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Free fatty acids are the major source of fuel for mammals, and hormone sensitive lipase (LIPE) plays a critical role in lipid metabolism by mobilizing free fatty acids from stored triglycerides. We have identified and sequenced a partial cDNA for LIPE. Cosmids were identified by hybridization and mapped to 19q13.1-->q13.2 by FISH. Direct sequence analysis of a 1 kb segment of cosmid 26710 identifies a dinucleotide repeat in an intron upstream of exon 8 of human LIPE. This marker was heterozygous 82% of the time with 12 alleles (166-190 bp) detected in 122 chromosomes. The most likely order for this gene is: qter-[D19S178/LIPE]-(3 cM)-D19S47-(1 cM)-D19S190-RYR1-cen.

To obtain the regional localization of a dinucleotide repeat D19S120 (formerly designated LIPE) with 7 alleles and an observed heterozygosity of 73% (Levitt et al., 1992) we typed 40 CEPH families. Given the high heterozygosity and ease of typing, this marker represents a useful addition to the index map of chromosome 19.

We performed a double-blind, placebo-controlled, crossover study using 12 subjects to determine the effects of a single 50-mg dose of captopril on the response to nasal challenge with increasing doses of allergen. Levels of kinins, histamine and N-alpha-p-tosyl-L-arginine methyl ester (TAME)-esterase activity were measured in nasal lavages, and symptom scores and the number of sneezes were recorded. Captopril had no significant effects on histamine, TAME-esterase, sneezing or symptom scores. Peak postchallenge kinin levels, however, were significantly elevated (p less than 0.05) compared to placebo, while an increase in the magnitude of the dose-response curve was of marginal significance (p = 0.058). Thus, captopril causes increases in the kinin levels in nasal secretions during the allergic response. If increased kinin levels persist or worsen with chronic therapy, it is possible that they could exacerbate allergic symptoms during repeated seasonal exposure.

The six loci, beta-globin (HBBC), parathyroid hormone (PTH), oncogene c-Ha-ras-1 (HRAS1), insulin (INS), calcitonin (CAL) and catalase (CAT) loci, have been mapped to 11p in the order: CAT-CAL-PTH-HBBC-(HRAS1-INS). The purpose of the current study was to examine the linkage relationships, especially the multipoint relationships of these loci in detail. In the 18 families studied, a significant sex difference in recombination was found for the HBBC: HRAS1 linkage with more recombination in the male parent than the female parent (22 vs. 2%). The results of the multipoint analyses provided further evidence for the order CAT-CAL-PTH-HBBC-(HRAS1-INS); however, the order of the last two tightly linked loci is still not clear.

We quantitated puncture skin-test responses to 6 standardized, high-quality-inhalant allergen extracts in 320 adults - a stratified random sample, equally distributed between the sexes and among all decades between 20 and 60 years. For each subject, the 'average' IgE-mediated skin sensitivity to the entire panel of allergens (Allergy Index) was calculated. We evaluated correlations between log[total serum IgE]levels and Allergy Index versus quantitative measures of several environmental variables, including infection in childhood, residential history and smoking history. Age, sex and month bled were also included in these analyses. Although many significant intercorrelations were found among these variables, subsequent analyses by stepwise multiple regression showed that log[total IgE], age and smoking history were the best predictors of the Allergy Index and that the Allergy Index and sex were the best predictors of log[total IgE]. The negative relationship between smoking and skin-test responsiveness may reflect a tendency for allergic people to avoid the irritative effects of smoking on respiration. Our analyses, which simultaneously evaluated the effects of age, sex, Allergy Index and smoking history on log[total IgE]levels, did not support other studies which concluded that smoking significantly increases total serum IgE levels.

Relevant to the investigation of genetic factors involved in allergic response is the mode of inheritance of IgE levels, an important factor in allergic disease. Serum total IgE levels in 208 Pennsylvania Amish individuals from 23 nuclear families were studied. Males had a significantly higher mean in IgE level than females. There was also a significant negative relationship between age and IgE levels. Segregation analysis was used to fit a major gene model to the age- and sex-adjusted data. The environmental model was rejected (x2 = 41.12, p less than 0.005). The Mendelian codominant model was not rejected x2 = 8.84, p approximately or equal to 0.03) and gave a better fit to the data than the Mendelian dominant or recessive model.