Plaseski Toso, Noveski Predrag, Popeska Zaneta, Efremov Georgi D, Plaseska-Karanfilska Dijana
Research Center for Genetic Engineering and Biotechnology, Macedonian Academy of Sciences and Arts, Av Krste Misirkov 2, POB 428, 1000 Skopje, Republic of Macedonia.
J Androl. 2012 Jul-Aug;33(4):675-83. doi: 10.2164/jandrol.111.013995. Epub 2011 Oct 20.
Infertility is a major health problem today, affecting about 15% of couples trying to conceive a child. Impaired fertility of the male factor is causative in 20% of infertile couples and contributory in up to another 30%-40%. Based on association studies, an increasing number of gene polymorphisms have been proposed to modulate the efficiency of spermatogenesis. Here, we have investigated the possible association of 9 single-nucleotide polymorphisms (SNP) in 8 different genes-FASLG, JMJDIA, LOC203413, TEX15, BRDT, OR2W3, INSR, and TAS2R38--with male infertility. We analyzed a total of 136 men with idiopathic infertility (60 azoospermic and 76 oligozoospermic) and 161 fertile controls. Our study group included individuals of different ethnic origin: 93 of the infertile men were Macedonians, 32 were Albanians, and 11 were of other origin. The control group was composed of 125 Macedonian and 36 Albanian men. The methodology included multiplex polymerase chain reaction/SNaPshot analyses, followed by capillary electrophoresis on an ABI3130 Genetic Analyzer. Of the 9 SNPs evaluated, 3 are significantly associated (P < .05) with male infertility: SNPs rs5911500 in LOC203413, rs3088232 in BRDT, and rs11204546 in OR2W3. SNP rs5911500 showed the strongest association with infertility among Albanians (P = .0001), whereas rs3088232 was most significantly associated with azoospermia among Macedonians (P = .0082). Moreover, the frequency of co-occurrence of LOC203413 minor T allele with either homozygosity or heterozygosity for the BRDT minor G allele was significantly higher among both azoospermic (6 of 60 [10%]; P = .0057; odds ratio [95% confidence interval], 8.83 [1.73-45.08]) and oligozoospermic (10 of 76 [13.2%]; P = .0002; odds ratio [95% confidence interval], 12.04 [2.57-56.47]) men in comparison with fertile controls (2 of 161 [1.2%]).
不孕不育是当今一个主要的健康问题，影响着约15%试图受孕的夫妇。男性因素导致的生育能力受损在20%的不孕夫妇中起作用，另外在高达30%-40%的夫妇中起促成作用。基于关联研究，越来越多的基因多态性被认为可调节精子发生的效率。在此，我们研究了8个不同基因（FASLG、JMJDIA、LOC203413、TEX15、BRDT、OR2W3、INSR和TAS2R38）中的9个单核苷酸多态性（SNP）与男性不育的可能关联。我们共分析了136名特发性不育男性（60名无精子症患者和76名少精子症患者）以及161名生育力正常的对照者。我们的研究组包括不同种族的个体：93名不育男性为马其顿人，32名是阿尔巴尼亚人，11名来自其他种族。对照组由125名马其顿男性和36名阿尔巴尼亚男性组成。方法包括多重聚合酶链反应/SNaPshot分析，随后在ABI3130基因分析仪上进行毛细管电泳。在评估的9个SNP中，有3个与男性不育显著相关（P < 0.05）：LOC203413中的SNP rs5911500、BRDT中的rs3088232以及OR2W3中的rs11204546。SNP rs5911500在阿尔巴尼亚人中与不育的关联最强（P = 0.0001），而rs3088232在马其顿人中与无精子症的关联最为显著（P = 0.0082）。此外，在无精子症患者（60例中有6例[10%]；P = 0.0057；优势比[95%置信区间]，8.83[1.73 - 45.08]）和少精子症患者（76例中有10例[13.2%]；P = 0.0002；优势比[95%置信区间]，12.04[2.57 - 56.47]）中，LOC203413的次要T等位基因与BRDT次要G等位基因的纯合或杂合同时出现的频率显著高于生育力正常的对照者（161例中有2例[1.2%]）。
