Role of Toll-like Receptor 3 Variants in Aspirin-Exacerbated Respiratory Disease

Purpose

Although the mechanism of virus-induced, aspirin-exacerbated respiratory disease (AERD) is not known fully, direct activation of viral components through Toll-like receptor 3 (TLR3) has been suggested. TLR3 recognizes double-stranded RNA (dsRNA), and activates nuclear factor-κB and increases interferon-γ, which signals other cells to induce airway inflammation in asthma. Considering the association of TLR3 in viral infections and AERD, we investigated whether promoter and non-synonymous variants of TLR3 were associated with AERD.

Methods

The three study groups, 203 with AERD, 254 with aspirin-tolerant asthma (ATA), and 274 normal healthy controls (NC) were recruited from Ajou University Hospital, Korea. Two polymorphisms, -299698G>T and 293391G>A [Leu412Phe], were genotyped using primer extension methods.

Results

Genetic associations were examined between two genetic polymorphisms of TLR3 (-299698G>T and 293391G>A [Leu412Phe]) in the three study groups. AERD patients that carried the GG genotype of 293391G>A showed a significantly lower frequency compared with ATA in both co-dominant (P=0.025) and dominant models (P=0.036). Similarly, in the minor allele frequency, the A allele was significantly higher (P=0.023) in AERD compared with ATA for this polymorphism. AERD patients who carried HT2 [GA] showed a significantly higher frequency than other haplotypes in co-dominant (P=0.02) and recessive (P=0.026) models.

Conclusions

Our findings suggest that the -299698G>T and 293391G>A [Leu412Phe] polymorphisms of the TLR3 gene are associated with the AERD phenotype.     

Association between CDH13 Variants and Cardiometabolic and Vascular Phenotypes in a Korean Population

Purpose

Although some CDH13 single nucleotide polymorphisms (SNPs) have been shown to be determinants of blood adiponectin levels, the clinical implications of CDH13 variants are not yet completely understood. The purpose of this study was to evaluate the effects of SNPs of CDH13 on metabolic and vascular phenotypes.

Materials and Methods

We included 238 hypertensive subjects and 260 age- and sex-matched controls. Seven tagging-SNPs were identified in the CDH13 gene by whole gene sequencing. The association between these SNP variants and the risk of hypertension, metabolic traits, and carotid intima-media thickness (IMT) was examined.

Results

Minor allele carriers of rs12444338 had a lower risk of hypertension, but the association turned out just marginal after adjusting confoudners. Blood glucose levels were higher in the minor allele carriers of c.1407C>T (p=0.01), whereas low-density lipoprotein-cholesterol levels were greater in those of rs6565105 (p=0.02). The minor allele of rs1048612 was associated with a higher body mass index (p=0.01). In addition, the mean carotid IMT was significantly associated with rs12444338 (p=0.02) and rs1048612 (p=0.02).

Conclusion

These results provide evidence that CDH13 variants are associated with metabolic traits and carotid atherosclerosis in Koreans. This study shows the multifaceted effects of CDH13 variants on cardiometabolic risk.     

The ADA*2 allele of the adenosine deaminase gene (20q13.11) and recurrent spontaneous abortions: an age-dependent association

OBJECTIVE:

Adenosine deaminase acts on adenosine and deoxyadenosine metabolism and modulates the immune response. The adenosine deaminase G22A polymorphism (20q.11.33) influences the level of adenosine deaminase enzyme expression, which seems to play a key role in maintaining pregnancy. The adenosine deaminase 2 phenotype has been associated with a protective effect against recurrent spontaneous abortions in European Caucasian women. The aim of this study was to investigate whether the G22A polymorphism of the adenosine deaminase gene is associated with recurrent spontaneous abortions in Brazilian women.

METHODS:

A total of 311 women were recruited to form two groups: G1, with a history of recurrent spontaneous abortions (N = 129), and G2, without a history of abortions (N = 182). Genomic DNA was extracted from peripheral blood with a commercial kit and PCR-RFLP analysis was used to identify the G22A genetic polymorphism. Fisher''s exact test and odds ratio values were used to compare the proportions of adenosine deaminase genotypes and alleles between women with and without a history of recurrent spontaneous abortion (p<0.05). The differences between mean values for categorical data were calculated using unpaired t tests. The Hardy-Weinberg equilibrium was assessed with a chi-square test.

RESULTS:

Statistically significant differences were identified for the frequencies of adenosine deaminase genotypes and alleles between the G1 and G2 groups when adjusted for maternal age.

CONCLUSIONS:

The results suggest that the adenosine deaminase *2 allele is associated with a low risk for recurrent spontaneous abortions, but this association is dependent on older age.     

Probable role of Beta 2-adrenergic receptor gene haplotype in toluene diisocyanate-induced asthma

Purpose

A genetic polymorphism of the beta 2-adrenergic receptor is a major factor associated with the asthmatic phenotype. The association of this polymorphism with toluene diisocyanate (TDI)-induced asthma has not been investigated. We examined 103 TDI-induced asthma patients (TDI-OA), 60 asymptomatic exposed controls (AEC), and 263 unexposed healthy controls (NC) in order to identify beta 2-adrenergic receptor gene (ADRB2) polymorphisms and the possible association with TDI-induced asthma.

Methods

Single nucleotide polymorphisms (SNPs) of ADRB2 were genotyped by direct sequencing. Serum-specific IgE and IgG levels were measured using an enzyme-linked immunosorbent assay. Phenotypes and clinical patient parameters were compared.

Results

SNPs were identified (-47 T>C, -20 T>C, Arg16Gly A>G, Gln27Glu C>G, Leu134Leu G>A, Arg175Arg C>A) during ADRB2 screening (from -231 to 793 bp). No significant differences in allelic and genotypic frequencies were noted for any of the six ADRB2 SNPs. The Arg16Gly A>G, Leu134Leu G>A, and Arg175Arg C>A SNPs and haplotype 1 [TTACGC] were significantly associated with specific IgE antibodies to the TDI-human serum albumin (HSA) conjugate in TDI-exposed subjects (P<0.05). Exposed workers with the ADRB2 ht1/ht1 homozygote had a significantly higher TDI-HSA conjugate-specific IgE sensitization rate than did those with the null ht1 haplotype (odds ratio, 15.40; 95% confidence interval, 1.81-131.06).

Conclusions

ADRB2 polymorphisms may affect IgE-specific sensitization to TDI-HSA conjugate in TDI-exposed workers.     

Effects of heme precursors on CYP1A2 and POR expression in the baculovirus/Spodoptera frugiperda system

Objective

CYP1A2 and NADPH-CYP450 oxidoreductase (POR) were expressed in the baculovirus/Spodoptera frugiperda (sf9) system. The aim of this study was to investigate the effects of heme precursors on the expression of CYP1A2 and POR.

Methods

The heme precursors [δ-Aminolaevulinic Acid (5-ALA), Fe³⁺ and hemin] were introduced into the system to evaluate their effects on the expression of CYP1A2, POR and their co-expression. All the proteins were identified using immunoblotting, CO-difference spectroscopy, or cytochrome c assay.

Results

In the present study, functional CYP1A2 and POR were successfully expressed in the baculovirus/sf9 system, and both of them showed high activities. Co-addition of 5-ALA and Fe³⁺ significantly improved expression of CYP1A2 by about 50% compared with the addition of 5-ALA, Fe³⁺ or hemin alone. Either co-addition of 5-ALA and Fe³⁺ or addition of 5-ALA or Fe³⁺ alone improved the POR expression level 2 fold and its activity 7-10 fold compared with control (no addition). However, unlike CYP1A2, there was no difference between the co-addition and addition of these heme precursors alone. Different ratios of BvCYP1A2 to BvPOR also affected the co-expression of CYP1A2 and POR, with a 3:1 ratio of BvCYP1A2 / BvPOR significantly increasing their co-expression. Surprisingly, the addition of 0.1 mM 5-ALA or Fe³⁺ alone, but not their co-addition, could significantly improve the CYP1A2 and POR co-expression (P < 0.05).

Conclusion

5-ALA and Fe³⁺ increased the expression of CYP1A2 and POR in a baculovirus/sf9 system, but the pattern of their expression was different between their expression alone and co-expression.     

Association of the adiponectin gene variations with risk of ischemic stroke in a Korean population

Purpose

Stroke is the second leading cause of death and a major cause of morbidity and mortality worldwide. Evidence of variations in adiponectin(AdipoQ) genes that are associated with ischemic stroke has not been consistent, and it is unclear whether the same loci contribute to these associations in the Korean population. Using a Korean population, we tested ischemic stroke-associated AdipoQ markers.

Materials and Methods

In a preliminary genome-wide association study using 320 250 k Affymetrix NSP chips, AdipoQ was found to be associated with ischemic stroke in Koreans. To study of AdipoQ, a further 673 ischemic stroke patients and 267 unrelated individuals without a history of stroke or transient ischemic attack were examined in a case-control study.

Results

Six polymorphisms (rs182052G > A, rs16861205G > A, rs822391T > C, rs822396A > G, rs12495941G > T and rs3774261A > G) that had a minor allele frequency of over 1% were strongly associated with stroke (p < 0.05). Two of these, rs822391T > C and rs822396A > G showed this association on both dominant and additive logistic regression analysis after adjusting for age and sex. The haplotypes ht 1 (AGGCGG and AAGTAG) were significantly associated with susceptibility to stroke.

Conclusion

Our findings show that polymorphisms in AdipoQ are associated with risk for ischemic stroke in the Korean population. This study lends further support to the putative role of AdipoQ in stroke.     

Association of β₂-adrenergic receptor polymorphism with work-related symptoms in workers exposed to wheat flour

Purpose

Our previous study indicated that the presence of wheat-specific IgG1 and IgG4 antibodies was associated with work-related symptoms in workers exposed to wheat flour. We performed this study to investigate the genetic polymorphisms of β₂-adrenergic receptors and wheat-specific antibodies in association with the clinical parameters of baker''s asthma.

Materials and Methods

In total, 379 subjects working in a single industrial bakery were enrolled in this study. The skin prick test was performed with common inhalant allergens and wheat flour extract. The presence of serum- specific IgE, IgG1, and IgG4 antibodies to wheat flour were determined by ELISA. Whole blood samples were obtained for genotype analysis. Subjects were genotyped with regard to five candidate single nucleotide polymorphisms (SNPs) of the β₂-adrenergic receptor gene (ADRB2; -47 T>C, 46 A>G, 79 C>G, 252 G>A, and 523 C>A) using a single-base extension method.

Results

No significant associations were observed between the genotype/allele frequencies of any of the SNPs tested and any clinical parameters. The haplotype of ADRB2 (GAA composed of 46 A>G, 252 G>A, and 523 C>A) was significantly associated with work-related symptoms (p<0.05). Moreover, in subjects with the AG or GG genotype at 46 A>G and haplotype [GAA] of ADRB2, the prevalence rates of wheat-specific IgG1 antibodies and lower respiratory symptoms increased significantly with exposure intensity (both p<0.05).

Conclusion

The findings of the present study suggest that ADRB2 genetic polymorphism may contribute to the development of work-related symptoms in workers exposed to wheat flour, which can lead to baker''s asthma.     

Caffeine modifies blood glucose availability during prolonged low-intensity exercise in individuals with type-2 diabetes

Objective:

The study investigated the effect of supplementation with maltodextrin (CHO) alone or associated to caffeine during exercise in T2DM subjects.

Methods:

Pilot study, using eight subjects with T2DM, aged 55±10 years, received CHO (1 g/kg) or caffeine (1.5 mg/kg) alone or associated before exercise protocol. The exercise was executed at 40% heart rate (HR) reserve for 40 min, with 10-min recovery. Blood pressure (BP) and perceived exertion scale (Borg) were checked every 2 min. Blood glucose (BG) was checked every 10 min. For statistical analysis, ANOVA test was used and the value was considered statistically significant at p <0.05.

Results:

The results showed that BP and HR did not change significantly among all treatments. Caffeine promoted a significant reduction in BG of 75 mg/dL (65%, p <0.05) during 40 min of exercise protocol compared to all groups.

Conclusion:

Supplementation with 1.5 mg/kg of caffeine reduces BG concentration during prolonged exercise in T2DM patients.     

Angiotensin-converting enzyme gene 2350 G/A polymorphism and susceptibility to atrial fibrillation in Han Chinese patients with essential hypertension

OBJECTIVE:

The angiotensin-converting enzyme gene is one of the most studied candidate genes related to atrial fibrillation. Among the polymorphisms of the angiotensin-converting enzyme gene, the 2350 G/A polymorphism (rs4343) is known to have the most significant effects on the plasma angiotensin-converting enzyme concentration. The aim of the present study was to investigate the association of the angiotensin-converting enzyme 2350 G/A polymorphism with atrial fibrillation in Han Chinese patients with essential hypertension.

METHODS:

A total of 169 hypertensive patients were eligible for this study. Patients with atrial fibrillation (n = 75) were allocated to the atrial fibrillation group, and 94 subjects without atrial fibrillation were allocated to the control group. The PCR-based restriction fragment length polymorphism technique was used to assess the genotype frequencies.

RESULTS:

The distributions of the angiotensin-converting enzyme 2350 G/A genotypes (GG, GA, and AA, respectively) were 40.43%, 41.49%, and 18.08% in the controls and 18.67%, 46.67%, and 34.66% in the atrial fibrillation subjects (p = 0.037). The frequency of the A allele in the atrial fibrillation group was significantly greater than in the control group (58.00% vs. 38.83%, p = 0.0007). Compared with the wild-type GG genotype, the GA and AA genotypes had an increased risk for atrial fibrillation. Additionally, atrial fibrillation patients with the AA genotype had greater left atrial dimensions than the patients with the GG or GA genotypes (p<0.01 and p<0.05, respectively).

CONCLUSIONS:

The results obtained in this study indicate that the angiotensin-converting enzyme 2350 G/A polymorphism is associated with atrial fibrillation and that the A allele shows an increased risk for atrial fibrillation in Han Chinese patients with essential hypertension.     

Lack of Association of the APOE ε4 Allele with the Risk of Obstructive Sleep Apnea: Meta-Analysis and Meta-Regression

Study Objectives:

Reports on the association of polymorphisms in the gene encoding apolipoprotein E (APOE)—a vital macromolecule in cholesterol metabolism—with obstructive sleep apnea (OSA) have provided conflicting results. Our objective was to meta-analytically synthesize the existing evidence for the association of the APOE ε4 allele with the risk of OSA.

Design:

Random effects meta-analysis and meta-regression

Setting:

Genetic epidemiological studies reporting the association of APOE ε4 allele with OSA susceptibility.

Patients or Participants:

Synthesis of APOE ε4 allele data from 6,508 subjects including 1,901 cases of OSA and 4,607 controls.

Interventions:

None

Measurements and Results:

Eight studies were included in the random effects meta-analysis; the summary effect size measured as odds ratio (OR) for association of the APOE ε4 allele with the risk of OSA was found to be 1.13 (95% confidence interval 0.86–1.47). There was a statistically significant heterogeneity (I² = 72%, P = 0.001) across study results that was not explained by the mean age, proportion of males, or the proportion possessing the APOE ε4 allele or when grouped based on the geographic location of the study.

Conclusions:

The hypothesis that the APOE ε4 allele may be causally associated with OSA cannot be supported on the basis of published literature.

Citation:

Thakre TP; Mamtani MR; Kulkarni H. Lack of association of the APOE ε4 allele with the risk of obstructive sleep apnea: meta-analysis and meta-regression. SLEEP 2009;32(11):1507-1511.     

The effect of Nigella sativa extract on tracheal responsiveness and lung inflammation in ovalbumin-sensitized guinea pigs

OBJECTIVE:

To examine the preventive effect of a hydro-ethanolic extract of Nigella sativa on the tracheal responsiveness and white blood cell count in the lung lavage fluid of sensitized guinea pigs.

METHODS:

Three groups of guinea pigs sensitized to intraperitoneally injected and inhaled ovalbumin were given drinking water alone (group S), drinking water containing a low concentration of N. sativa extract (group S+LNS) or drinking water containing a high concentration of N. sativa extract (group S+HNS). The tracheal responses of control animals (group C) and the three groups of sensitized guinea pigs (n = 7 for all groups) to methacholine were measured by the assessment of the tracheal smooth muscle response to increasing concentrations of methacholine, and the effective concentration causing 50% of the maximum response (EC₅₀) was determined. Tracheal responses to 0.1% ovalbumin and white blood cell counts in the lung lavage fluid were also examined.

RESULTS:

The tracheal response of the group S guinea pigs to both methacholine and ovalbumin was significantly higher than the response of the controls (p<0.01 for both cases). The tracheal responses of the S+LNS and S+HNS groups to both methacholine and ovalbumin were significantly decreased compared to those of the S group (p<0.05 to p<0.01). The total white blood cell and eosinophil counts in the lung lavage fluid of group S were significantly higher than those of group C (p<0.01). The white blood cell counts in both treated groups showed significant improvements (p<0.01 for both cases).

CONCLUSIONS:

These results demonstrate the preventive effect of the N. sativa extract on the tracheal response and lung inflammation in sensitized guinea pigs.     

A clinical,microbiological and immunological comparison between subgingival irrigation with Dentol? and chlorhexidine in advanced periodontitis

Introduction

The purpose of this study was to compare the clinical, microbiological and immunological effects of subgingival irrigation with Dentol^™ and 0.2% chlorhexidine in human advanced periodontitis.

Material and methods

Twenty cases of advanced periodontitis patients were randomly treated either with Dentol^™ (as test) or 0.2% chlorhexidine (as control) every other day for 29 days after primary scaling, root planing and oral hygiene instruction. Pocket depth (PD), bleeding on probing (BOP) and plaque index (PI) were considered as clinical parameters. Total counts of aerobic and anaerobic bacteria were measured in subgingival plaque. At the end, concentrations of TNF-α and IL-1β in gingival crevicular fluid were measured as inflammatory markers.

Results

PD and BOP decreased in both groups on the 29^th day and two weeks afterward. PI did not show any statistical difference either within or among groups (p > 0.05). Results indicate that both chlorhexidine and Dentol^™ diminished total count of subgingival anaerobic bacteria significantly (p < 0.05). Total count of subgingival aerobic bacteria increased in both groups, but the differences between the two groups were statistically significant in favour of Dentol^™ (p < 0.05). The level of IL-1β in the crevicular fluid was reduced in both groups but it was more significant in the test group (p < 0.05). The TNF-a level decreased in both groups but the statistical difference between the two groups was negligible (p > 0.05).

Conclusions

Subgingivally irrigation with Dentol^™, containing 0.02% carvacrol, every other day for 29 days is equally or more effective than 0.2% chlorhexidine in reducing clinical and immunological inflammatory indices.     

Novel nonsense mutation of BRCA2 gene in a Moroccan man with familial breast cancer

Background

Breast cancer is the most common cancer in women worldwide. About 5 to 10% of cases are due to an inherited predisposition in two major genes, BRCA1 and BRCA2, transmitted as an autosomal dominant form. Male breast cancer is rare and is mainly due to BRCA2 than BRCA1 germline mutations.

Objective

Molecular study of BRCA2 gene in man with familial breast cancer.

Methods

PCR and direct sequencing of BRCA2 gene.

Results

Identification of novel heterozygous germline mutation c.6428C>A ; p.Ser2143Stop of BRCA2 gene.     

The Relationship between Gastric Juice Nitrate/Nitrite Concentrations and Gastric Mucosal Surface pH

Purpose

To investigate gastric juice nitrate/nitrite concentration according to mucosal surface pH extent (area) of gastric corpus intimately contacting the gastric juice.

Materials and Methods

We included ninety-nine patients with dyspepsia. To evaluate gastric mucosal surface pH and its extent, gastric chromosocpy was performed by spraying phenol red dye on the corpus mucosa and estimating the extent of area with color changed. Nitrate/nitrite concentrations and pH of gastric juice were measured by ELISA and pH meter, respectively. Silver staining was done to histologically confirm the presence of Helicobacter pylori.

Results

Intragastric nitrate/nitrite concentrations in patients, showing phenol red staining mucosa were higher than those of unstaining mucosa (p=0.001): the more extensive in the area of phenol red staining area of corpus, the higher gastric juice pH found (r=0.692, p<0.001). Furthermore, the intragastric nitrate/nitrite concentrations correlated positively with gastric juice pH (r=0.481, p<0.001).

Conclusion

The changes of mucosal surface pH and its extent in gastric corpus might affect either pH or nitrate/nitrite level of gastric juice.     

Candida species and other yeasts in the oral cavities of type 2 diabetic patients in Cali,Colombia

Objective:

To determine the prevalence of Candida species and to study factors associated to oral cavity colonization in patients with type 2 diabetes mellitus.

Methods:

A total of 107 diabetics were classified into controlled and uncontrolled according to glycosylated hemoglobin values. Each patient was assessed for stimulated salivary flow rates, pH, and an oral rinse to search for yeast. The study also determined the state of oral health via Klein and Palmer CPO indexes for permanent dentition, dental plaque by O''Leary, and a periodontal chart.

Results:

We found yeasts in 74.8% of the patients. A total of 36 of the 52 subjects with controlled diabetes presented yeasts and 44 in the uncontrolled; no significant differences (p = 0.2) were noted among the presence of yeasts and the control of blood glucose. The largest number of isolates corresponded to C. albicans, followed by C. parapsilosis. Uncontrolled individuals presented a significantly higher percentage of yeast different from C. albicans (p = 0.049).

Conclusions:

We found a high percentage of Candida colonization and uncontrolled individuals had greater diversity of species. The wide range of CFU/mL found both in patients with oral candidiasis, as well as in those without it did not permit distinguishing between colonization and disease. We only found association between isolation of yeasts and the low rate of salivary flow.     

Cyclooxygenase-2 Polymorphisms and Susceptibility to Colorectal Cancer: A Meta-Analysis

Purpose

Four polymorphisms, -765G>C, -1195G>A, 8473T>C, and Val511Ala, in the cyclooxygenase-2 (COX-2) gene were identified to be associated with colorectal cancer (CRC) risk. However, the results are inconsistent. The objective of this meta-analysis was to evaluate the association between these four polymorphisms and the risk of CRC.

Materials and Methods

All eligible case-control studies published up to December 2012 on the association between the four polymorphisms of COX-2 and CRC risk were identified by searching PubMed and Web of Science. The CRC risk associated with the four polymorphisms of the COX-2 gene was estimated for each study by odds ratio (OR) together with its 95 % confidence interval (CI), respectively.

Results

A total of 15 case-control studies were included. Overall, no evidence has indicated that the -1195A allele, -765C allele, 8473C allele, and 511Ala allele are associated with susceptibility to CRC (-1195G>A: OR=1.11, 95 % CI: 0.82-1.51, p=0.78; -765G>C: OR=1.08, 95 % CI: 0.96-1.21, p=0.07; 8473T>C: OR=1.03, 95 % CI: 0.89-1.18, p=0.91; Val511Ala: OR=0.71, 95 % CI: 0.46-1.09, p=0.94). However, stratified analysis with ethnicity indicated that individuals with -765GC or GC/CC genotypes had an increased risk of CRC among Asian populations (GC vs. GG: OR=1.05, 95 % CI: 0.87-1.28, p=0.03; GC+CC vs. GG: OR=1.08, 95 % CI: 0.96-1.21, p=0.07).

Conclusion

This meta-analysis indicated that -765G>C polymorphism was significantly associated with susceptibility to CRC in Asian populations.     

The HLA-DRB1 Polymorphism is Associated With Atopic Dermatitis, but not Egg Allergy in Korean Children

Purpose

We investigated whether particular HLA-DRB1 polymorphisms contribute to egg allergy development in Korean children with atopic dermatitis (AD).

Methods

HLA-DRB1 alleles were determined by PCR-sequence-specific oligonucleotide (SSO) and PCR-single-strand conformation polymorphism (SSCP) methods in 185 patients with AD and 109 normal control (NC) subjects. AD patients were divided into two groups: 1) AD with egg allergy, consisting of 96 patients with egg allergies as determined by egg-specific immunoglobulin E (IgE) reactivity; and 2) AD without egg allergy, consisting of 89 patients without egg allergies. HLA-DRB1 alleles were classified into functional groups (A, De, Dr, E, Q, R, a). HLA-DRB1 phenotype and functional group frequencies in the AD, AD with egg allergy, and AD without egg allergy groups were compared with those in the NC group.

Results

The frequency of DRB1^*08:02 was decreased in the AD with egg allergy group compared with the AD without egg allergy group (2.1% vs. 10.1%, P=0.021), and DRB1^*15:01 was increased in the AD with egg allergy group compared with the AD without egg allergy group (22.9% vs. 11.2%, P=0.036). However, significance was lost after Bonferroni correction. HLA-DRB1^*11:01 had a significantly higher frequency in AD patients compared with NCs (12.4% vs. 1.8%, corrected P=0.048) and was regarded as a susceptibility factor associated with AD. DRB1^*08:03 was decreased in AD patients compared with NCs (10.8% vs. 19.3%, P=0.043). HLA-DRB1 functional group ''a'', which includes DRB1^*15:01, seemed to be associated with the development of egg allergy in AD (P=0.033), but this result was not significant after Bonferroni correction.

Conclusions

HLA-DRB1 polymorphism is not associated with egg allergy, but HLA-DRB1^*11:01 is associated with AD in Korean children.     

The T/G 13915 variant upstream of the lactase gene (LCT) is the founder allele of lactase persistence in an urban Saudi population

Background

The prevalence of lactase persistence is high in Saudi Arabia.

Objective

To identify a DNA variant for the lactase persistence/non‐persistence trait in adult Arabs in Saudi Arabia.

Methods

We sequenced DNA from 432 anonymous neonatal blood donors from five different regions of Saudi Arabia to cover the 400 bp region surrounding the previously identified lactase persistence/non‐persistence variant C/T−13910 residing in intron 13 of the MCM6 gene.

Results

Two anonymous blood donors carried the C/T−13910 genotype. One variant, T/G −13915, residing 5 bp upstream of the C/T−13910 variant, was present in 332 of 432 (76.9%) of the neonatal samples, compatible with previous prevalence figures of lactase persistence in urban Saudi populations. Determination of disaccharidase activities in 25 intestinal biopsy samples showed a highly significant correlation between lactase activity and the T/G−13915 genotypes (p<0.001; Fisher exact test) as well as between the L:S ratio and the aforementioned genotypes (p<0.001; Fisher exact test).

Conclusion

The T/G−13915 variant is the founder mutation of lactase persistence in an urban Saudi population. The results obtained here have implications for genetic testing of adult‐type hypolactasia and to analysis of human evolution, the origin of cattle domestication and migrations of the populations in the Arabian peninsula.     

Interleukin-10 but not interleukin-18 may be associated with the immune response against well-differentiated thyroid cancer

OBJECTIVES:

The aim of this study was to investigate the role of the interleukin-18 +105A/C and interleukin-10 -1082A/G germline polymorphisms in the development and outcome of differentiated thyroid carcinoma associated or not with concurrent thyroiditis.

METHODS:

We studied 346 patients with differentiated thyroid carcinomas, comprising 292 papillary carcinomas and 54 follicular carcinomas, who were followed up for 12-298 months (mean 76.10±68.23 months) according to a standard protocol. We genotyped 200 patients and 144 control individuals for the interleukin-18 +105A/C polymorphism, and we genotyped 183 patients and 137 controls for the interleukin-10 -1082A/G polymorphism.

RESULTS:

Interleukin-18 polymorphisms were not associated with chronic lymphocytic thyroiditis or any clinical or pathological feature of tumor aggressiveness. However, there was an association between the presence of interleukin-10 variants and chronic lymphocytic thyroiditis. Chronic lymphocytic thyroiditis was present in 21.74% of differentiated thyroid carcinoma patients, most frequently affecting women previously diagnosed with Hashimoto''s thyroiditis who had received a lower ¹³¹I cumulative dose and did not present lymph node metastases.

CONCLUSIONS:

We conclude that the inheritance of a G allele at the interleukin-10 -1082A/G polymorphism may favor a concurrent thyroid autoimmunity in differentiated thyroid carcinoma patients, and this autoimmunity may favor a better prognosis for these patients.