PMID- 17142250
OWN - NLM
STAT- MEDLINE
DCOM- 20070426
LR  - 20101118
IS  - 0964-6906 (Print)
IS  - 0964-6906 (Linking)
VI  - 16
IP  - 3
DP  - 2007 Feb 1
TI  - Sex-specific linkage to total serum immunoglobulin E in families of children with 
      asthma in Costa Rica.
PG  - 243-53
AB  - Serum total immunoglobulin E (IgE) is a critical intermediate phenotype of 
      allergic diseases. Although total IgE exhibits sexual dimorphism in humans (with 
      males demonstrating higher IgE than females), the molecular basis of this 
      difference is unknown. A genome-wide scan of 380 short-tandem repeat (STR) 
      markers was performed in eight extended pedigrees of asthmatic children (n=655) 
      from the Central Valley of Costa Rica. Genome-wide linkage analysis of total IgE 
      was performed by variance component models. Among all subjects, only one genomic 
      region (chromosome 7p15) showed modest evidence of linkage to total IgE 
      (LOD=1.60). In contrast, a sex-stratified analysis revealed distinct genetic 
      architectures of total IgE in males and females and identified significant 
      linkage to total IgE on a novel male-specific locus on chromosome 20p12 (LOD=3.63 
      at 36 cM). Genotyping of additional STRs on chromosome 20 resulted in improved 
      evidence for linkage (LOD=3.75 at 33 cM) and a 1.5 LOD-unit support interval for 
      the linkage peak between 26 and 38 cM. Three polymorphisms in two genes on 
      chromosome 20p12 (JAG1 and ANKRD5) were then found to be associated with total 
      IgE in 420 nuclear families of Costa Rican children with asthma. Two of these 
      polymorphisms (in JAG1) were significantly associated with total IgE in families 
      of boys (n=264) but not in families of girls (n=156) with asthma. JAG1 is a 
      hematopoetic cell growth factor that may regulate normal B-cell development. This 
      is the first demonstration of a possible genetic basis for differences in total 
      IgE between sexes.
FAU - Raby, Benjamin A
AU  - Raby BA
AD  - Channing Laboratory and Respiratory Disorders Program, Department of Medicine, 
      Brigham and Women's Hospital, 181 Longwood Avenue, Boston, MA 02115, USA.
FAU - Soto-Quiros, Manuel E
AU  - Soto-Quiros ME
FAU - Avila, Lydiana
AU  - Avila L
FAU - Lake, Stephen L
AU  - Lake SL
FAU - Murphy, Amy
AU  - Murphy A
FAU - Liang, Catherine
AU  - Liang C
FAU - Fournier, Eduardo
AU  - Fournier E
FAU - Spesny, Mitzi
AU  - Spesny M
FAU - Sylvia, Jody S
AU  - Sylvia JS
FAU - Verner, Andrei
AU  - Verner A
FAU - Hudson, Thomas J
AU  - Hudson TJ
FAU - Klanderman, Barbara J
AU  - Klanderman BJ
FAU - Freimer, Nelson B
AU  - Freimer NB
FAU - Silverman, Edwin K
AU  - Silverman EK
FAU - Celedon, Juan C
AU  - Celedon JC
LA  - eng
GR  - HL04370/HL/NHLBI NIH HHS/United States
GR  - HL66289/HL/NHLBI NIH HHS/United States
GR  - K08 HL074193/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20061201
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
RN  - 37341-29-0 (Immunoglobulin E)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Asthma/*blood/*genetics
MH  - Child
MH  - Chromosome Mapping
MH  - Chromosomes, Human, Pair 20
MH  - Costa Rica
MH  - *Family
MH  - Female
MH  - *Genetic Linkage
MH  - Genome, Human
MH  - Humans
MH  - Immunoglobulin E/*blood
MH  - Male
MH  - Middle Aged
MH  - *Sex Characteristics
EDAT- 2006/12/05 09:00
MHDA- 2007/04/27 09:00
CRDT- 2006/12/05 09:00
PHST- 2006/12/05 09:00 [pubmed]
PHST- 2007/04/27 09:00 [medline]
PHST- 2006/12/05 09:00 [entrez]
AID - ddl447 [pii]
AID - 10.1093/hmg/ddl447 [doi]
PST - ppublish
SO  - Hum Mol Genet. 2007 Feb 1;16(3):243-53. doi: 10.1093/hmg/ddl447. Epub 2006 Dec 1.