目的:评估参与雄激素受体(AR)信号传导的基因作为多囊卵巢综合征(PCOS)的候选基因。
方法:两组PCOS妇女和对照妇女(发现和复制队列),对AR伴侣和共伴侣的八个基因中的单核苷酸多态性(SNP)进行了基因分型:HSPA1A,HSPA8、ST13、STIP1、PTGES3、FKBP4、BAG1和STUB1。测试了单核苷酸多态性与PCOS状态以及与雄激素和代谢参数的关联。
方法:三级转诊中心。
方法:发现队列:354名PCOS患者和161名对照女性。复制队列:397名PCOS女性和306名对照女性。
方法:表型和基因型评估。
方法:单核苷酸多态性基因型,与PCOS状态相关,以及雄激素和代谢参数。
结果:在发现队列中,FKBP4SNPrs2968909和rs4409904与较低的PCOS几率相关。这一发现在复制队列分析中没有得到证实;然而,当将这两个队列组合在一起时,rs4409904与较低的PCOS几率相关。在复制队列以及合并队列中患有PCOS的受试者中,rs2968909与较低的体重指数相关。
结论:编码AR共同伴侣FKBP52的FKBP4的单核苷酸多态性可能与PCOS患者的PCOS和体重指数相关。研究的其余基因似乎不是PCOS发展的主要贡献者。这些发现值得在未来的研究中得到证实,和编码其他雄激素途径组分的基因仍有待研究。
OBJECTIVE: To evaluate genes involved in androgen receptor (AR) signaling as candidate genes for polycystic ovary syndrome (PCOS).
METHODS: Two groups of women with PCOS and control women (discovery and replication cohorts), were genotyped for single-nucleotide polymorphisms (SNPs) in eight genes for AR
chaperones and co-
chaperones: HSPA1A, HSPA8, ST13, STIP1, PTGES3, FKBP4, BAG1, and STUB1. Single-nucleotide polymorphisms were tested for association with PCOS status and with androgenic and metabolic parameters.
METHODS: Tertiary referral center.
METHODS: Discovery cohort: 354 women with PCOS and 161 control women. Replication cohort: 397 women with PCOS and 306 control women.
METHODS: Phenotypic and genotypic assessment.
METHODS: Single-nucleotide polymorphism genotypes, association with PCOS status, and androgenic and metabolic parameters.
RESULTS: In the discovery cohort, FKBP4 SNPs rs2968909 and rs4409904 were associated with lower odds of PCOS. This finding was not confirmed in the replication cohort analysis; however, when combining the two cohorts, rs4409904 was associated with lower odds of PCOS. In subjects with PCOS in the replication cohort as well as in the combined cohort, rs2968909 was associated with lower body mass index.
CONCLUSIONS: Single-nucleotide polymorphisms in FKBP4, which codes for the AR co-chaperone FKBP52, may be associated with PCOS and body mass index in patients with PCOS. The remaining genes studied do not seem to be major contributors to the development of PCOS. These findings warrant confirmation in future studies, and genes encoding other androgen pathway components remain to be studied.