title: CREM variants rs4934540 and rs2295415 conferred susceptibility to nonobstructive azoospermia risk in the Chinese population.
abstract: To evaluate the association of variants related to spermatogenesis with susceptibility to Chinese idiopathic nonobstructive azoospermia (NOA), seventeen tag single-nucleotide polymorphisms (SNPs) in CREM, ACT, KIF17b, and SPAG8 were analyzed in 361 NOA patients and 368 controls by Sequenom iplex technology. The results showed that two CREM SNPs, rs4934540 and rs22954152, were significantly associated with NOA and played protective roles against the disease (P value with Bonferroni correction = 0.00017, odds ratio [OR] = 0.624 and P = 0.012, OR = 0.686, respectively). Haplotype analysis of CREM gene variants suggested that haplotype CGTG of the SNPs, rs4934540, rs2295415, rs11592356, and rs1148247, exhibited significant protective effect against the occurrence of NOA (P = 0.001, OR = 0.659). The haplotype TATG conferred a significantly increased risk of NOA (P = 0.011, OR = 1.317). Furthermore, making use of quantitative RT-PCR, we demonstrated that relative mRNA expression of CREM in NOA patients with maturation arrest was only one-third of that in the controls with normal spermatogenesis (P < 0.0001). Our findings indicated that the polymorphisms of CREM gene were associated with NOA in the Chinese population and low CREM expression might be involved in the pathogenesis of spermatogenesis maturation arrest.
authors.affiliation: Reproductive Medicine Center, The First Affiliated Hospital of Anhui Medical University, Hefei, China Institute of Reproductive Medicine, Anhui Medical University, Hefei, China Anhui Provincial Engineering Technology Research Center of Biopreservation and Artificial Organs, Hefei, China.
authors.forename: Xiao-Jin
authors.initials: XJ
authors.lastname: He
authors.affiliation: Reproductive Medicine Center, The First Affiliated Hospital of Anhui Medical University, Hefei, China Institute of Reproductive Medicine, Anhui Medical University, Hefei, China Anhui Provincial Engineering Technology Research Center of Biopreservation and Artificial Organs, Hefei, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Song
authors.affiliation: Department of Biology, Anhui Medical University, Hefei, China State Key Laboratory Incubation Base of Dermatology, Ministry of National Science and Technology, Anhui Medical University, Hefei, China weidongdu@hotmail.com.
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Du
authors.affiliation: Reproductive Medicine Center, The First Affiliated Hospital of Anhui Medical University, Hefei, China Institute of Reproductive Medicine, Anhui Medical University, Hefei, China Anhui Provincial Engineering Technology Research Center of Biopreservation and Artificial Organs, Hefei, China caoyunxia6@126.com.
authors.forename: Yun-Xia
authors.initials: YX
authors.lastname: Cao
authors.affiliation: Department of Biology, Anhui Medical University, Hefei, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Reproductive Medicine Center, Yijishan Hospital of Wannan Medical University, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Ruan
authors.affiliation: Department of Cell and Developmental Biology, School of Life Sciences, University of Science and Technology of China, Hefei, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Tian
authors.affiliation: State Key Laboratory Incubation Base of Dermatology, Ministry of National Science and Technology, Anhui Medical University, Hefei, China.
authors.forename: Fu-Sheng
authors.initials: FS
authors.lastname: Zhou
authors.affiliation: State Key Laboratory Incubation Base of Dermatology, Ministry of National Science and Technology, Anhui Medical University, Hefei, China.
authors.forename: Xian-Bo
authors.initials: XB
authors.lastname: Zuo
authors.affiliation: Reproductive Medicine Center, The First Affiliated Hospital of Anhui Medical University, Hefei, China Institute of Reproductive Medicine, Anhui Medical University, Hefei, China Anhui Provincial Engineering Technology Research Center of Biopreservation and Artificial Organs, Hefei, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Wu
authors.affiliation: Reproductive Medicine Center, The First Affiliated Hospital of Anhui Medical University, Hefei, China Institute of Reproductive Medicine, Anhui Medical University, Hefei, China Anhui Provincial Engineering Technology Research Center of Biopreservation and Artificial Organs, Hefei, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Zha
authors.affiliation: Department of Biology, Anhui Medical University, Hefei, China.
authors.forename: Xu-Shi
authors.initials: XS
authors.lastname: Xie
authors.affiliation: Reproductive Medicine Center, The First Affiliated Hospital of Anhui Medical University, Hefei, China Institute of Reproductive Medicine, Anhui Medical University, Hefei, China Anhui Provincial Engineering Technology Research Center of Biopreservation and Artificial Organs, Hefei, China.
authors.forename: Zhao-Lian
authors.initials: ZL
authors.lastname: Wei
authors.affiliation: Reproductive Medicine Center, The First Affiliated Hospital of Anhui Medical University, Hefei, China Institute of Reproductive Medicine, Anhui Medical University, Hefei, China Anhui Provincial Engineering Technology Research Center of Biopreservation and Artificial Organs, Hefei, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhou
mesh_terms: D000328:Adult; D044466:Asian People; D053713:Azoospermia / Q000235:genetics*; D016022:Case-Control Studies; D051786:Cyclic AMP Response Element Modulator / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D015398:Signal Transduction; D055815:Young Adult
chemical_list: C497410:CREM protein, human; D051786:Cyclic AMP Response Element Modulator
keywords: cyclic AMP-responsive element modulator (CREM); male infertility; nonobstructive azoospermia; single nucleotide polymorphisms