• PMID: 20610805
• Gene Name: BCL2
• Condition: Azoospermia
• Association: In addition, HeLa cells expressing the BCL2 Ala43Thr (G127A), similar to the control cells, were more sensitive to paclitaxel-induced cytotoxicity and apoptosis than those expressing wild-type BCL2.
• PMID: 20610805
• Gene Name: BCL2
• Condition: Azoospermia
• Association: Consistently, the cleaved PARP and p-BCL2 proteins were subsequently increased after paclitaxel treatment, as also predicted by the bioinformatics analysis. Considering the decreased antiapoptotic function of BCL2, these results suggest that the Ala43Thr
• Mutation: Ala43Thr
• Population size: 381
• Population details: 381 (198 infertile patients with idiopathic azoospermia, 183 fertile controls)
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Azoospermia

BCL2 Ala43Thr is a functional variant associated with protection against azoospermia in a Han-Chinese population

Ma J, Lu HY, Xia YK, Dong HB, Gu AH, Li ZY, Li Z, Chen AM, Wang XR, Wang SL.

Apoptosis is very common during various stages of mammalian germ cell development and differentiation, and the BCL2 gene is one of the most important apoptotic regulators. Although its genetic variants are reported to be involved in cancers and autoimmune diseases, little information is available regarding BCL2 polymorphisms in male spermatogenesis. In the present study, single nucleotide polymorphisms (SNPs) in coding regions of the BCL2 gene were examined in a hospital-based, case-control study including 198 infertile patients with idiopathic azoospermia and 183 fertile controls. Subsequently, a functional study was conducted for comparison of paclitaxel-induced cytotoxicity and apoptosis between the BCL2 variant and the wild type in vitro. Three SNPs were found in exon 2--A21G (rs1801018), G127A (rs1800477), and C300T (rs61733416)--with the latter first reported in the Han-Chinese population. The frequency of G127A (GA+AA) genotype was significantly lower in azoospermic, infertile men compared to the age-matched controls (P = 0.01). This genotype may confer a lower risk of azoospermia (adjusted odd ratio [OR] = 0.448, 95% confidence interval = 0.226-0.889). In addition, HeLa cells expressing the BCL2 Ala43Thr (G127A), similar to the control cells, were more sensitive to paclitaxel-induced cytotoxicity and apoptosis than those expressing wild-type BCL2. Consistently, the cleaved PARP and p-BCL2 proteins were subsequently increased after paclitaxel treatment, as also predicted by the bioinformatics analysis. Considering the decreased antiapoptotic function of BCL2, these results suggest that the Ala43Thr variant is associated with protection against azoospermia in the Han-Chinese population. FAU - Ma, Jun AU - Ma J AD - Key Lab of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing, People's Republic of China. FAU - Lu, Hui-Yuan AU - Lu HY FAU - Xia, Yan-Kai AU - Xia YK FAU - Dong, Hui-Bin AU - Dong HB FAU - Gu, Ai-Hua AU - Gu AH FAU - Li, Zi-Yin AU - Li ZY FAU - Li, Zhong AU - Li Z FAU - Chen, Ai-Min AU - Chen AM FAU - Wang, Xin-Ru AU - Wang XR