title: Sex-specific effect of Pirin gene on bone mineral density in a cohort of 4000 Chinese.
abstract: BACKGROUND
  Osteoporosis is a common condition among elderly. Genetic mapping studies repeatedly located the distal short arms of X-chromosome as the quantitative trait loci (QTL) for BMD in mice. Fine mapping of a syntenic segment on Xp22 in a Caucasian female population suggested a moderate association between lumbar spine (LS) BMD and 2 intronic SNPs in the Pirin (PIR) gene, which encodes an iron-binding nuclear protein. This study aimed to examine genetic variations in the PIR gene by a comprehensive tagging method and its sex-specific effects on BMD and osteoporotic risk.
  
  
  METHODS
  Two thousand men and 2000 women aged 65 or above were recruited from the community. BMDs at the LS, femoral neck, total hip and whole body were measured and followed up at 4-year. Genotyping was performed for tagSNPs of PIR gene including adjacent regions, and the PIR haplotypes were inferred using PHASE program.
  
  
  RESULTS
  Analysis by linear regression showed a significant association between SNP rs5935970 and LS-BMD, while haplotype T-T-A was significantly associated with BMD of all measured sites. However, none of such associations were found in men. Linear Mixed Model also confirmed the same sex-specific and site-specific effect for longitudinal BMD changes.
  
  
  CONCLUSIONS
  In addition to confirming the association between BMDs and the PIR gene, we also revealed that this finding is sex-specific, possibly due to an X-linked effect. This study demonstrated the importance of considering sex and genetic interactions in studies of disease predisposition and complex traits.
authors.affiliation: Department of Chemical Pathology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China. nelsontang@cuhk.edu.hk
authors.forename: Nelson L S
authors.initials: NL
authors.lastname: Tang
authors.forename: Chen Di
authors.initials: CD
authors.lastname: Liao
authors.forename: Jasmine K L
authors.initials: JK
authors.lastname: Ching
authors.forename: Eddie W C
authors.initials: EW
authors.lastname: Suen
authors.forename: Iris H S
authors.initials: IH
authors.lastname: Chan
authors.forename: Eric
authors.initials: E
authors.lastname: Orwoll
authors.forename: Suzanne C
authors.initials: SC
authors.lastname: Ho
authors.forename: Frank W K
authors.initials: FW
authors.lastname: Chan
authors.forename: Anthony W L
authors.initials: AW
authors.lastname: Kwok
authors.forename: Timothy
authors.initials: T
authors.lastname: Kwok
authors.forename: Jean
authors.initials: J
authors.lastname: Woo
authors.forename: Ping Chung
authors.initials: PC
authors.lastname: Leung
mesh_terms: D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D015519:Bone Density / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D002681:China; D015331:Cohort Studies; D049308:Dioxygenases; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D016014:Linear Models; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012727:Sex Characteristics
chemical_list: D002352:Carrier Proteins; D009687:Nuclear Proteins; D049308:Dioxygenases; C105340:PIR protein, human