Distribution of the FMR1 gene in females by race/ethnicity: women with diminished ovarian reserve versus women with normal fertility (SWAN study).
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.



Case-control study.



Academic and private fertility clinics.



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.



None.



FMR1 CGG repeat lengths.



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.



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.
OB/GYN and Reproductive Medicine Department, Stony Brook Medicine, Stony Brook, New York. Electronic address: pastorestudies@gmail.com.
Lisa M
LM
Pastore
UNC Fertility, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Steven L
SL
Young
Center for Public Health Genomics, Division of Biostatistics and Epidemiology, University of Virginia, Charlottesville, Virginia; Department of Public Health Sciences, Division of Biostatistics and Epidemiology, University of Virginia, Charlottesville, Virginia.
Ani
A
Manichaikul
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Stanford University, Stanford, California.
Valerie L
VL
Baker
Department of Public Health Sciences, Division of Biostatistics and Epidemiology, University of Virginia, Charlottesville, Virginia.
Xin Q
XQ
Wang
Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts.
Joel S
JS
Finkelstein
D000328:Adult; D001741:Black or African American / Q000235:genetics*; D001213:Asian / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006630:Hispanic or Latino / Q000235:genetics*; D006801:Humans; D007247:Infertility, Female / Q000175:diagnosis / Q000208:ethnology* / Q000235:genetics* / Q000503:physiopathology; D008875:Middle Aged; D065851:Ovarian Reserve / Q000235:genetics*; D010641:Phenotype; D012307:Risk Factors; D018911:Trinucleotide Repeats; D014481:United States / Q000453:epidemiology; D044465:White People / Q000235:genetics*
D051860:Fragile X Messenger Ribonucleoprotein 1; C497683:FMR1 protein, human
Asian Continental Ancestry Group; Diminished ovarian reserve; European Continental Ancestry Group; FMR1; female; infertility; ovarian reserve; race/ethnicity