Fertility and sterility · 2006
Ethnic distribution of estrogen receptor-alpha polymorphism is associated with a higher prevalence of uterine leiomyomas in black Americans.
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Al-Hendy Ayman, Salama Salama A
Аннотация
OBJECTIVE: To investigate whether polymorphisms in the estrogen receptor alpha (ERalpha) gene are associated with an increased risk of uterine leiomyomas (ULMs).
DESIGN: Genomic DNA was isolated from normal myometrium samples collected at the time of the hysterectomy.
SETTING: Volunteers in an academic research environment.
PATIENT(S): One hundred ninety-eight women with surgically confirmed ULMs and 229 matched controls with nonfibroid uteri.
INTERVENTION(S): Hysterectomy samples were collected from volunteers.
MAIN OUTCOME MEASURE(S): The two PvuII and XbaI intronic polymorphisms in the ERalpha gene using polymerase chain reaction and restriction fragment length polymorphism.
RESULT(S): The ERalpha PP genotype was associated with a significantly increased risk of ULM in black and white women, but not in Hispanic women. Women with the ERalpha PP genotype were 6.42 times (confidence limits 2.04-20.16) more likely to have ULMs than other genotypes. The ERalpha PP genotype was also significantly associated with larger tumor burden (>400 g). The overall prevalence of the PP genotype was significantly higher in black women (35%) than white (13%) or Hispanic (16%) women. Myometrial cell lines expressing the PP genotype exhibited enhanced proliferative response to estrogen in vitro compared with their pp counterparts.
CONCLUSION(S): The ERalpha PP genotype is a genetic risk factor for ULM development among surgically treated women. The higher prevalence of this genotype in blacks might explain the increased occurrence of this tumor among black women.
DESIGN: Genomic DNA was isolated from normal myometrium samples collected at the time of the hysterectomy.
SETTING: Volunteers in an academic research environment.
PATIENT(S): One hundred ninety-eight women with surgically confirmed ULMs and 229 matched controls with nonfibroid uteri.
INTERVENTION(S): Hysterectomy samples were collected from volunteers.
MAIN OUTCOME MEASURE(S): The two PvuII and XbaI intronic polymorphisms in the ERalpha gene using polymerase chain reaction and restriction fragment length polymorphism.
RESULT(S): The ERalpha PP genotype was associated with a significantly increased risk of ULM in black and white women, but not in Hispanic women. Women with the ERalpha PP genotype were 6.42 times (confidence limits 2.04-20.16) more likely to have ULMs than other genotypes. The ERalpha PP genotype was also significantly associated with larger tumor burden (>400 g). The overall prevalence of the PP genotype was significantly higher in black women (35%) than white (13%) or Hispanic (16%) women. Myometrial cell lines expressing the PP genotype exhibited enhanced proliferative response to estrogen in vitro compared with their pp counterparts.
CONCLUSION(S): The ERalpha PP genotype is a genetic risk factor for ULM development among surgically treated women. The higher prevalence of this genotype in blacks might explain the increased occurrence of this tumor among black women.