all symptoms except skin, throat and respiratory and general symptoms. As the number of dampness signs increased, the ORs increased for the symptoms except general symptoms (OR for nose symptoms = 4.4, 95% CI 1.6-11.9). CONCLUSION: Both VOCs and dampness were significantly related to symptoms. We should take measures to reduce the concentrations of VOCs, dampness and microbial growth in dwellings.

Ah receptor, CYP1A1, CYP1A2 and CYP1B1 gene polymorphisms are not involved in the risk of recurrent pregnancy loss.

The etiology of recurrent pregnancy loss (RPL) remains unclear, but it may be related to a possible genetic predisposition together with involvement of environmental factors. We examined the relation between RPL and polymorphisms in four genes, human aryl hydrocarbon (Ah) receptor, cytochrome P450 (CYP) 1A1, CYP1A2 and CYP1B1, which are involved in the metabolism of a wide range of environmental toxins and carcinogens. All cases and controls were women resident in Sapporo, Japan and the surrounding area. The Ah receptor, CYP1A1, CYP1A2 and CYP1B1 genotypes were assessed in 113 Japanese women with recurrent pregnancy loss (RPL) and 203 ethnically matched women experiencing at least one live birth and no spontaneous abortion (control). No significant differences in Ah receptor, CYP1A1, CYP1A2 and CYP1B1 genotype frequencies were found between the women with RPL and the controls [Ah receptor: Arg/Arg (reference); Arg/Lys and Lys/Lys, odds ratio (OR)=0.67; 95% confidence interval (CI)=0.40-1.11, CYP1A1: m1m1 (reference); m1m2 and m2m2, OR = 0.86; 95% CI = 0.53-1.40, CYP1A2: C/C and C/A (reference); A/A, OR = 1.16; 95% CI = 0.71-1.88, CYP1B1: Leu/Leu (reference); Leu/Val and Val/Val, OR = 1.18; 95% CI = 0.68-2.02]. The present study suggests that the Ah receptor, CYP1A1, CYP1A2 and CYP1B1 gene polymorphisms are not major genetic regulators in RPL.