Associations between polymorphisms in glucuronidation and sulfation enzymes and sex steroid concentrations in premenopausal women in the United States.
Associations between polymorphisms in glucuronidation and sulfation enzymes and sex steroid concentrations in premenopausal women in the United States.
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美国绝经前女性葡萄糖醛酸化酶和硫酸化酶的多态性与性类固醇浓度之间的关联。
DOI：
10.1016/j.jsbmb.2010.12.014
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Lampe,JohannaW
中科院分区：
文献类型：
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作者：
Yong,Mellissa;Schwartz,StephenM;Atkinson,Charlotte;Makar,KarenW;Thomas,SushmaS;Stanczyk,FrankZ;Westerlind,KimC;Newton,KatherineM;Holt,VictoriaL;Leisenring,WendyM;Lampe,JohannaW
由UDP-葡萄糖醛酸转移酶（UGT）催化的葡萄糖醛酸化和由磺基转移酶（SULT）催化的硫酸化是性类固醇代谢为活性较低化合物的途径。这些酶是高度多态性的，并且遗传变体经常导致更高或更低的活性。这些多态性对绝经前妇女循环性类固醇的表型影响尚未研究。170名年龄在40-45岁的女性在月经周期的卵泡期抽取血液样本进行性类固醇测量并获得基因组DNA。收集尿液用于2-羟基（OH）雌酮（E1）和16α-OH E1测定。广义线性回归模型用于评估性类固醇与UGT 1A和UGT 2B家族、SULT 1A 1和SULT 1 E1多态性之间的关联。与野生型（TA 6/TA 6）相比，具有UGT 1A 1（TA 7/TA 7）基因型的女性平均雌二醇（E2）浓度低25%（p=0.02）。在SULT 1A 1（R213/H213）和E1（与野生型相比，平均E1浓度降低13%; p值=0.02）以及UGT 2B 4（E458/E458）和脱氢表雄酮（DHEA）（与野生型相比，平均DHEA降低20%; p值=0.03）之间观察到类似的相关性。SULT 1 E1（A/C）和UGT 1A 1（TA 7）-UGT 1A 3（R11）单倍型与雌激素浓度降低相关。在更大的绝经前妇女人群中进一步研究UGT和SULT多态性和循环性类固醇激素的测量是必要的。
Glucuronidation, catalyzed by UDP-glucuronosyltransferases (UGT) and sulfation, catalyzed by sulfotransferases (SULT), are pathways through which sex steroids are metabolized to less active compounds. These enzymes are highly polymorphic and genetic variants frequently result in higher or lower activity. The phenotypic effects of these polymorphisms on circulating sex steroids in premenopausal women have not yet been investigated. One hundred and seventy women aged 40–45 years had a blood sample drawn during the follicular phase of the menstrual cycle for sex steroid measures and to obtain genomic DNA. Urine was collected for 2-hydroxy (OH) estrone (E1) and 16α-OH E1measures. Generalized linear regression models were used to assess associations between sex steroids and polymorphisms in the UGT1A and UGT2B families, SULT1A1, and SULT1E1. Women with the UGT1A1(TA7/TA7) genotype had 25% lower mean estradiol (E2) concentrations compared to the wildtype (TA6/TA6) (p=0.02). Similar associations were observed between SULT1A1(R213/H213) and E1(13% lower mean E1concentration vs. wildtype; p-value=0.02) and UGT2B4(E458/E458) and dehydroepiandrosterone (DHEA) (20% lower mean DHEA vs. wildtype; p-value=0.03). The SULT1E1(A/C) and the UGT1A1(TA7)–UGT1A3(R11) haplotypes were associated with reduced estrogen concentrations. Further study of UGT and SULT polymorphisms and circulating sex steroid measures in larger populations of premenopausal women is warranted.