Hau Chuang

Polymorphism of the immune-braking gene CTLA-4 (+49) involved in gender discrepancy of serum total IgE levels and allergic diseases

Background A variety of genes are related to allergic disorders in different ethnic populations. The genetic basis for the gender discrepancy of allergic diseases remains to be determined.

Prenatal and postnatal probiotics reduces maternal but not childhood allergic diseases: a randomized, double‐blind, placebo‐controlled trial

The prevalence of atopic diseases has increased rapidly in recent decades globally. The administration of probiotics to reduce gastrointestinal inflammation has been popular, but its role in the prevention or treatment of allergic disease remains controversial. This study evaluated the effectiveness of prenatal and postnatal probiotics in the prevention of early childhood and maternal allergic diseases.

MicroRNA‐21 expression in neonatal blood associated with antenatal immunoglobulin E production and development of allergic rhinitis

Background The prevalence of allergic diseases has increased in the past decades. It is unknown whether expression of certain microRNAs (miRNAs) in neonatal leucocytes is correlated to IgE production and/or allergic diseases.

Gene–gene and gene–environment interactions on IgE production in prenatal stage

To cite this article: Yang KD, Chang J‐C, Chuang H, Liang H‐M, Kuo H‐C, Lee Y‐S, Hsu T‐Y, Ou C‐Y. Gene–gene and gene–environment interactions on IgE production in prenatal stage. Allergy 2010; 65: 731–739.

Gender‐limited association of cytotoxic T‐lymphocyte antigen‐4 (CTLA‐4) polymorphism with cord blood IgE levels

Allergic mechanism has long been attributed to IgE‐mediated reaction. The relationship between gene polymorphism and cord blood IgE (CB IgE) is unclear. We investigated whether elevation of CB IgE levels was associated with polymorphisms of cytotoxic T‐lymphocyte antigen 4 (CTLA‐4) at (−318) CT and (+49) AG positions in a gender‐limited fashion. CB IgE levels were determined by Pharmacia CAP system and the CTLA‐4 polymorphisms at (−318) and (+49) were determined by restriction fragment length polymorphism (RFLP). A total of 644 consecutive umbilical cord bloods were collected for this study. 32.9% of newborn infants had detectable IgE levels (≥0.35 kU/l). 25.6% of the male newborns had elevated CB IgE levels (≥0.5 kU/l) similar to those of the female newborns (22.7%). The CTLA‐4 polymorphism at (+49) but not (−318) was significantly associated with elevated CB IgE levels (p = 0.004). The association of CTLA‐4 (+49) A allele with elevated CB IgE levels was found only in females. Both male and female infants with different CTLA‐4 (−318) genotypes had no difference in the rates of elevated CB IgE levels. A linkage disequilibrium between CTLA‐4 (+49) G and (−318) C allele was found in this Chinese population. Subjects with the (+49, GG and −318, CC) genotype had a significantly lower rate of elevated CB IgE levels. Association of the CTLA‐4 (+49) polymorphism with elevated CB IgE levels was found only in female infants. Newborn infants with the (+49, GG and −318, CC) genotype tended to have a low rate of elevated CB IgE.

Interaction of maternal atopy, CTLA‐4 gene polymorphism and gender on antenatal immunoglobulin E production

Background Genetic heritability and maternal atopy have been correlated to antenatal IgE production, but very few studies have studied gene–maternal atopy interaction on antenatal IgE production. This study investigated the interaction of CTLA‐4 polymorphism with prenatal factors on the elevation of cord blood IgE (CBIgE).

Partial Protein-Hydrolyzed Infant Formula Decreased Food Sensitization but Not Allergic Diseases in a Prospective Birth Cohort Study

Background: Exposure to cow’s milk protein in early infancy could lead to increased rates of allergic diseases later in life. We investigated whether feeding a protein-hydrolyzed formula (HF) in the first 6 months of life decreased allergic diseases up to 36 months later. Methods: Newborns who had at least 1 first-degree family member with a history of atopy and could not breast-feed were enrolled. They were fed with HF or cow’s milk infant formula (CM) for at least 6 months via an open-label protocol and were monitored prospectively at 6, 18 and 36 months of age to assess allergy sensitization and allergic diseases. Results: A total of 1,002 infants were enrolled and 679 infants were consistently fed the same formula for the first 6 months of life (345 HF and 334 CM). The percentage of food sensitization (especially to milk protein) was significantly lower in the HF group than in the CM group at 36 months (12.7 vs. 23.4%, p = 0.048). There was no significant difference in the prevalence of aeroallergen sensitization between the groups. Occurrence of allergic diseases during the first 3 years of life was significantly correlated with aeroallergen sensitization, but not to food allergen sensitization, parental atopy or feeding types. Conclusions: Infants fed with HF during the first 6 months of life had a significantly lower percentage of sensitization to milk protein allergens, but not allergic diseases during the first 3 years of life. Avoidance of cow’s milk protein alone in infancy is not enough to decrease rates of allergic diseases.

Different genetic associations of the IgE production among fetus, infancy and childhood.

Elevation of serum IgE levels has long been associated with allergic diseases. Many genes have been linked to IgE production, but few have been linked to the developmental aspects of genetic association with IgE production. To clarify developmental genetic association, we investigated what genes and gene-gene interactions affect IgE levels among fetus, infancy and childhood in Taiwan individuals. A birth cohort of 571 children with completion of IgE measurements from newborn to 1.5, 3, and 6 years of age was subject to genetic association analysis on the 384-customized SNPs of 159 allergy candidate genes. Fifty-three SNPs in 37 genes on innate and adaptive immunity, and stress and response were associated with IgE production. Polymorphisms of the IL13, and the HLA-DPA1 and HLA-DQA1 were, respectively, the most significantly associated with the IgE production at newborn and 6 years of age. Analyses of gene-gene interactions indentified that the combination of NPSR1, rs324981 TT with FGF1, rs2282797 CC had the highest risk (85.7%) of IgE elevation at 1.5 years of age (P = 1.46×10−4). The combination of IL13, CYFIP2 and PDE2A was significantly associated with IgE elevation at 3 years of age (P = 5.98×10−7), and the combination of CLEC2D, COLEC11 and CCL2 was significantly associated with IgE elevation at 6 years of age (P = 6.65×10−7). Our study showed that the genetic association profiles of the IgE production among fetus, infancy and childhood are different. Genetic markers for early prediction and prevention of allergic sensitization may rely on age-based genetic association profiles.

A prospective birth cohort study of different risk factors for development of allergic diseases in offspring of non-atopic parents

Background: Allergic diseases are thought to be inherited. Prevalence of allergic diseases has, however, increased dramatically in last decades, suggesting environmental causes for the development of allergic diseases. Objective: We studied risk factors associated with the development of atopic dermatitis (AD), allergic rhinitis (AR) and asthma (AS) in children of non-atopic parents in a subtropical country. Methods: In a birth cohort of 1,497 newborns, parents were prenatally enrolled and validated for allergic diseases by questionnaire, physician-verified and total or specific Immunoglobulin E (IgE) levels; 1,236 and 756 children, respectively, completed their 3-year and 6-year follow-up. Clinical examination, questionnaire, and blood samples for total and specific IgE of the children were collected at each follow-up visit. Results: Prevalence of AD, AR and AS was, respectively, 8.2%, 30.8% and 12.4% in children of non-atopic parents. Prevalence of AR (p<.001) and AS (p=.018) was significantly higher in children of parents who were both atopic. A combination of Cesarean section (C/S) and breastfeeding for more than 1 month showed the highest risk for AD (OR=3.111, p=.006). Infants living in homes with curtains and no air filters had the highest risk for AR (OR=2.647, p<.001), and male infants of non-atopic parents living in homes without air filters had the highest risk for AS (OR=1.930, p=.039). Conclusions: Breastfeeding and C/S affect development of AD. Gender, use of curtains and/or air filters affect AR and AS, suggesting that control of the perinatal environment is necessary for the prevention of atopic diseases in children of non-atopic parents.

Prevalence of infant sneezing without colds and prediction of childhood allergy diseases in a prospective cohort study

Background Allergy sensitization may begin during the perinatal period, but predicting allergic diseases in infancy remains difficult. This study attempted to identify early predictors of childhood allergy diseases in a prospective cohort study. Materials and Methods In a prospective birth cohort study at southern Taiwan locating in a subtropical region, questionnaire surveys of sneezing or cough without colds at 6 and 18 months of age were recorded, and the correlation with allergy diseases was assessed at 3 and 6 years of age. Results A total of 1812 pregnant women and 1848 newborn infants were prenatally enrolled, and 1543, 1344, 1236, and 756 children completed the follow-up at ages 6 months, 18 months, 3 years and 6 years, respectively. The prevalence of infant sneezing without colds at 6 and 18 months of age was 30.3% and 19.2%, respectively. The prevalence of infant cough without colds at 6 and 18 months of age was 10.6% and 5.7%, respectively. Infant sneezing without colds at 18 months of age was significantly correlated with atopic dermatitis, allergic rhinitis and asthma at 6 years of age. Infant cough without colds at 18 months of age significantly predicted asthma but not atopic dermatitis or allergic rhinitis at 6 years of age. Conclusions Infant sneezing without colds predicted all allergy diseases at 6 years of age in a subtropical country. This highlights a potential non-invasive clue in a subtropical region for the early prediction, treatment and prevention of childhood allergy diseases in infancy.