Association of Maternal Working Condition with Low Birth Weight: The Social Determinants of Health Approach.

BACKGROUND: The socioeconomic conditions have made more job opportunities available to women. This has created interest to conduct studies on the effect of working lifestyle on pregnancy outcomes. AIM: This study was conducted with the aim to assess the relationship between mothers' working status as a social determinant and the incidence of low birth weight (LBW) of the newborn. SUBJECTS AND METHODS: This case-control study was conducted on 500 women with normal weight infants (control group) and 250 women with LBW infants (case group) in selected hospitals in Tehran. Data were collected using a researcher-made questionnaire, designed to assess the effect of mothers' prenatal lifestyle, as a social determinant, on LBW of the newborn. A section of the questionnaire involved assessment of mother's working condition in terms of the work environment, activities, and job satisfaction. Data were analyzed using Chi-square and logistic regression tests. RESULTS: LBW among employed mothers was 5 times more likely than unemployed ones (odds ratio = 5.35, P < 0.001). Unfavorable work conditions such as humid environment, contact with detergents, and being in one standing or sitting position for long hours were significantly associated with LBW (P < 0.001). CONCLUSION: The present study showed that unfavorable work conditions were associated with LBW; therefore, they need special attention.

Exceptional human core promoter nucleotide compositions.

The proximal promoter sequences contain basic motifs for the expression of the downstream genes. We present genome-scale computational analyses of the 120-bp immediate upstream sequences to the +1 transcription start sites (TSSs) of 10,117 human protein-coding genes, and unravel exceptional genes in respect with the core promoter nucleotide composition. Our data reveal that while in 99% of the genes the absolute purine/pyrimidine ratio ranges between 0.2 and 2.5, certain genes show exceptional skew in this balance (e.g. ratios of 82.3 in VWA3A, 61.5 in Sox5, and 24.0 in BRWD3), and consist of islands of purines or pyrimidines. Furthermore, while over 95% of the genes lack more than one short tandem repeat (STR) in their core promoters, certain gene promoters are exceptionally rich in multiple STRs (e.g. eight consecutive STRs in UBE2QL1, and six STRs in GRIA2). We found sequence bias for the majority of those promoters across species, supporting functional roles for them in gene expression. Genes downstream to those promoters were also found to be of ontologic importance (i.e. we were able to track the majority of those genes to the lower species such as Saccharomyces cerevisiae and Caenorhabditis elegans). The exceptional promoters presented in this study lack the conventional motifs for the TATA, and TATA-less promoters, hence offering novel mechanisms for gene expression. They may also provide potential mechanisms for inter-individual variations in gene expression, and complex traits/disorders.

Novel mutations in the calreticulin gene core promoter and coding sequence in schizoaffective disorder.

We have recently reported the first case of mutation in the core promoter sequence of the human calreticulin gene in a family case of schizoaffective disorder. Remarkably, this gene coincides with a region of suggested linkage at 19p13.2, identified in a whole genome scan [Hamshere et al. (2005); Arch Gen Psychiatry 62;1081-1088]. The identified mutation was located at the conserved position -48 from the transcription start site, and was shown to be of functional effect, resulting in the aberrant expression of the gene. Following screening of the gene in 60 independent cases of schizoaffective disorder, we report novel germ-line mutations at positions -205 C > T and the conserved exon 5 (c: 682 C > T, pro228ser) in two unrelated cases of schizoaffective disorder. These mutations were disease-specific, and as for the -48 G > C mutation, neither was detected in a control population of 370 individuals, indicating a contribution of 3.17% in this sample series. To our knowledge, this is the first instance of disease-specific mutations in schizoaffective disorder, which warrants systematic screening of the regulatory and coding regions of the calreticulin gene in this disorder.

Skew in the human caveolin 1 gene upstream purine complex homozygote haplotype compartment in multiple sclerosis.

Caveolin 1 (CAV1) is a component of the myelin sheath and the expression of the gene encoding this protein is increased during myelination in Schwann cells and oligodendrocytes. We sought to investigate the homozygote haplotype compartment in a recently identified polymorphic purine complex at the upstream region of the human CAV1 gene in multiple sclerosis (MS). In a case/control study design, the region was characterized in 126 cases of MS diagnosed based on the Revised McDonald diagnostic criteria, and 460 controls. We report a skew in the homozygote haplotype compartment in the cases versus controls both in a qualitative and quantitative respect. Excess homozygosity for haplotypes was observed in the MS cases (corrected p<0.012, OR=2.54, CI 1.14-5.64). Furthermore, we observed eight homozygote haplotypes in the MS cases that were non-existent in the controls (p<0.0003, OR=20.27, CI 2.50-163.8). For the first time, our data highlight the CAV1 upstream purine complex as a novel susceptibility genomic locus in the pathophysiology of MS. Of utmost importance, the region has been conserved across species, including mouse, guinea pig, rhesus macaque, and human. The functional effect of this region remains to be clarified in the future studies.