DNA microarray-based analysis of single nucleotide polymorphisms may be useful for assessing the risks and benefits of hormone therapy.
OBJECTIVE
To determine what percentage of women can be given individualized counseling based on genetic information, as single nucleotide polymorphisms (SNPs) are associated with risks and benefits of estrogen therapy and hormone therapy such as thrombosis, myocardial infarction, breast cancer, and bone protection.


METHODS
Cross-sectional study.


METHODS
Academic research institution.


METHODS
A consecutive series of 2,507 perimenopausal and postmenopausal women.


METHODS
Peripheral venous puncture and multiplex polymerase chain reaction on a microarray system.


METHODS
Analysis of 22 SNPs of 17 genes: AGTMet235Thr, APOECys112Arg, APOEArg158Cys, COMTVal158Met, CYP17-34T>C, CYP191558C>T, CYP19Arg264Cys, CYP1A16235T>C, CYP1A1Ile462Val, CYP1B1Leu432Val, CYP1B1Asn453Ser, HSD17B1-27A>C, ER-alphaIVS-401T>C, prothrombin20210G>A, factor V Leiden, eNOS-786T>C, eNOSGlu298Asp, MRSer810Leu, MTHFR677C>T, PAI 15G>4G, SRD5A2Val89Leu, and VDRb>B.


RESULTS
Among the women in the study, 66% had at least two homozygous mutant SNPs of interest. A thrombophilic disposition was found in 9.9% of women, and 23% of women had at least two SNPs associated with an increased risk of breast cancer (COMT, CYP17, CYP19, CYP1A1, and CYP1B1). The SNPs predisposing women to cardiovascular pathologies (e.g., APOE, AGT, eNOS, and PAI 1) were found in 12.3% of women. Carriage of SNPs predisposing to early postmenopausal bone loss and osteoporosis (ER-alpha and VDR) were found in 26.7% of women.


CONCLUSIONS
These data suggest that the assessment of SNPs associated with risks and benefits of estrogen/hormone therapy may be a new means to individualize counseling about and prescription of estrogen/hormone therapy in up to 66% of women.
Tempfer
Clemens B
CB
Department of Obstetrics and Gynecology, University of Freiburg Medical School, Freiburg, Germany. tempfer@frk.ukl.uni-freiburg.de
Riener
Eva-Katrin
EK
Hefler
Lukas A
LA
Huber
Johannes C
JC
Muendlein
Axel
A
D001943:Breast Neoplasms / Q000139:chemically induced / Q000235:genetics; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000235:genetics; D003430:Cross-Sectional Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006579:Heterozygote; D006720:Homozygote; D020249:Hormone Replacement Therapy / Q000009:adverse effects*; D006801:Humans; D015994:Incidence; D020411:Oligonucleotide Array Sequence Analysis; D010024:Osteoporosis / Q000139:chemically induced / Q000235:genetics; D015663:Osteoporosis, Postmenopausal / Q000139:chemically induced / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment