Association of ALOX12 and ALOX15 gene polymorphisms with age at menarche and natural menopause in Chinese women.
OBJECTIVE
Lipoxygenase (LOX) is one of the major metabolic enzymes for arachidonic acid, which has been reported to be associated with many postmenopausal and many hormone-related diseases. In rats, selective inhibition of the LOX pathway led to defective ovulation. However, little is known about the association of the LOX-related genes with menstruation in women. In this study, we investigated the possible association of two key gene (ALOX12 and ALOX15) polymorphisms with age of menarche and menopause in Chinese women.


METHODS
Six tagging single nucleotide polymorphisms (SNPs) of ALOX12 and five SNPs of ALOX15 were genotyped. The association of single SNPs and haplotypes in two candidate genes and age at menarche (AAM) variation was tested in 401 Chinese nuclear families using the quantitative transmissing disequilibrium test. Furthermore, the association between these SNPs and haplotypes and age at natural menopause (AANM) in 710 postmenopausal Chinese women was measured.


RESULTS
Using family- and population-based statistical procedures, significant association was found between SNPs rs312462 in ALOX12 and AAM in nuclear families (P = 0.043), and three SNPs (rs2292350, rs312470, and rs312462) in ALOX12 were significantly associated with AANM in postmenopausal women (P = 0.012, P = 0.045, and P = 0.033, respectively). Haplotype analyses corroborated our single SNP results (P = 0.030). However, we failed to find a significant association between ALOX15 gene polymorphisms and AAM as well as AANM (P > 0.05).


CONCLUSIONS
Our present results suggest that genetic variations in ALOX12 are associated with both the onset and cessation of menstruation in Chinese women living in Shanghai.
Metabolic Bone Disease and Genetics Research Unit, Department of Osteoporosis and Bone Diseases, The Shanghai Sixth People's Hospital, Shanghai Jiaotong University, Shanghai, China.
Wenjin
W
Xiao
Yaohua
Y
Ke
Jinwei
J
He
Hao
H
Zhang
Jinbo
J
Yu
Weiwei
W
Hu
Jiemei
J
Gu
Hua
H
Yue
Chun
C
Wang
Yunqiu
Y
Hu
Miao
M
Li
Wenzhen
W
Fu
Yujuan
Y
Liu
Zhenlin
Z
Zhang
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001092:Arachidonate 12-Lipoxygenase / Q000235:genetics*; D001093:Arachidonate 15-Lipoxygenase / Q000235:genetics*; D044466:Asian People; D002681:China; D005220:Fathers; D005260:Female; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008572:Menarche / Q000235:genetics*; D008593:Menopause / Q000235:genetics*; D008875:Middle Aged; D009035:Mothers; D009679:Nuclear Family; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
D001092:Arachidonate 12-Lipoxygenase; C476558:ALOX12 protein, human; C515716:ALOX15 protein, human; D001093:Arachidonate 15-Lipoxygenase