Candidate gene region for polycystic ovary syndrome on chromosome 19p13.2.
BACKGROUND
Polycystic ovary syndrome (PCOS) is a common endocrine disorder that is believed to have a genetic basis. However, no specific susceptibility gene or region has been conclusively identified.


OBJECTIVE
The objective of this study was to duplicate a previous study that localized a PCOS susceptibility region to chromosome 19p13.2 and to narrow the susceptibility region.


METHODS
This study was designed to test for genetic linkage and association between PCOS and short tandem repeat polymorphisms in 367 families, by analysis of linkage and family-based association.


METHODS
The study was conducted at academic medical centers.


METHODS
We studied 367 families of predominantly European origin with at least one PCOS patient. Families included 107 affected sibling (sister) pairs (ASPs) in 83 families, and 390 trios with both parents and an affected daughter. The data set comprises two independent groups. Set 1 consists of 44 ASPs and 163 trios. Set 2 consists of 63 ASPs and 227 trios.


METHODS
The intervention was the drawing of blood for DNA extraction.


METHODS
We employed measures of evidence for linkage and association between PCOS and 19 STRs.


RESULTS
Linkage with PCOS was observed over a broad region of chromosome 19p13.2. The strongest evidence for association was observed with D19S884 (chi2 = 11.85; nominal P < 0.0006; permutation P = 0.034) and duplicated our earlier findings.


CONCLUSIONS
The present analysis suggests that a PCOS susceptibility locus maps very close to D19S884. Additional studies that systematically characterize DNA sequence variation in the immediate area of D19S884 are required to identify the PCOS susceptibility variant.
Urbanek
M
M
Division of Endocrinology, Metabolism, and Molecular Medicine, Northwestern University School of Medicine, 303 East Chicago Avenue, Tarry 15-717, Chicago, Illinois 60611, USA. m-urbanek@northwestern.edu
Woodroffe
A
A
Ewens
K G
KG
Diamanti-Kandarakis
E
E
Legro
R S
RS
Strauss
J F
JF
Dunaif
A
A
Spielman
R S
RS
D000328:Adult; D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D011085:Polycystic Ovary Syndrome / Q000235:genetics*; D035781:Siblings; D020080:Tandem Repeat Sequences