• PMID: 23630330
• Gene Name: RAG1
• Condition: Male infertility
• Association: In addition, the homozygous variant genotype GG of RAG1 rs2227973 (A>G, K820R) was associated with a significantly increased risk of male infertility (adjusted OR, 1.44; 95% CI, 1.01-2.04). Moreover, linear regression analysis revealed that carriers of LI
• PMID: 23630330
• Gene Name: RAG1
• Condition: Male infertility
• Association: This study demonstrates, for the first time, to our knowledge, that functional variants of RAG1 rs2227973 and LIG4 rs1805388 are associated with susceptibility to maleinfertility.
• Mutation: LIG4 rs1805388 (Ex2+54C>T, Thr9Ile), RAG1 rs2227973 (A>G, K820R)
• Population size: 1060
• Population details: 1060 (580 infertility cases, 580 controls)
• Sex: Male
• Infertility type: Male infertility
• Associated genes: RAG1, LIG4
• Other associated phenotypes: Male infertility

Polymorphisms in double-strand breaks repair genes are associated with impaired fertility in Chinese population

Ji G, Yan L, Liu W, Huang C, Gu A, Wang X.

The DNA double-strand breaks (DSBs) repair pathway plays a critical role in repairing double-strand breaks, and genetic variants in DSBs repair pathway genes are potential risk factors for various diseases. To test the hypothesis that polymorphisms in DSBs genes are associated with susceptibility to male infertility, we examined 11 single nucleotide polymorphisms in eight key DSBs genes (XRCC3, XRCC2, BRCA2, RAG1, XRCC5, LIG4, XRCC4 and ATM) in 580 infertility cases and 580 controls from a Chinese population-based case-control study (NJMU Infertility Study). Genotypes were determined using the OpenArray platform, and sperm DNA fragmentation was detected using the TUNEL assay. The adjusted odds ratio (OR) and 95% CI were estimated using logistic regression. The results indicate that LIG4 rs1805388 (Ex2+54C>T, Thr9Ile) T allele could increase the susceptibility to male infertility (adjusted OR=2.78; 95% CI, 1.77-4.36 for TT genotype; and adjusted OR=1.58; 95% CI, 1.77-4.36 for TC genotype respectively). In addition, the homozygous variant genotype GG of RAG1 rs2227973 (A>G, K820R) was associated with a significantly increased risk of male infertility (adjusted OR, 1.44; 95% CI, 1.01-2.04). Moreover, linear regression analysis revealed that carriers of LIG4 rs1805388 or RAG1 rs2227973 variants had a significantly higher level of sperm DNA fragmentation and that T allele carriers of LIG4 rs1805388 also had a lower level of sperm concentration when compared with common homozygous genotype carriers. This study demonstrates, for the first time, to our knowledge, that functional variants of RAG1 rs2227973 and LIG4 rs1805388 are associated with susceptibility to male infertility. FAU - Ji, Guixiang AU - Ji G AD - Nanjing Institute of Environmental Sciences/Key Laboratory of Pesticide Environmental Assessment and Pollution Control, Ministry of Environmental Protection, Nanjing 210042, People's Republic of China. FAU - Yan, Lifeng AU - Yan L FAU - Liu, Wei AU - Liu W FAU - Huang, Cong AU - Huang C FAU - Gu, Aihua AU - Gu A