FSHB promoter polymorphism within evolutionary conserved element is associated with serum FSH level in men.
FSHB promoter polymorphism within evolutionary conserved element is associated with serum FSH level in men.
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DOI：
10.1093/humrep/den216
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发表时间：
2008-09
期刊：
影响因子：
--
通讯作者：
Laan M
中科院分区：
文献类型：
--
作者：
Grigorova M;Punab M;Ausmees K;Laan M
在人类FSHB基因中没有描述影响血清FSH水平的多态性。我们在胎盘哺乳动物FSHB mRNA转录起始位点上游211 bp处发现了一个潜在的调控单核苷酸多态性（SNP, rs10835638; G/T），位于一个高度保守的区域。我们的目的是确定rs10835638替代等位基因的携带者状态与男性血清FSH水平、睾丸和激素参数的相关性。对爱沙尼亚塔尔图大学医院男科中心就诊的健康男性（n = 554，年龄19.2±1.7岁）进行定量遗传关联研究。Rs10835638（等位基因频率：G 87.6%, T 12.4%）与血清FSH水平显著相关（方差分析：F = 13.0, P = 0.0016, df = 1；回归检验呈线性趋势：P = 0.0003）。GG基因型受试者FSH水平（3.37±1.79 IU/l, n = 423）高于杂合子组（2.84±1.54 IU/l, n = 125） （P = 0.0005）、t等位基因携带者组（GT+TT, 2.78±1.51 IU/l, n = 131） （P = 0.0005）和TT纯合子组（2.02±0.81 IU/l, n = 6） （P = 0.031）。Rs10835638与游离睾酮指数和睾丸体积显著（P < 0.05）降低相关，而与精液体积、性激素结合球蛋白、血清睾酮和雌二醇升高相关。两组间LH和抑制素b水平无显著差异。FSHB启动子中调控SNP的鉴定为研究结构性低FSH对男性健康和生育能力的影响铺平了道路。由于FSH有助于女性卵泡发育和性类固醇的产生，这种FSHB变异在女性生殖成功中的作用仍有待研究。
No polymorphisms affecting serum FSH levels have been described in the human FSHB gene. We have identified a potential regulatory single nucleotide polymorphism (SNP, rs10835638; G/T) 211 bp upstream from the FSHB mRNA transcription start-site, located within a highly conserved region among placental mammals. We aimed to determine the correlation of carrier status of rs10835638 alternative alleles with serum FSH level in men, and testicular and hormonal parameters. A quantitative genetic association study using a cohort of healthy men (n = 554; age 19.2 ± 1.7 years) visiting the Centre of Andrology, Tartu University Hospital, Estonia. Rs10835638 (allele frequencies: G 87.6%, T 12.4%) was significantly associated with serum FSH level (analysis of variance: F = 13.0, P = 0.0016, df = 1; regression testing for a linear trend: P = 0.0003). Subjects with the GG genotype exhibited higher FSH levels (3.37 ± 1.79 IU/l, n = 423) compared with heterozygotes (2.84 ± 1.54 IU/l, n = 125) (P = 0.0005), the group of T-allele carriers (GT+TT, 2.78 ± 1.51 IU/l, n = 131) (P = 0.0005) and TT-homozygotes (2.02 ± 0.81 IU/L, n = 6) (P = 0.031). Rs10835638 was also associated with significant (P < 0.05) reduction in free testosterone index and testes volume, but increased semen volume, sex hormone-binding globulin, serum testosterone and estradiol. LH and inhibin-B levels did not differ significantly between groups. The identification of a regulatory SNP in FSHB promoter paves the way to study the effect of constitutively low FSH on male health and fertility. As FSH contributes to follicular development and sex steroid production in women, the role of this FSHB variant in female reproductive success is still to be addressed.
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