The association of maternal but not paternal genetic variation in GSTP1 with asthma phenotypes in children.
Maternal factors including atopy and smoking during pregnancy are associated with asthma risk during childhood. Suggested mechanisms include transmission of specific maternal alleles and maternal influences on the intrauterine environment. We have previously shown that polymorphism in glutathione S-transferase, GSTP1 is associated with airway hyperresponsiveness (AHR) and atopy in adults. We now hypothesise that GSTP1 genotypes in the mother and child, but not the father, mediate asthma phenotypes in the child. One hundred and forty-five Caucasian families were recruited via an asthmatic proband aged 7-18 years. Atopy and asthma were assessed using a questionnaire, skin prick testing, serum IgE, spirometry and methacholine challenge (PC20, dose-response slope--DRS). GSTP1 genotyping was determined using PCR. GSTP1 Val105/Val105 genotype in the child was associated with a reduced risk of atopy (P = 0.038) and AHR (PC20, P = 0.046; DRS, P = 0.032). In mothers (P = 0.014) but not fathers (P = 0.623), Val105/Val105 was associated with a reduced risk of AHR in the child. We have identified, for the first time, an association between maternal genotype and the child's asthma phenotype that appears not to be due to transmission of specific maternal alleles. This preliminary data supports the view of in utero effects of maternal genotype and adds new insights into the possible mechanisms by which maternal factors may influence development of childhood asthma.
Child
Frances
F
Academic Department of Child Health, University Hospital of North Staffordshire, Newcastle Road, Stoke on Trent ST4 6QG, UK.
Lenney
Warren
W
Clayton
Sadie
S
Davies
Siobhan
S
Jones
Peter W
PW
Alldersea
Julie E
JE
Strange
Richard C
RC
Fryer
Anthony A
AA
D000293:Adolescent; D001249:Asthma / Q000235:genetics* / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000235:genetics / Q000503:physiopathology; D002648:Child; D005220:Fathers; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D005838:Genotype; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000235:genetics / Q000503:physiopathology; D007527:Isoenzymes / Q000235:genetics*; D008297:Male; D009035:Mothers; D010641:Phenotype; D011247:Pregnancy; D011248:Pregnancy Complications; D011297:Prenatal Exposure Delayed Effects; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D014797:Vital Capacity / Q000502:physiology
D007527:Isoenzymes; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase