PMID- 22648180
OWN - NLM
STAT- MEDLINE
DCOM- 20121127
LR  - 20221207
IS  - 1435-232X (Electronic)
IS  - 1434-5161 (Linking)
VI  - 57
IP  - 7
DP  - 2012 Jul
TI  - Association of variants in genes involved in environmental chemical metabolism 
      and risk of cryptorchidism and hypospadias.
PG  - 434-41
LID - 10.1038/jhg.2012.48 [doi]
AB  - We hypothesized that single-nucleotide polymorphisms (SNPs) of genes involved in 
      environmental endocrine disruptors (EEDs) metabolism might influence the risk of 
      male genital malformations. In this study, we explored for association between 
      384 SNPs in 15 genes (AHR, AHRR, ARNT, ARNT2, NR1I2, RXRA, RXRB, RXRG, CYP1A1, 
      CYP1A2, CYP1B1, CYP2B6, CYP3A4, CYP17A1 and CYP19A1) and risk of cryptorchidism 
      (CO) and hypospadias (HS) in 334 Japanese (JPN) males (141 controls, 95 CO and 98 
      HS) and 187 Italian (ITA) males (129 controls and 58 CO). In the JPN study group, 
      five SNPs from ARNT2 (rs2278705 and rs5000770), CYP1A2 (rs2069521), CYP17A1 
      (rs4919686) and NR1I2 (rs2472680) were significantly associated at both allelic 
      and genotypic levels with risk of at least one genital malformation phenotype. In 
      the ITA study group, two SNPs in AHR (rs3757824) and ARNT2 (rs1020397) were 
      significantly associated with risk of CO. Interaction analysis of the positive 
      SNPs using multifactor dimensionality reduction demonstrated that synergistic 
      interaction between rs2472680, rs4919686 and rs5000770 had 62.81% prediction 
      accuracy for CO (P=0.011) and that between rs2069521 and rs2278705 had 69.98% 
      prediction accuracy for HS (P=0.001) in JPN population. In a combined analysis of 
      JPN and ITA population, the most significant multi-locus association was observed 
      between rs5000770 and rs3757824, which had 65.70% prediction accuracy for CO 
      (P=0.055). Our findings indicate that genetic polymorphisms in genes involved in 
      EED metabolism are associated with risk of CO and HS.
FAU - Qin, Xian-Yang
AU  - Qin XY
AD  - Research Center for Environmental Risk, National Institute for Environmental 
      Studies, Tsukuba, Ibaraki, Japan.
FAU - Kojima, Yoshiyuki
AU  - Kojima Y
FAU - Mizuno, Kentaro
AU  - Mizuno K
FAU - Ueoka, Katsuhiko
AU  - Ueoka K
FAU - Massart, Francesco
AU  - Massart F
FAU - Spinelli, Claudio
AU  - Spinelli C
FAU - Zaha, Hiroko
AU  - Zaha H
FAU - Okura, Masahiro
AU  - Okura M
FAU - Yoshinaga, Jun
AU  - Yoshinaga J
FAU - Yonemoto, Junzo
AU  - Yonemoto J
FAU - Kohri, Kenjiro
AU  - Kohri K
FAU - Hayashi, Yutaro
AU  - Hayashi Y
FAU - Ogata, Tsutomu
AU  - Ogata T
FAU - Sone, Hideko
AU  - Sone H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120531
PL  - England
TA  - J Hum Genet
JT  - Journal of human genetics
JID - 9808008
RN  - 0 (ARNT2 protein, human)
RN  - 0 (Basic Helix-Loop-Helix Transcription Factors)
RN  - 0 (ESR1 protein, human)
RN  - 0 (Endocrine Disruptors)
RN  - 0 (Estrogen Receptor alpha)
RN  - 138391-32-9 (Aryl Hydrocarbon Receptor Nuclear Translocator)
RN  - EC 1.14.14.1 (CYP1A2 protein, human)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1A2)
RN  - EC 1.14.14.19 (CYP17A1 protein, human)
RN  - EC 1.14.14.19 (Steroid 17-alpha-Hydroxylase)
SB  - IM
CIN - J Hum Genet. 2012 Jul;57(7):405-6. PMID: 22695890
MH  - Adolescent
MH  - Aryl Hydrocarbon Receptor Nuclear Translocator/genetics/metabolism
MH  - Asian People/genetics
MH  - Basic Helix-Loop-Helix Transcription Factors/genetics/metabolism
MH  - Case-Control Studies
MH  - Child
MH  - Child, Preschool
MH  - Cryptorchidism/epidemiology/*genetics
MH  - Cytochrome P-450 CYP1A2/genetics/metabolism
MH  - Endocrine Disruptors/*metabolism
MH  - Estrogen Receptor alpha/genetics/metabolism
MH  - Gene Frequency
MH  - *Gene-Environment Interaction
MH  - Genetics, Population
MH  - Humans
MH  - Hypospadias/epidemiology/*genetics
MH  - Infant
MH  - Italy
MH  - Japan
MH  - Male
MH  - Polymorphism, Single Nucleotide
MH  - Risk Factors
MH  - Steroid 17-alpha-Hydroxylase/genetics/metabolism
MH  - White People/genetics
EDAT- 2012/06/01 06:00
MHDA- 2012/12/10 06:00
CRDT- 2012/06/01 06:00
PHST- 2012/06/01 06:00 [entrez]
PHST- 2012/06/01 06:00 [pubmed]
PHST- 2012/12/10 06:00 [medline]
AID - jhg201248 [pii]
AID - 10.1038/jhg.2012.48 [doi]
PST - ppublish
SO  - J Hum Genet. 2012 Jul;57(7):434-41. doi: 10.1038/jhg.2012.48. Epub 2012 May 31.