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J Androl. 2012 Jul-Aug;33(4):675-83. doi: 10.2164/jandrol.111.013995. Epub 2011 Oct 20.

Association study of single-nucleotide polymorphisms in FASLG, JMJDIA, LOC203413, TEX15, BRDT, OR2W3, INSR, and TAS2R38 genes with male infertility.

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  • 1Research Center for Genetic Engineering and Biotechnology, Macedonian Academy of Sciences and Arts, Av Krste Misirkov 2, POB 428, 1000 Skopje, Republic of Macedonia.

Abstract

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%]).

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