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We have previously shown that sensitizations to several types of allergens distinguish subjects with and without adult-onset asthma in Finland. The aim was to analyze how age affects sensitization and asthma risk. We used previous population-based case-control data (N=456) from Finnish adult asthma patients with one or two matched controls. Asthma was diagnosed based on a typical history of asthmatic symptoms and lung function tests. Allergic sensitization was determined by skin prick test ( SPT) to 17 aeroallergens. Information on demographics was obtained by a questionnaire. Sensitization to more than one allergen type and the number of positive SPT reactions associated with younger age and asthma. Atopic subjects aged 65 and above were characterized by sensitization to only one to two allergens, with very few animal danders and without an association with asthma. Multiple sensitizations and animal dander sensitization are more common among Finnish asthmatic adults aged under 56 than among older asthmatics. Cohort studies are needed to understand timing of host-environmental interactions behind this. [ABSTRACT FROM AUTHOR]

Background There is a large global variation in the sensitization pattern and its association with allergic diseases. In temperate and tropical urban environments, mite monosensitization can be the predominant cause of allergic airway diseases, whereas in other environments, polysensitization is more typical. Sensitization to mite allergens associates with asthma. However, it is suggested that mite sensitization might play a minor role in Northern Europe. The aim of the study was to analyze how sensitization pattern affects the asthma risk in Finnish adults, with a special focus on mites. Methods A population-based case-control data ( N = 523) from Finnish adult asthma patients with one or two matched controls were used. Asthma was diagnosed based on a typical history of asthmatic symptoms and lung function tests. The allergic sensitization was determined based on skin prick test ( SPT) of five mites, three molds, and nine other aeroallergens. Information on demographics was obtained by a questionnaire. Results The proportion of sensitization to any allergen was 55% in the asthma group and 39% in the control group ( P = 0.001, OR 2.06, 95% CI = 1.35-3.14). Sensitization to animal dander, pollen, or Aspergillus fumigatus was associated with asthma. Polysensitization to more than one allergen types and the number of SPT-positive reactions associated with asthma, whereas sensitization to only one allergen type was not associated with asthma. Conclusions The large number of sensitizations to several types of allergens distinguishes subjects with asthma. Mite sensitization had little independent association with asthma in Finland. [ABSTRACT FROM AUTHOR]

FRAXE is a fragile site located at Xq27-8, which contains polymorphic triplet GCC repeats associated with a CpG island. Similar to FRAXA, expansion of the GCC repeats results in an abnormal methylation of the CpG island and is associated with a mild mental retardation syndrome (FRAXE-MR). We surveyed the GCC repeat alleles of FRAXE from 3 populations. A total of 665 X chromosomes including 416 from a New York Euro-American sample (259 normal and 157 with FRAXA mutations), 157 from a Chinese sample (144 normal and 13 FRAXA), and 92 from a Finnish sample (56 normal and 36 FRAXA) were analyzed by polymerase chain reaction. Twenty-seven alleles, ranging from 4 to 39 GCC repeats, were observed. The modal repeat number was 16 in the New York and Finnish samples and accounted for 24% of all the chromosomes tested (162/665). The modal repeat number in the Chinese sample was 18. A founder effect for FRAXA was suggested among the Finnish FRAXA samples in that 75% had the FRAXE 16 repeat allele versus only 30% of controls. Sequencing of the FRAXE region showed no imperfections within the GCC repeat region, such as those commonly seen in FRAXA. The smaller size and limited range of repeats and the lack of imperfections suggests the molecular mechanisms underlying FRAXE triplet mutations may be different from those underlying FRAXA.

The apparent associations between fragile X mutations and nearby microsatellites may reflect both founder effects and microsatellite instability. To gain further insight into their relative contributions, we typed a sample of 56 unrelated control and 37 fragile X chromosomes from an eastern Finnish population for FMR1 CGG repeat lengths, AGG interspersion patterns, DXS548, FRAXAC1, FRAXE and a new polymorphic locus, Alu-L. In the controls, the most common FMR1 allele was 30 repeats with a range of 20 to 47 and a calculated heterozygosity of 88%. A strong founder effect was observed for locus DXS548 with 95% of fragile X chromosomes having the 21 CA repeat (196 bp) allele compared to 17% of controls, while none of the fragile X but 69% of controls had the 20 repeat allele. Although the FRAXAC1 locus is much closer than DXS548 to FMR1 (7 kb vs. 150 kb), there was no significant difference between fragile X and control FRAXAC1 allele distributions. The FRAXE repeat, located 600 kb distal to FMR1, was found to show strong linkage disequilibrium as well. A newly defined polymorphism, Alu-L, located at approximately 40 kb distal to the FMR1 repeat, showed very low polymorphism in the Finnish samples. Analysis of the combined loci DXS548-FRAXAC1-FRAXE showed three founder haplotypes. Haplotype 21-19-16 was found on 27 (75%) of fragile X chromosomes but on none of controls. Three (8.4%) fragile X chromosomes had haplotypes 21-19-15, 21-19-20, and 21-19-25 differing from the common fragile X haplotype only in FRAXE. These could have arisen by recombination or from mutations of FRAXE. A second haplotype 21-18-17 was found in four (11.1%) fragile X chromosomes but only one (1.9%) control. This may represent a more recent founder mutation. A third haplotype 25-21-15, seen in two fragile X chromosomes (5.6%) and one (1.9%) control, was even less common and thus may represent an even more recent mutation or admixture of immigrant types. Analysis of the AGG interspersions within the FMR1 CGG repeat showed that 7/8 premutation chromosomes lacked an AGG whereas all controls had at least one AGG. This supports the hypothesis that the mutation of AGG to CGG leads to repeat instability and mutational expansion.