Hypospadias and genes related to genital tubercle and early urethral development.
Hypospadias and genes related to genital tubercle and early urethral development.
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DOI：
10.1016/j.juro.2013.05.061
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发表时间：
2013-11
影响因子：
6.6
通讯作者：
Shaw, Gary M.
中科院分区：
文献类型：
--
作者：
Carmichael, Suzan L.;Ma, Chen;Choudhry, Shweta;Lammer, Edward J.;Witte, John S.;Shaw, Gary M.
我们确定了与生殖器结节（阴茎的原基）和早期尿道发育相关的基因变异是否与人类尿道下裂相关。我们检测了BMP 4、BMP 7、FGF 8、FGF 10、FGFR 2、HOXA 13、HOXD 13、HOXA 4、HOXB 6、SRY、WT 1、WTAP、SHH、GLI 1、GLI 2和GLI 3中293个相对常见的tagSNP。该分析包括624例病例（81例轻度，319例中度，209例重度，15例严重程度未定）和844例基于人群的非畸形男性对照，出生于1990-2003年的加州。有28个SNP的任何比较（即，总体或特定严重性）的p值<0.01。BMP 7中4个SNP的纯合变异基因型与尿道下裂风险增加至少2倍相关，无论严重程度如何。FGF 10的5个SNP与3- 4倍的风险增加相关，无论严重程度如何;其中4个SNP的结果仅限于白人。对于GLI 1，GLI 2和GLI 3，有12个相关的SNP，但结果在严重程度和种族之间不一致。对于SHH，一个SNP与中度尿道下裂风险增加2.4倍相关。对于WT 1，6个SNP与大约2倍的风险增加相关，主要是严重尿道下裂。这项研究提供的证据表明，在几个基因的单核苷酸多态性，有助于生殖器结节和早期尿道发育与尿道下裂的风险。
We determined whether variants in genes associated with genital tubercle (the anlage for the penis) and early urethral development were associated with hypospadias in humans. We examined 293 relatively common tagSNPs in BMP4, BMP7, FGF8, FGF10, FGFR2, HOXA13, HOXD13, HOXA4, HOXB6, SRY, WT1, WTAP, SHH, GLI1, GLI2, and GLI3. The analysis included 624 cases (81 mild, 319 moderate, 209 severe, 15 undetermined severity) and 844 population-based non-malformed male controls born in California from 1990-2003. There were 28 SNPs for which any of the comparisons (i.e., overall or for a specific severity) had a p-value <0.01. The homozygous variant genotypes for four SNPs in BMP7 were associated with at least 2-fold increased risk of hypospadias, regardless of severity. Five SNPs for FGF10 were associated with 3- to 4-fold increased risks, regardless of severity; for four of them, results were restricted to whites. For GLI1, GLI2 and GLI3, there were 12 associated SNPs but results were inconsistent by severity and race-ethnicity. For SHH, one SNP was associated with 2.4-fold increased risk of moderate hypospadias. For WT1, six SNPs were associated with approximately 2-fold increased risks, primarily for severe hypospadias. This study provides evidence that SNPs in several genes that contribute to genital tubercle and early urethral development are associated with hypospadias risk.
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