Weiqiang Zhu1,2, Jing Du2, Qing Chen1, Zhaofeng Zhang2, Bin Wu2, Jianhua Xu2, Tianqi Li2, Yuan Bi2, Huijuan Shi3, Runsheng Li4. 1. NHC Key Laboratory of Birth Defects and Reproductive Health, Chongqing Population and Family Planning Science and Technology Research Institute, Chongqing, China. 2. NHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Pharmacy School, Fudan University, 2140 Xietu Road, Shanghai, 200032, China. 3. NHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Pharmacy School, Fudan University, 2140 Xietu Road, Shanghai, 200032, China. shihuijuan2011@163.com. 4. NHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Pharmacy School, Fudan University, 2140 Xietu Road, Shanghai, 200032, China. runshengli2007@163.com.
Abstract
BACKGROUND: UHRF1 plays an important role in maintaining DNA methylation patterns during spermatogenesis. This study was performed to evaluate the association between UHRF1 gene variations and infertility in males with oligozoospermia in a Chinese population. METHODS: In this case-control study of 735 Chinese men, single-nucleotide polymorphism (SNP) genotypes and alleles in the UHRF1 gene were assessed by direct sequencing. The effects of the mutations on UHRF1 transcription were investigated using a dual-luciferase reporter gene assay. RESULTS: We identified 24 SNPs, including nine SNPs in the promoter region, three in the 5' untranslated region, five in introns, and seven in exons. Interestingly, the genotype frequencies of SNP rs2656927 (P = 0.014) and rs8103849 (P < 0.001) significantly differed between men with oligozoospermia in case group 1 and normozoospermic men. Moreover, four variants (three were novel) were detected only in the patient group, with two in introns and the others in the promoter region. The results of the luciferase assay showed that the -1615C>T-C and -1562A>G-A alleles increased luciferase activity compared with the -1615C>T-T and -1562A>G-G alleles. CONCLUSIONS: We detected two SNPs in the UHRF1 gene showing a significant difference between the case and control groups. Two screened SNPs affected UHRF1 promoter activity, improving the understanding of the pathophysiology of oligozoospermia.
BACKGROUND:UHRF1 plays an important role in maintaining DNA methylation patterns during spermatogenesis. This study was performed to evaluate the association between UHRF1 gene variations and infertility in males with oligozoospermia in a Chinese population. METHODS: In this case-control study of 735 Chinese men, single-nucleotide polymorphism (SNP) genotypes and alleles in the UHRF1 gene were assessed by direct sequencing. The effects of the mutations on UHRF1 transcription were investigated using a dual-luciferase reporter gene assay. RESULTS: We identified 24 SNPs, including nine SNPs in the promoter region, three in the 5' untranslated region, five in introns, and seven in exons. Interestingly, the genotype frequencies of SNP rs2656927 (P = 0.014) and rs8103849 (P < 0.001) significantly differed between men with oligozoospermia in case group 1 and normozoospermic men. Moreover, four variants (three were novel) were detected only in the patient group, with two in introns and the others in the promoter region. The results of the luciferase assay showed that the -1615C>T-C and -1562A>G-A alleles increased luciferase activity compared with the -1615C>T-T and -1562A>G-G alleles. CONCLUSIONS: We detected two SNPs in the UHRF1 gene showing a significant difference between the case and control groups. Two screened SNPs affected UHRF1 promoter activity, improving the understanding of the pathophysiology of oligozoospermia.
Authors: Gianfranco Carlomagno; Maaike P A van Bragt; Cindy M Korver; Sjoerd Repping; Dirk G de Rooij; Ans M M van Pelt Journal: Biol Reprod Date: 2010-07-21 Impact factor: 4.285
Authors: A Fujimori; Y Matsuda; Y Takemoto; Y Hashimoto; E Kubo; R Araki; R Fukumura; K Mita; K Tatsumi; M Muto Journal: Mamm Genome Date: 1998-12 Impact factor: 2.957