Association of MHC region SNPs with irritant susceptibility in healthcare workers.

Irritant contact dermatitis is the most common work-related skin disease, especially affecting workers in "wet-work" occupations. This study was conducted to investigate the association between single nucleotide polymorphisms (SNPs) within the major histocompatibility complex (MHC) and skin irritant response in a group of healthcare workers. 585 volunteer healthcare workers were genotyped for MHC SNPs and patch tested with three different irritants: sodium lauryl sulfate (SLS), sodium hydroxide (NaOH) and benzalkonium chloride (BKC).

Genetic Basis of Irritant Susceptibility in Health Care Workers.

Objective: The aim of this study was to investigate the association of single nucleotide polymorphisms (SNPs) within genes involved in inflammation, skin barrier integrity, signaling/pattern recognition, and antioxidant defense with irritant susceptibility in a group of health care workers.

Methods: The 536 volunteer subjects were genotyped for selected SNPs and patch tested with three model irritants: sodium lauryl sulfate (SLS), sodium hydroxide (NaOH), and benzalkonium chloride (BKC). Genotyping was performed on genomic DNA using Illumina Goldengate custom panels.

Genetic variants in the major histocompatibility complex class I and class II genes are associated with diisocyanate-induced Asthma.

Objective: To investigate the association between single nucleotide polymorphisms (SNPs) located across the major histocompatibility complex and susceptibility to diisocyanate-induced asthma (DA).

Methods: The study population consisted of 140 diisocyanate-exposed workers. Genotyping was performed using the Illumina GoldenGate major histocompatibility complex panels.

Genetic variants within the MHC region are associated with immune responsiveness to childhood vaccinations.

The influence of genetic variability within the major histocompatibility complex (MHC) region on variations in immune responses to childhood vaccination was investigated. The study group consisted of 135 healthy infants who had been immunized with hepatitis B (HBV), 7-valent pneumococcal conjugate (PCV7), and diphtheria, tetanus, acellular pertussis (DTaP) vaccines according to standard childhood immunization schedules. Genotype analysis was performed on genomic DNA using Illumina Goldengate MHC panels (Mapping and Exon Centric).

Association between IL-1A single nucleotide polymorphisms and chronic beryllium disease and beryllium sensitization.

Objective: To determine if single nucleotide polymorphisms (SNPs) in interleukin (IL) IL-1A, IL-1B, IL-1RN, IL-2, IL-9, and IL-9R were associated with chronic beryllium disease (CBD) and beryllium sensitization (BeS).

Methods: Forty SNPs in six IL genes were evaluated in 85 individuals with CBD, 61 individuals with BeS, and 730 individuals without BeS or CBD (nonsensitized) using a 5' nuclease polymerase chain reaction assay. Logistic regression was used to evaluate the association between IL SNPs, CBD, and BeS, adjusting for plant-site and HLA-DPB1Glu69 in additive, dominant, and recessive inheritance models.

Impact of negatively charged patches on the surface of MHC class II antigen-presenting proteins on risk of chronic beryllium disease.

Chronic beryllium disease (CBD) is a granulomatous lung disease that occurs primarily in workers who are exposed to beryllium dust or fumes. Although exposure to beryllium is a necessary factor in the pathobiology of CBD, alleles that code for a glutamic acid residue at the 69th position of the HLA-DPbeta1 gene have previously been found to be associated with CBD. To date, 43 HLA-DPbeta1 alleles that code for glutamic acid 69 (E69) have been described.

TNF-alpha polymorphisms in chronic beryllium disease and beryllium sensitization.

Objective: Tumor necrosis factor-alpha (TNF-alpha) is a potent cytokine involved in normal immune functions. The aim of this study was to investigate if there is an association between chronic beryllium disease or beryllium sensitization and two variants of the TNF-alpha gene located at -308 and -238 called TNF-alpha-308*02 and TNF-alpha-238*02.

Methods: TNF-alpha-308 and TNF-alpha-238 genotyping was conducted in a large, population-based cohort consisting of 886 beryllium workers (92 individuals with chronic beryllium disease, 64 who were beryllium sensitized, and 730 individuals without sensitization or disease).

DNA-sequence determination of exon 2 of a novel HLA-DPB1 allele, HLA-DPB1*0403.

Sequence determination using HLA-DPB1 allele-specific primers for a DNA sample donated by an African-American individual revealed the presence of a novel haplotype. This new allele was found as a heterozygote together with HLA-DPB1*0402. The new allele was similar to HLA-DPB1*1601, however, it varied in two single nucleotide polymorphisms resulting in alanine residues at positions 55 and 56 of the mature protein rather than aspartic acid and glutamic acid, respectively.

Induction of CYP1A1 and CYP1B1 and formation of carcinogen-DNA adducts in normal human mammary epithelial cells treated with benzo[a]pyrene.

Inter-individual variation in formation of carcinogen-DNA adducts and induction of cytochrome P450 genes was measured in 23 cultured normal human mammary epithelial cell (NHMEC) strains established from reduction mammoplasty tissue. Semi-confluent cells were exposed to 4 microM benzo[a]pyrene (BP) for 12 h and BP-DNA adduct levels were measured by chemiluminescence immunoassay using antiserum elicited against DNA modified with r7, t8-dihydroxy-t-9, 10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE). BP-DNA adduct levels for 22 of 23 different cell strains ranged from non-detectable (three samples) to about 15 adducts/10(8) nucleotides.

Waf-1 (p21) and p53 polymorphisms in breast cancer.

p53 is a transcription factor for Waf-1/p21, a cyclin-dependent kinase inhibitor. Certain polymorphic variants of Waf-1 and p53 have been evaluated for their association with cancer risk. Previous studies indicated that certain p53 polymorphisms confer an increased risk of breast cancer [odds ratios (ORs) and 95% confidence intervals (CIs) = 2.