RESUMO
OBJECTIVE: To study whether reported, but inconsistent, associations between the FMR1 CGG repeat lengths in the intermediate, high normal, or low normal range differentiate women diagnosed with diminished ovarian reserve (DOR) from population controls and whether associations vary by race/ethnic group. DESIGN: Case-control study. SETTING: Academic and private fertility clinics. PATIENT(S): DOR cases (n = 129; 95 Whites, 22 Asian, 12 other) from five U.S. fertility clinics were clinically diagnosed, with regular menses and no fragile X syndrome family history. Normal fertility controls (n = 803; 386 Whites, 219 African-Americans, 102 Japanese, 96 Chinese) from the United States-based SWAN Study had one or more menstrual period in the 3 months pre-enrollment, one or more pregnancy, no history of infertility or hormone therapy, and menopause ≥46 years. Previously, the SWAN Chinese and Japanese groups had similar FMR1 CGG repeat lengths, thus they were combined. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): FMR1 CGG repeat lengths. RESULT(S): Median CGG repeats were nearly identical by case/control group. DOR cases had fewer CGG repeats in the shorter FMR1 allele than controls among Whites, but this was not significant among Asians. White cases had fewer CGG repeats in the shorter allele than Asian cases. No significant differences were found in the high normal/intermediate range between cases and controls or by race/ethnic group within cases in the longer allele. CONCLUSION(S): This study refutes prior reports of an association between DOR and high normal/intermediate repeats and confirms an association between DOR and low normal repeats in Whites.
Assuntos
Asiático/genética , Negro ou Afro-Americano/genética , Proteína do X Frágil da Deficiência Intelectual/genética , Hispânico ou Latino/genética , Infertilidade Feminina/etnologia , Infertilidade Feminina/genética , Reserva Ovariana/genética , População Branca/genética , Adulto , Estudos de Casos e Controles , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Infertilidade Feminina/diagnóstico , Infertilidade Feminina/fisiopatologia , Pessoa de Meia-Idade , Fenótipo , Fatores de Risco , Repetições de Trinucleotídeos , Estados Unidos/epidemiologiaRESUMO
FMR1 premutation carriers (55-199 CGG repeats), and potentially women with high normal (35-44) or low normal (<28) CGG repeats, are at risk of premature ovarian aging. The scarcity of population data on CGG repeats <45 CGG, and variation in race-ethnicity, makes it difficult to determine true associations. DNA was analyzed for FMR1 CGG repeat lengths from 803 women (386 caucasians, 219 African Americans, 102 Japanese, and 96 Chinese) from the US-based Study of Women's Health Across the Nation (SWAN). Participants had ≥1 menses in the 3 months before enrollment, ≥1 pregnancy, no history of infertility or hormonal therapy, and menopause ≥46 years. Statistical analyses used Fisher exact tests. Among these women with normal reproductive histories, significant FMR1 repeat length differences were found across race-ethnicity for both the longer (P = .0002) and the shorter (P < .0001) alleles. The trinucleotide length variance was greater for non-Asian than Asian women (P < .0001), despite identical median values. Our data indicate that short allele lengths <25 CGG on one or both alleles are more common in non-Asian than Asian women. We confirm the minor allele in the 35 to 39 CGG range among Asians as reported previously. Only 2 (0.3%) premutation carriers were identified. These data demonstrate that FMR1 distributions do vary by race-ethnicity, even within the "normal" range. This study indicates the need to control for race-ethnicity in FMR1 ovarian aging research and provides race-ethnic population data for females separated by allele.
Assuntos
Asiático/genética , Negro ou Afro-Americano/genética , Proteína do X Frágil da Deficiência Intelectual/genética , População Branca/genética , Adulto , Estudos de Coortes , Feminino , Fertilidade/genética , Predisposição Genética para Doença , Humanos , Pessoa de Meia-Idade , Valores de Referência , Repetições de Trinucleotídeos , Estados Unidos , Saúde da Mulher/etnologiaRESUMO
We aimed to evaluate the effect of a Japanese herbal medicine, Hochu-ekki-to (TJ-41), on daily activity in a murine model of chronic fatigue syndrome (CFS). CFS was induced by repeated injection of Brucella abortus (BA) antigen every 2 weeks. TJ-41 was orally administered to mice in a dose of 500 mg/kg/day for 1 week before injecting BA and for 4 weeks thereafter. We evaluated daily running activity in mice receiving TJ-41 as compared with that in untreated mice. Survival of both mouse groups was also monitored during the observation period. Body weight (BW), spleen weight (SW), SW/ BW ratio and expression levels of interleukin-10 (IL-10) mRNA in spleen were determined in both groups at the time of sacrifice. The daily activity was significantly higher in the treated group than in the control. Two mice in the untreated group died 2 days after the second injection of BA, whereas no mice in the group treated with TJ-41 died. The SW and SW/BW ratio were significantly lower in the treated mice than in the control. Suppressed IL-10 mRNA levels were observed in the spleens of the mice treated with TJ-41. Our data suggest that Hochu-ekki-to might possess an inhibitory effect on the marked decrease in running activity following BA injection.