Systematic review with meta-analysis: thiopurines decrease the risk of colorectal neoplasia in patients with inflammatory bowel disease.

BACKGROUND: Patients with inflammatory bowel disease (IBD) have a high risk of developing colorectal neoplasia. AIM: To investigate whether thiopurines can decrease the risk of developing colorectal neoplasia in patients with ulcerative colitis (UC) or Crohn's disease (CD). METHODS: We conducted a meta-analysis of 24 observational studies involving 76,999 participants to evaluate the risks of developing colorectal neoplasia in IBD patients receiving thiopurine treatment. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) for the risks of colorectal neoplasia were calculated using a random-effects model. RESULTS: The overall pooled estimate revealed a protective effect of thiopurine use on colorectal neoplasia in patients with IBD (OR = 0.63, 95% CI 0.46-0.86). The effect was significant in UC patients (OR = 0.67, 95% CI 0.45-0.98), but was not significant in CD patients (OR = 1.06, 95% CI 0.54-2.09). Thiopurines exposure significantly decreased the risk of colorectal cancer (CRC) (OR = 0.65, 95% CI 0.45-0.96) and advanced colorectal neoplasia (CRC and/or high-grade dysplasia) (OR = 0.62, 95% CI 0.44-0.89), but did not decrease the risk of dysplasia alone (OR = 0.90, 95% CI 0.37-2.21). Tendencies towards the protective effect of thiopurines were distinct in clinic-based studies (OR = 0.59, 95% CI 0.42-0.82) and case-control studies (OR = 0.40, 95% CI 0.26-0.62), but not in population-based studies (OR = 0.95, 95% CI 0.55-1.62) and cohort studies (OR = 0.98, 95% CI 0.81-1.18). Interestingly, studies conducted in Europe (OR = 0.48, 95% CI 0.31-0.77), rather than in North America (OR = 0.91, 95% CI 0.67-1.24), showed the protective effect of thiopurines. CONCLUSIONS: This meta-analysis revealed an antineoplastic effect of thiopurines on colorectal neoplasia in patients with IBD, particularly amongst patients with UC.

Screening and characterization of novel microsatellite loci in Lateolabrax japonicus.

Lateolabrax japonicus, an economically important species, is widely consumed in the offshore coasts of China, Korea, and Japan. We identified 10 new L. japonicus microsatellite markers, using a modified protocol of fast isolation by AFLP of sequences containing repeats. Thirty L. japonicus individuals were collected from Xiamen, China, to evaluate the degree of polymorphism. The number of identified alleles ranged from three to five. The polymorphism information content varied from 0.267 to 0.711, whereas the observed and expected heterozygosities ranged from 0.249 to 0.706 and 0.294 to 0.751, respectively. One of the 10 loci (L10) deviated from the Hardy-Weinberg equilibrium. These new microsatellite markers will provide a useful tool for the determination of population genetic structure and genetic diversity in L. japonicus.

Development of novel polymorphic microsatellite markers in Siganus fuscescens.

Rabbitfish, Siganus fuscescens, is widely distributed in the Indo-Pacific regions and eastern Mediterranean. Its dwelling place includes reef flats, coral reef regions, and seagrass meadows in tropical area and reef areas or shallow waters in locations at high latitudes. In the present study, 10 new polymorphic microsatellite markers were screened from 30 wild S. fuscescens individuals, using a method of fast isolation protocol and amplified fragment length polymorphism of sequences containing repeats. The number of polymorphic alleles per locus was 3 to 5 with a mean of 4.3, while the value of polymorphic information content ranged from 0.283 to 0.680. The values of the observed and expected heterozygosities were in the range 0.3333-0.8462 and 0.3011-0.7424, respectively. Deviation from Hardy-Weinberg equilibrium was not observed in this study. These polymorphic loci are expected to be effective in evaluating the genetic diversity, population structure, and gene flow and in determining the paternity in S. fuscescens, as well as for conservation management.

Isolation and characterization of microsatellite markers in Ruditapes philippinarum.

Ruditapes philippinarum is considered a commercially valuable species, which is commonly found in tidal flats along West Pacific coasts. In China, it is mainly distributed in the southeast sea. In this study, 16 novel microsatellite loci from the R. philippinarum genome were developed, using the protocol of fast isolation by amplified fragment length polymorphism of sequence containing repeats. Thirty-two wild-caught individuals were used to evaluate the degree of polymorphism of these markers. Our results show that there were 10 polymorphic loci and 6 monomorphic loci. The number of alleles per locus and the polymorphism information content ranged from 2 to 6 and from 0.199 to 0.751, respectively. The observed and expected heterozygosities varied from 0.1333 to 0.6207 and 0.1603 to 0.7412, respectively. Of all loci, only one locus was found to deviate significantly from Hardy-Weinberg equilibrium after Bonferroni correction. The loci identified here will provide useful information for future population genetic studies of R. philippinarum.

Isolation and characterization of eight novel microsatellite markers in Acanthopagrus schlegelii.

Acanthopagrus schlegelii is a warm temperate demersal fish, which inhabits the sediment substrate or rocky reefs in shallow seas. As this fish is a nutritionally endowed species with good palatability, it is a highly valuable commercial species for aquaculture and has a long historical standing in Western Pacific countries. Because the population of this fish is currently declining in China, studies and measures aimed at addressing this decline are needed. In this study, eight microsatellite markers were screened from 30 wild A. schlegelii fishes through the FIASCO method, whereby sequences containing repeats were obtained from amplified fragment length polymorphisms. The allelic number ranged from 3 to 5, with a mean number of 3.625. The average observed heterozygosity was 0.6290, ranging from 0.3214 to 0.8966, while the expected heterozygosity was 0.5435, ranging from 0.3452 to 0.6721. The value for polymorphism information content ranged from 0.313 to 0.666. These results show this population has moderate genetic variation and low genetic diversity. These novel polymorphic loci will be useful for future genetic studies of A. schlegelii.

Isolation and characterization of microsatellite markers in Atrina vexillum Born.

Atrina vexillum Born is an economically valuable species, widely distributed in the coastal waters of temperate and tropical areas of the Asia Pacific region. Twenty one novel microsatellite loci were identified in the genome of A. vexillum Born using the protocol for fast isolation by amplified fragment length polymorphism of sequence containing repeats. Thirty-two wild type individuals were used to evaluate the degree of polymorphism of these markers. We identified 13 polymorphic and 8 monomorphic loci with the number of alleles per locus and the polymorphism information content ranging from 2 to 5 and 0.141 to 0.664, respectively. The observed and expected heterozygosity varied from 0.1250 to 0.7000 and 0.1223 to 0.6216, respectively. Two loci deviated significantly from Hardy-Weinberg equilibrium (HWE) after Bonferroni correction, whereas the other loci were in HWE. These loci are expected to provide useful information for population genetic studies of A. vexillum Born.

Isolation and characterization of novel microsatellite markers in Mercenaria mercenaria.

Mercenaria mercenaria, also known as the hard clam, is widely distributed in the coastal waters of temperate and tropical areas in the Asian Pacific region. This species is widely popular in the international market, especially in the United States, Europe, and other Western countries, because of its high protein value, taste, and simple farming requirements. In this study, 17 novel microsatellite loci from the M. mercenaria genome were developed using the fast isolation by amplified fragment length polymorphism of sequences containing repeats protocol. Thirty-two wild individuals were used to evaluate the degree of polymorphism of these markers. Results indicated that there were 11 polymorphic loci and six monomorphic loci, and the number of alleles per locus and the polymorphism information content ranged from two to six and from 0.059 to 0.498, respectively. The observed and expected heterozygosity varied from 0.0625 to 0.5333 and 0.0615 to 0.4977, respectively. The Y1-4 locus deviated significantly from Hardy-Weinberg equilibrium (HWE) after Bonferroni correction was applied, while the other loci were in HWE. These loci will provide useful information for M. mercenaria population genetic studies.

Isolation and characterization of new microsatellite loci in Fenneropenaeus penicillatus.

Fenneropenaeus penicillatus is one of the major economic shrimp species in China. In this study, 14 novel microsatellite loci were developed using the fast isolation protocol with amplified fragment length polymorphism of sequences containing repeats (FIASCO). Polymorphisms were tested in 30 individuals from a single-wild population. The results showed that the number of alleles at each locus ranged from two to four, and the polymorphism information content varied from 0.314 to 0.692. The observed and expected heterozygosities ranged from 0.3343 to 0.6542 and from 0.3458 to 0.6657, respectively. Three loci deviated significantly from Hardy-Weinberg equilibrium after a Bonferroni correction was applied, while no deviations were detected in the other 11 loci. The new microsatellite loci identified in this study could be useful in future F. penicillatus population genetic, conservation research, population structure assessment, and linkage map construction studies.

Isolation and characterization of new microsatellite markers in red tail prawn, Fenneropenaeus penicillatus, an endangered species in China.

Until recently, Fenneropenaeus penicillatus was considered a commercial shrimp species. However, in 2005, it was included on the Red List as an endangered species by the Chinese government. In this study, 19 new microsatellite markers in F. penicillatus were developed and tested in samples of 32 wild individuals from Nanao, China. Twelve loci were polymorphic and 7 were monomorphic. Of the 12 polymorphic loci, the number of alleles per locus ranged from 3 to 6, with an average of 4.42 alleles per locus. The polymorphism information content ranged from 0.302 to 0.670, with a mean of 0.4817. The observed and expected heterozygosities ranged from 0.2250 to 0.8889 and from 0.1111 to 0.7750, respectively. Significant deviations from Hardy-Weinberg equilibrium (HWE, adjusted P < 0.0042) after a Bonferroni correction were observed in 3 loci (NA-9, NA-57, and NA-64), whereas the other 9 loci were in HWE. These new microsatellite markers will be useful in further research on the population genetic structure of F. penicillatus.

Isolation and characterization of microsatellite loci in hybrid giant tiger grouper.

The hybrid giant tiger grouper is a fish that has considerable commercial value and has become increasingly important for aquaculture in South East Asia since 2008. In order to prevent any reduction in genetic diversity in hybrid grouper as a result of aquaculture, we have identified 21 microsatellite markers that can be used to estimate genetic variation in the fish population. The number of alleles at polymorphic microsatellite loci ranged from 2 to 7, and observed and expected heterozygosities varied from 0.0323 to 0.9643 and 0.0921 to 0.7174, respectively. Polymorphism information content values ranged from 0.088 to 0.737. Nineteen of the 21 loci were in Hardy-Weinberg equilibrium (P > 0.005) after application of the Bonferroni correction (k = 10), the exceptions being ZZLD35 (P < 0.005) and ZZLD36 (P < 0.001). No linkage disequilibrium was detected. These 21 microsatellite markers are potentially of great value for analyzing genetic diversity to provide essential information for sustainable management of these fish.

Screening and characterization of novel polymorphic microsatellite markers from sea cucumber Holothuria leucospilota.

The sea cucumber Holothuria leucospilota has high me-dicinal value and rich nutritional edible value, and thus is a commercially important aquatic product in China. Microsatellite loci were developed and screened using a fast isolation protocol and amplified fragment length polymorphism of sequences containing repeats. In this study, 16 novel polymorphic microsatellite markers in H. leucospilota were identified, and the relevant genetic variability index was assessed using 30 individu-als from a wild population. The polymorphic information content ranged from 0.183 to 0.668, and the number of alleles per locus varied from 3 to 5. The observed and expected heterozygosities were 0.0370-0.5000 and 0.0776-0.6250, respectively. With the exception of 3 loci (Y1-15, Y11-1, and Y28), the polymorphic loci were in Hardy-Weinberg equilibrium (P > 0.003125). These polymorphic microsatellite loci will contribute to studies of genetic diversity, the research of population structure, and the design of conservation strategies for H. leucospilota.

Identification and characterization of rhizosphere fungal strain MF-91 antagonistic to rice blast and sheath blight pathogens.

AIM: To examine the inhibition effects of rhizosphere fungal strain MF-91 on the rice blast pathogen Magnaporthe grisea and sheath blight pathogen Rhizoctonia solani. METHODS AND RESULTS: Rhizosphere fungal strain MF-91 and its metabolites suppressed the in vitro mycelial growth of R. solani. The inhibitory effect of the metabolites was affected by incubation temperature, lighting time, initial pH and incubation time of rhizosphere fungal strain MF-91. The in vitro mycelial growth of M. grisea was insignificantly inhibited by rhizosphere fungal strain MF-91 and its metabolites. The metabolites of rhizosphere fungal strain MF-91 significantly inhibited the conidial germination and appressorium formation of M. grisea. Moreover, the metabolites reduced the disease index of rice sheath blight by 35·02% in a greenhouse and 57·81% in a field as well as reduced the disease index of rice blast by 66·07% in a field. Rhizosphere fungal strain MF-91 was identified as Chaetomium aureum based on the morphological observation, the analysis of 18S ribosomal DNA internal transcribed spacer sequence and its physiological characteristics, such as the optimal medium, temperature and initial pH for mycelial growth and sporulation production. CONCLUSIONS: Rhizosphere fungus C. aureum is effective in the biocontrolling of rice blast pathogen M. grisea and sheath blight pathogen R. solani both in in vitro and in vivo conditions. SIGNIFICANCE AND IMPACT OF THE STUDY: This study is the first to show that rhizosphere fungus C. aureum is a potential fungicide against rice blast and sheath blight pathogens.

First Report of Anthracnose of Digitaria sanguinalis Caused by Colletotrichum hanaui in China.

Hairy crabgrass (Digitaria sanguinalis (L.) Scop.) is a troublesome weed in most agricultural crops worldwide. Considerable efforts are made to limit the invasiveness and impact of crabgrass on crop productivity, including evaluation of fungi as biocontrol agents (3). In September 2005, a severe disease was observed on crabgrass plants in Zhejiang Province. Leaves and stems of the affected plant showed small, water-soaked, brownish spots that rapidly turned into longitudinal elliptic or spindle-shaped lesions, 6.5 to 8 × 22 to 24 mm, with a brown outer edge and a gray sunken central area. Coalescence of large lesions gave rise to extensive rotting and necrosis, and the stems were broken when the lesions encircled. Acervuli with brown setae and falcate single-celled spores, typical of some Colletotrichum species (2), formed on the lesions at this late stage. One fungal isolate (Col-68) was obtained from symptomatic tissues on potato dextrose agar that led to white-to-gray appressed mycelium growth with orange conidial masses at 28°C in darkness. Setae were septate, dark brown, rounded and sometimes lobed at base, 32.0 to 116.5 × 3.2 to 6.0 µm, with apices acute. Hyphae were septate, hyaline, 1.0 to 6.5 µm, and sometimes guttulate. Conidia were falcate or fusiform, apices acute or obtuse, and 8.16 to 26.37 × 2.9 to 9.2 µm with an average of 18.15 × 5.65 µm. Hyphopodial appressoria were smooth, globose to prolate, ovoid or obovoid with obtuse or cylindrical apices, edges entire, and 4.17 to 14.25 × 3.77 to 8.94 µm with an average of 7.0 × 6.9 µm. The pathogen was initially identified as a Colletotrichum species based on morphology. Suspensions of 3-day-old spores collected from potato dextrose liquid cultures (106 conidia per ml) were used to spray inoculate (15 ml per pot) three 9-cm-diameter pots of crabgrass seedlings at the three- to four-leaf growth stage. Another three pots of healthy crabgrass were simultaneously sprayed with sterilized distilled water without conidia, which served as noninoculated checks. The seedlings were kept at 25 to 28°C for 24 h under a polyethylene sheet cover in the greenhouse. Symptoms that developed in all inoculated seedlings were identical to those observed on the affected crabgrass in the field, meanwhile the seedlings inoculated with sterilized water had no significant symptoms, and the reisolated strain had the same characteristics as the original isolate. To diagnose the pathogen to the species level, three isolates were tested and an approximately 580-bp DNA amplicon of this isolate was amplified using the primers ITS1/ITS4. The sequence (GenBank Accession No. GQ456160) had 98% sequence identity with the sequences of Colletotrichum hanaui (GenBank Accession Nos. EU554101and EU554124), which is supported by phylogenetic analysis with bootstrap support. On the basis of the morphological, pathological characteristics, and phylogenetic tree, the isolated strain was identified as C. hanaui (1). To our knowledge, this is the first confirmed report of anthracnose of D. sanguinalis caused by newly described C. hanaui in China. References: (1) J. A. Crouch et al. Mycologia, 101:717, 2009. (2) B. C. Sutton. The Coelomycetes. CAB International Publishing, New York, 1980. (3) Y. Z. Zhu and S. Qiang. Chin. J. Biol. Control 20:206, 2004.

Effect of Schisandra chinensis extract and Ginkgo biloba extract on the pharmacokinetics of talinolol in healthy volunteers.

The authors investigated the effect of herbal medicine Schisandra chinensis extract (SchE) and Ginkgo biloba extract (GBE) on the oral pharmacokinetics of P-glycoprotein substrate talinolol in humans. Twelve healthy male volunteers took a single 100-mg oral dose of talinolol either alone or after pretreatment with 300 mg SchE twice daily or with 120 mg GBE three times daily for 14 days. On day 14, a single 100-mg oral dose of talinolol was administered. Plasma concentrations of talinolol from zero to 24 h were measured by high-performance liquid chromatography. SchE increased the area under the curve (AUC)(0-24) of talinolol by 47% (90% confidence interval (CI), 18-84%; p = 0.010), and GBE by 21% (90% CI = 11-32%; p = 0.002). The C(max) of talinolol increased by 51% (90% CI = 21-89%; p = 0.007) with SchE treatment and by 33% (90% CI = 18-51%; p = 0.002) with GBE treatment, respectively. The t(1/2) of talinolol increased by 7% (90% CI = -4% to 19%; p = 0.320) with SchE treatment and by 11% (90% CI = -12% to 38%; p = 0.436) with GBE treatment, respectively. The results suggest that both SchE and GBE significantly inhibited P-glycoprotein in humans. Patients receiving either SchE or GBE may require dose adjustments when treated with drugs primarily transported by P-glycoprotein.

Polymorphisms in ADAM33 are associated with allergic rhinitis due to Japanese cedar pollen.

BACKGROUND: A recent report provided evidence that a disintegrin and metalloprotease domain 33 (ADAM33), a member of the ADAM family, is a novel susceptibility gene in asthma linked to bronchial hyper-responsiveness. However, there has been no investigation of the genetic role of ADAM33 variants in nasal allergy. OBJECTIVE: The purpose of this study was to test the association between ADAM33 polymorphisms and Japanese cedar pollinosis (JCPsis), a most common seasonal allergic rhinitis in Japan. METHODS: We conducted a case-control association study among a Japanese population, involving 95 adult individuals with JCPsis and 95 normal healthy controls. A total of 22 single-nucleotide polymorphisms (SNPs) in ADAM33 were genotyped using PCR-based molecular methods. RESULTS: Six SNPs of ADAM33 gene, three in introns (7575G/A, 9073G/A and 12540C/T) and three in the coding region (10918G/C, 12433T/C and 12462C/T), were strongly associated with JCPsis (P = 0.0002-0.022 for absolute allele frequencies) and most of the SNPs were in linkage disequilibrium with each other. A higher frequency of the common alleles of these SNPs was noted for the subjects with JCPsis in comparison with healthy controls. We also identified a haplotype associated with the disease susceptibility. In addition, associations were found between ADAM33 polymorphisms and various cedar pollinosis phenotypes including clinical severity, eosinophil counts in nasal secretion and allergen-specific IgE levels in sera, but not total serum IgE levels. CONCLUSION: These results indicate that polymorphisms in the ADAM33 gene are associated with susceptibility to allergic rhinitis due to Japanese cedar pollen, but the functional relationship still needs clarification.

Association of the hCLCA1 gene with childhood and adult asthma.

Asthma is caused by bronchial inflammation. This inflammation involves mucus overproduction and hypersecretion. Recently, a mouse model of asthma showed that gob-5 is involved in the pathogenesis of asthma. The gob-5 gene is involved in mucus secretion and its expression is upregulated upon antigen attack in sensitized mice. The observation suggests that human homologue of gob-5, hCLCA1 (human calcium-dependent chloride channel-1), may be involved in human disease. We screened for single-nucleotide polymorphisms (SNPs) in hCLCA1 in the Japanese population. We identified eight SNPs, and performed association studies using 384 child patients with asthma, 480 adult patients with asthma, and 672 controls. In haplotype analysis, we found a different haplotype distribution pattern between controls and childhood asthma (P<0.0001) and between controls and adult asthma (P=0.0031). We identified a high-risk haplotype (CATCAAGT haplotype; P=0.0014) and a low-risk haplotype (TGCCAAGT haplotype; P=0.00010) in cases of childhood asthma. In diplotype analysis, patients who had the CATCAAGT haplotype showed a higher risk for childhood asthma than those who did not (P=0.0011). Individuals who had the TGCCAAGT haplotype showed a lower risk for childhood asthma than those who did not (P<0.0001). Our data suggested that variation of the hCLCA1 gene affects patients' susceptibility for asthma.

An asthma-associated genetic variant of STAT6 predicts low burden of ascaris worm infestation.

Th-2 immune mechanisms are involved in the pathology of asthma and in the protective immune response to parasitic worms. Common upregulating genetic variants of Th-2 immune signalling are risk factors for asthma, and we tested whether they may confer a counteradvantage in protecting against parasitic worms. We examined the intensity of infection by the parasitic worm, Ascaris lumbricoides, by microsopic counting of ascaris eggs in the stool of 614 schoolchildren from an area of endemic ascaris infection in China. We investigated the relationship between the intensity of ascaris infection and common, asthma-associated genetic variants of Th-2 and Th-1 immune signalling. Ascaris egg counts per gram of stool (epg), mean 1068 epg, ranged from barely detectable (<240 epg) to heavy (approximately 9600 epg) in a skewed distribution. Logistic regression, after exploratory discriminant analysis, showed a major association between a common genetic variant of the 3'-UTR regulatory elements of the signal transducer and transactivating factor (STAT6) (P=0.0002) and egg counts, at the 77 th centile. Linear regression after log transformation of egg counts confirmed a highly significant association with this STAT6 variant (P=0.001). Thus, a common, asthma-associated, genetic variant of the pivotal transduction and transactivating factor for Th-2 immune signalling, STAT6, predicts increased resistance to ascaris worm infection. The evolution of enhanced resistance to parasitic worm infection, through human genetic variation in Th-2 immune signalling, may represent one origin for asthma.

Genetic control of serum IgE levels: a study of low molecular weight protein tyrosine phosphatase.

Protein tyrosine phosphatases (PTPases) have recently been recognized as important modulators of various signal transduction pathways in immune cells. Genetic polymorphisms have been described in genes codifying for members of this family of enzymes, and the genetics of PTPases is predicted to play an important role in the etiology of immune diseases and of their clinical variability. The low molecular weight protein tyrosine phosphatase (ACP1 or LMPTP) is one of the few PTPases with a known genetic polymorphism, and has been proposed to be associated with atopic dermatitis in a small sample from an Italian population. In this paper we describe the association of the ACP1 polymorphism with total IgE levels in two independent samples from English and Italian populations. In both the samples the mean value of serum IgE is lower among subjects carrying the BC genotype than in other ACP1 genotypes. The BC genotype is associated with the highest total ACP1 enzymatic activity. Our data suggest that one or both of the ACP1 isoforms exert an inhibitory role on some signal transduction pathway relevant for IgE hyperproduction.

Low molecular weight PTP-IL-4RA interaction in atopy predisposition.

We recently described a protective effect of the low molecular weight protein tyrosine phosphatase (LMPTP) BC genotype, associated with the highest total enzymatic activity, against high serum IgE levels both in the English and the Italian populations. Here we test the hypothesis of a role of LMPTP in the negative modulation of IL-4 signal transduction checking for genetic interaction between interleukin-4 receptor alpha chain (IL-4RA) genetic polymorphisms and LMPTP polymorphism in the predisposition to high total IgE levels in the English population. We find a significant interaction between LMPTP polymorphism and the intracellular Gln/Arg polymorphism in position 551 of IL-4RA. Our data support the hypothesis of a direct or indirect biochemical interaction between LMPTP and IL-4RA resulting in different modulation of IL-4 signal transduction among joint genotypes.

IL-4 receptor alpha chain genetic polymorphism and total IgE levels in the English population: two-locus haplotypes are more informative than individual SNPs.

The IL-4RA locus encodes for the alpha chain of the IL-4 receptor, and is both a functional and positional candidate gene for atopy and allergic disease. Recently Ober et al. have shown that the study of haplotypes at multiple loci in the IL-4RA gene could be more informative than the separate study of single nucleotide polymorphisms (SNPs). One hundred and fifty subjects affected by atopic asthma and 150 healthy control subjects were studied in the English population (Oxford district). Subjects and controls were genotyped for the Ile50Val, Ser478Pro and Gln551Arg polymorphism of the IL-4 receptor alpha chain. The distribution of haplotypes 50-478 shows a highly significant association with IgE levels. In particular, the haplotype Val50/Pro478 is much less frequent in subjects with IgE levels > 100 U mL-1 than in those with IgE levels < 100 U mL-1. Furthermore, the distribution of haplotype 50-551 shows a weak association with IgE levels that is lacking for 478-551 haplotypes. A lower frequency of the Val50/Pro478 haplotype is also observed among asthmatic subjects as compared to healthy controls. With regard to individual SNPs (50 478 and 551), no significant association has been observed with IgE levels or with asthma, thus confirming the higher informative value of the haplotype analysis as compared to separate study on SNPs.