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.
From the 1Metabolic Bone Disease and Genetics Research Unit, Department of Osteoporosis and Bone Diseases, The Shanghai Sixth People’s Hospital, Shanghai Jiaotong University, Shanghai, China; and 2Department of Endocrinology, Second Affiliated Hospital of Soochow University, Suzhou, China.
Received November 2, 2011; revised and accepted February 2, 2012.
Funding/support: This study was supported by the National Natural Science Foundation of China (Grants 30771019, 30570819, 30800387, 81070692, 81000360, and 81170803), the Program of Shanghai SubjectChief Scientist (Grant 08XD1403000), the Science and Technology commission of Shanghai municipality (10D21950100 and 08411963100), and Academic Leaders in Health Sciences in Shanghai (XBR2011014).
Financial disclosure/conflicts of interest: None reported.
Address correspondence to: Zhenlin Zhang, PhD, Department of Osteoporosis, Metabolic Bone Disease and Genetic Research Unit, Shanghai Jiao Tong University Affiliated Sixth People_s Hospital. Shanghai, 600 Yi-Shan Rd, Shanghai 200233, P. R. China. E-mail: firstname.lastname@example.org