Novel allele of the endothelial nitric oxide synthase gene polymorphism in Caucasian asthmatics.

The purpose of the present study was to investigate an association of the endothelial nitric oxide synthase (eNOS) gene polymorphism with asthma. eNOS intron4 variable number of tandem repeats (27 bp repeats) genotypes were determined in asthma patients and control subjects using microplate PCR. The Caucasian Asthma patients displayed three alleles while Caucasian controls displayed only two alleles. However, African Americans displayed all three alleles in both asthma patients and controls. African American controls displayed significantly higher a allele, significantly lower b allele, as well as c allele than those in Caucasians. This was the first report to show that there was a novel eNOS genotype present in asthmatic patients but not in control subjects in the Caucasian Community. The novel allele which we termed the c allele, could be a significant risk factor in the etiology of asthma in Caucasians. This novel allele could be involved in higher levels of NO in our Caucasian asthmatics.

Association of IL-13, RANTES, and leukotriene C4 synthase gene promoter polymorphisms with asthma and/or atopy in African Americans.

PURPOSE: IL-13, RANTES (Regulated on Activation, Normal T cells Expressed and Secreted), and cysteinyl leukotrienes are asthma and atopy mediators. Two RANTES -403(G to A) and -28(C to G), an -1055 IL-13(C to T), and a -444(A to C) leukotriene C4 synthase (LTC4S) single nucleotide polymorphisms (SNPs) have been shown in Caucasians and Asians as asthma and atopy risk factors. We studied these SNPs in African Americans with asthma and/or atopy. METHODS: We studied 61 patients with asthma and/or atopy and 129 to 157 newborn controls for the -403 RANTES, -28 RANTES, and -1055 IL-13 SNPs, as well as 47 patients and 60 newborn controls for the -444 LTC4S SNP. RESULTS: The two groups did not significantly differ at the genotypes of the -403 and -28 RANTES SNP. On the other hand, the mutant TT genotype for the -1055 IL-13 SNP was detected in 19.7% of patients versus 12.7% in controls (P < 0.04, OR 2.9, 95% CI 1.0-8.0), and the mutant T allele in 58.3% versus 36.6% in controls (P < 0.02, OR 2.4, 95% CI 1.1-5.2). In a similar fashion, for the -444 LTC4S SNP, the mutant AC genotype was detected in 19.1% versus 10.0% in controls (P > 0.28); mutant C allele had an OR of 2.1 (95% CI 0.7-6.3). CONCLUSION: African American asthmatics/atopics had higher frequency of the TT mutant gene for the -1055 IL-13 SNP and of its mutant T allele. Regarding the -444 LTC4S SNP, there was a definite difference, although not statistically significant, with an OR of 2.1 for the mutant AC genotype in patients. If these findings become reproduced by larger studies, it may suggest that IL-13 and LTC4S SNPs can be used as predictive markers for asthma/atopy in African Americans.

Immune defects in subjects with dysmorphic disorders.

Patients with dysmorphic disorders seem to have frequent respiratory infections that may be attributed to associated anatomic or neurological abnormalities, but immune defects may contribute to their susceptibility to infections. We screened subjects with dysmorphic conditions for major hematologic, B-cell and T-cell defects. We studied 84 subjects with dysmorphic disorders: 29 with chromosomal disorders, 27 with single gene disorders, and 28 with unclassified dysmorphic disorders. They were evaluated by physical examination; medical history suggestive of possible immune deficiency; complete blood count; serum immunoglobulin G (IgG), IgA, and IgM levels; and lymphocyte subsets. Low laboratory values (less than fifth percentile for age) were detected in 54.8%; was highest in the chromosomal disorder group (79.3%) followed by the single gene disorder group (55.6%) and was lowest in the unclassified dysmorphic disorder group (28.6%). The most common low values were in the CD19 and CD16/56 lymphocyte subpopulations followed by IgG and IgA levels. None of the subjects had neutropenia or thrombocytopenia. History of significant recurrent infections was noted in five subjects, all of whom had abnormal laboratory values. The highest frequency of abnormal laboratory values was in Down syndrome followed by Turner syndrome and chromosome deletions. We concluded that patients with dysmorphic disorders, particularly those with chromosomal disorders, have a high frequency of various B-cell and T-cell defects that may be contributing to their susceptibility to infection. Studies are needed to further delineate the immunologic defects in that population and to investigate a possible genetic basis at the molecular level.

Genes that permit or prevent infections.

In addition to heritable immunodeficiencies and polygenic susceptibility, acquisition genes and resistance genes are important genetic determinants of infectious diseases. Normal forms of acquisition genes permit entry of microorganisms into cells; mutations prevent entry. Normal forms of resistance genes prevent infections; mutations permit infections. The Genome Project has resulted in a growing list of each type. The current lists support important clinical principles. Many, if not most, pathogens readily enter cells unless prevented by antisepsis, blocking, and sterile techniques. Many, if not most, infections occur primarily in persons with heritable mutations of resistance genes.

Association of lung cancer death rates by parish with migration rate by age group.

Geographic distribution of cancer incidence, as judged from death certificates in Louisiana, shows evidence of strong epidemiological forces. Inspection of data on migration and lung cancer frequency shows them to be associated. Inmigrants account for a majority of the lung cancer deaths. Under assumptions of phenotypic complexity stemming from both genetic and environmental components, we used a multiple regression technique to test the significance of this association. Given the nature of the data and the assumptions of the analysis, there was a reasonable level of significance, suggesting that inmigration of older persons may be largely responsible for higher cancer rates in some parishes (counties) in Louisiana.