Department of Biology, University of Pisa, Via Luca Ghini, 13, Pisa 56126, Italy.
Department of Molecular and Developmental Medicine, University of Siena, Viale Bracci 16, Siena 53100, Italy.
Hum Reprod. 2017 Nov 1;32(11):2324-2331. doi: 10.1093/humrep/dex305.
Are polymorphisms of taste receptor genes associated with male infertility?
This study has showed the associations between three single nucleotide polymorphisms (SNPs) in taste receptors genes (TASR) and male infertility.
Recent studies showed the expression of taste receptors in the testis and in spermatozoa, suggesting their possible role in infertility. The vast genetic variability in taste genes results in a large degree of diversity in various human phenotypes.
STUDY DESIGN, SIZE, DURATION: In this study, we genotyped 19 SNPs in 12 taste related genes in a total of 494 Caucasian male patients undergoing semen evaluation at the Centre of Couple Sterility of the Siena University Hospital. Consecutive patients were enrolled during infertility investigations from October 2014 to February 2016.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Median age of the patients was 36 years (18-58) and 141 were smokers. Genotyping was performed using the allele-specific PCR. The statistical analysis was carried out using generalized linear model (GLM) to explore the association between age, smoking, the genetic polymorphisms and sperm parameters.
We observed that the homozygous carriers of the (G) allele of the TAS2R14-rs3741843 polymorphism showed a decreased sperm progressive motility compared to heterozygotes and (A) homozygotes (P = 0.003). Moreover, the homozygous carriers of the (T) allele of the TAS2R3-rs11763979 SNP showed fewer normal acrosome compared with the heterozygous and the homozygous carriers of the (G) allele (P = 0.002). Multiple comparisons correction was applied and the Bonferroni-corrected critical P-value was = 0.003.
LIMITATIONS, REASONS FOR CAUTION: The analysis is restricted to SNPs within genes and to men of Caucasian ancestry.
In silico analyses strongly point towards a functional effect of the two SNPs: TAS2R14-rs3741843 regulates TAS2R43 expression, a gene that is involved in cilia motility and therefore could influences sperm mobility; the (T) allele of TAS2R3-rs11763979 increases the expression of the WEE2 antisense RNA one gene (WEE2-AS1). According to Genotype-Tissue Expression (GTEx) project the WEE2 gene is expressed in the testes where presumably it has the role of down regulating meiotic cell division. It is plausible to hypothesize that the WEE2-AS1 increased expression may down regulate WEE2 which in turn can alter the natural timing of sperm maturation increasing the number of abnormal sperm cells.
STUDY FUNDING/COMPETING INTEREST(S): None.
味觉受体基因多态性与男性不育有关吗？
本研究表明味觉受体基因（TASR）中的三个单核苷酸多态性（SNP）与男性不育之间存在关联。
最近的研究表明，味觉受体在睾丸和精子中表达，表明它们可能在不育症中发挥作用。味觉基因的巨大遗传多样性导致了人类各种表型的高度多样性。
研究设计、大小和持续时间：在这项研究中，我们在 12 个味觉相关基因中的 19 个 SNP 中对总共 494 名接受锡耶纳大学医院夫妇不育中心精液评估的白种人男性患者进行了基因分型。连续患者于 2014 年 10 月至 2016 年 2 月期间在不孕调查中招募。
参与者/材料、地点、方法：患者的中位年龄为 36 岁（18-58 岁），141 人吸烟。使用等位基因特异性 PCR 进行基因分型。使用广义线性模型（GLM）进行统计分析，以探讨年龄、吸烟、遗传多态性与精子参数之间的关系。
我们观察到 TAS2R14-rs3741843 多态性的（G）等位基因纯合子携带者的精子前向运动能力比杂合子和（A）纯合子携带者降低（P=0.003）。此外，TAS2R3-rs11763979 中 TAS2R3 单核苷酸多态性的（T）等位基因纯合子携带者的正常顶体数比杂合子和（G）等位基因纯合子携带者少（P=0.002）。应用多重比较校正，Bonferroni 校正的临界 P 值为=0.003。
局限性、谨慎的原因：分析仅限于基因内的 SNP 和高加索血统的男性。
计算机分析强烈指向两个 SNP 的功能作用：TAS2R14-rs3741843 调节 TAS2R43 的表达，该基因参与纤毛运动，因此可能影响精子的运动能力；TAS2R3-rs11763979 的（T）等位基因增加了 WEE2 反义 RNA 一个基因（WEE2-AS1）的表达。根据基因型组织表达（GTEx）项目，WEE2 基因在睾丸中表达，据推测它在下调减数分裂细胞分裂中起作用。可以合理假设，WEE2-AS1 表达的增加可能下调 WEE2，从而改变精子成熟的自然时间，增加异常精子细胞的数量。
研究资金/利益冲突：无。
