Maternal Genetic Variants of IL4/IL13 Pathway Genes on IgE With "Western or Eastern Environments/Lifestyles"

Purpose

We investigated maternal genetic effects of four IL-4/IL-13 pathway genes as well as their interactions with the "Western or Eastern lifestyles/environments" on IgE in Karelian children.

Methods

This study included 609 children and their mothers. Total IgE levels in children and mothers were measured and 10 single nucleotide polymorphisms (SNPs) in IL-4, IL-4Ra, IL-13, and STAT6 were genotyped in mothers and their children.

Results

The maternal G allele of IL-13 130 (rs20541) was significantly (P=0.001) associated with decreased IgE in children in the Karelian population (Pooling Finnish and Russian children), as well as in Finnish (P=0.030) and Russian children (P=0.018). The IgE levels were significantly (P=0.001) higher in Russian children whose mothers were homozygous for the G allele of the IL-4Ra 50 (rs1805010) SNP than that in Russian children of mothers who were AG heterozygotes or AA homozygotes. After accounting for children''s genotypes, we observed interactive effects on children''s IgE for maternal IL-13 130 genotypes (P=0.014) and maternal IL-4Ra 50 genotypes (P=0.0003) with "Western or Eastern" lifestyles/environments. With the adjustment for multiple comparisons using a false discovery rate (FDR) of 0.05, the interactive effect of the maternal IL-4Ra50 SNP was significant.

Conclusion

Maternal genetic variants in IL-4/IL-13 pathway genes, such as IL-13 130 and IL-4Ra50, influenced IgE levels in school children that were independent of the children''s genetic effects. These effects differ in "Western or Eastern" environments.     

Comorbid substance use reduces the health care contacts of suicide attempters with schizophrenia spectrum or mood disorders

Utilization of health care services has been found to differ between psychiatric disorders. However, the pattern of health care contacts among suicide attempters with mental disorders is not known. This study systematically investigated the pattern of health care contacts among suicide attempters with schizophrenia spectrum versus mood disorders with or without comorbid substance use disorders both before and after attempted suicide. All consecutive medically treated suicide attempters in Helsinki from January 15, 1997, to January 14, 1998, were identified (n = 1,198). Data were gathered on all their health care contacts within the 12 months before and after the index attempt. Whereas the clear majority of all suicide attempters with schizophrenia spectrum or mood disorders had a treatment contact during the 30 days following the attempt, half of those with pure substance use disorders were without any contact with health care. Comorbid substance use made treatment less likely after attempted suicide among both psychiatric disorder groups; those with schizophrenia spectrum and comorbid substance use disorders were seven times more often left without aftercare recommendation than those without substance use comorbidity. Comorbid substance use disorders among suicide attempters with schizophrenia spectrum disorders decrease the likelihood of active aftercare, despite high suicide risk.     

Fracture healing in paraplegic rats

In paraplegic rats, histomorphometric and chemical methods were used to evaluate callus production in tibial fractures stabilized by intramedullary nails. There were no differences in the mean sizes of fracture callus between paraplegic rats and their non-weight-bearing and weight-bearing controls. However, the variance of callus size was large in paraplegic rats. The concentration of nitrogen was high in calluses of paraplegic rats during the cartilaginous stage of healing. The hydroxyproline concentration did not differ between the groups. The rate of callus ossification was more rapid in paraplegic rats than in controls, but fracture calluses of paraplegic rats showed delayed accumulation of calcium and incomplete maturation of woven new bone. The results suggest that there are both mechanical and non-mechanical factors affecting callus formation in fractures below a spinal lesion.     

Labyrinthine malformation in the 22q11.2 deletion syndrome

Velocardiofacial syndrome and DiGeorge syndrome, integrating to form the 22q11.2 deletion syndrome, manifest frequently with hearing loss. Instead, a labyrinthine anomaly is only occasionally described in velocardiofacial syndrome/DiGeorge syndrome. We report a vestibular labyrinthine malformation demonstrated with computed tomographic scan in a patient with a palatal cleft and a 22q11.2 deletion presenting as velocardiofacial syndrome.     

Benzodiazepines and alcohol are associated with cases of fatal buprenorphine poisoning

Background  

Although buprenorphine therapy has proved to be successful in opioid maintenance treatments, the drug is also widely abused in many countries by intravenous injection or sniffing (“snorting”). In Finland, buprenorphine is the most important abused opioid causing fatal poisonings.     

Effect of occupational mercury exposure on plasma lysosomal hydrolases

Summary The activities of three plasma lysosomal hydrolases, -galactosidase, -glucuronidase and -N-acetylglucosaminidase, were studied in 20 workers exposed to metallic mercury vapor in a chlorine alkali plant and in 10 nonexposed referents. The urinary excretion and blood levels of mercury were determined on the day of study, and the history of mercury exposure was reviewed from the records of mercury concentrations in urine and blood over periods of up to 133 months. The average levels of -N-acetylglucosaminidase and -glucuronidase were higher in the plasma of exposed workers, but the difference was not significant. No significant positive correlation was seen between lyosomal enzyme activities and cumulative long-term exposure to mercury. It is concluded that measurement of plasma lysosomal hydrolase-activities is not of great value in the biological monitoring of workers exposed to low concentrations of metallic mercury vapor.In line with published data, the concentration of mercury showed a clearcut diurnal variation in nonexposed persons, persons currently exposed and persons with a history of past exposure. The excretion rate of mercury remained constant throughout the day.     

Interaction of alcohol and drugs in fatal poisonings

In Finnish data from 1995-2000, 1006 fatal poisonings due to alcohol (ethanol), a single drug or both were statistically analysed in retrospect to evaluate the interaction between alcohol and drugs. In 53% of these cases, low concentrations of some common benzodiazepines were present. The median postmortem blood alcohol concentration (BAC) was 3.3 percent per thousand (w/w) in the 615 alcohol poisonings, but significantly lower, ranging from 1.3 to 1.7 percent per thousand, when promazine, doxepin, amitriptyline or propoxyphene were found together with alcohol. When levomepromazine, temazepam or zopiclone were present, the median BAC was also significantly lower, 2.5-2.7 percent per thousand. Citalopram and diltiazem did not exhibit a significant effect. The median BAC was significantly lower in cases with high concentrations than in those with low concentrations of a drug (excluding citalopram), suggesting a positive concentration-effect relationship. Fatal toxicity indices (FTIs) were calculated by relating the number of deaths caused by a drug to the corresponding sales figures. Promazine had an extremely high FTI, followed by levomepromazine, propoxyphene, doxepin and amitriptyline. The other drugs had relatively low FTIs. The results reflect not only the acute toxicity of a given drug-alcohol combination but also the manners of use and abuse of these drugs.     

Non-participation and mortality in different socioeconomic groups: the FINRISK population surveys in 1972-92

BACKGROUND: Declining response rates pose a serious threat to the validity of estimates derived from epidemiological studies. If respondents and non-respondents differ systematically from each other, there can be a bias in the results of the study. A population-based cohort study was conducted to investigate disparities in socioeconomic structure between respondents and non-respondents and the contribution of these disparities to socioeconomic differences in total and cardiovascular mortality. DESIGN: Data comprised 32,354 male and female participants and 4890 non-participants aged 35-74 years who belonged to the sample in one of the five FINRISK surveys in 1972, 1977, 1982, 1987 or 1992 in Finland. They were followed up for 9 years and 6 months. RESULTS: It was found that the lower socioeconomic groups were over-represented among non-respondents both in men and women. When comparing the relative risk of death using the highest socioeconomic group of the participants as the reference group, it was found that although the socioeconomic gradient was similar for participants and non-participants-that is, lower groups had a higher risk of death-the risk was at a higher level among non-respondents. CONCLUSIONS: Basing analysis on participants does not distort the relative risk of death associated with socioeconomic position. However, it does underestimate the absolute risk.     

Detection and characterization of a novel functional polymorphism in the GSTT1 gene

A novel functional polymorphism in the GSTT1 gene associated with the non-conjugator phenotype has been identified. Sequencing of GSTT1 cDNA revealed a single nucleotide substitution, 310A>C, that altered the amino acid residue 104 from threonine to proline (T104P). Modelling studies of GSTT1 have suggested that residue 104 is located in the middle of alpha-helix 4. Introduction of an alpha-helix-disrupting proline most likely distorts the conformation of the protein. Individuals that lacked GSTT1 activity and carried the variant allele, tentatively denoted GSTT1*B, had no detectable GSTT1 immunoreactive protein. An allele-specific polymerase chain reaction method was developed to determine the frequency of the GSTT1*B allele. In 497 ethnic Swedes, the frequency of the active GSTT1*A allele was 0.65 [95% confidence interval (CI) 0.62-0.68] whereas the frequencies of the non-functional alleles GSTT1*O and the novel GSTT1*B allele were 0.34 (CI 0.31-0.37) and 0.01 (CI 0.01-0.02), respectively. In 100 Swedish Saamis, the GSTT1*B allele appeared to be slightly more common with a frequency of 0.03 (CI 0.01-0.07). The GSTT1 enzyme activity was measured in erythrocytes using methyl chloride as substrate. Individuals with the GSTT1*A/*A genotype had a two-fold higher GSTT1 activity compared to individuals with the GSTT1*A/*B genotype and subjects with the GSTT1*O/*B genotype totally lacked GSTT1 activity, indicating a strict gene-dose effect. By combining the analyses for the novel single nucleotide polymorphism with analyses for the deletion polymorphism, the accuracy in predicting all three GSTT1 conjugator phenotypes was improved from 96% to 99%.