In PCOS candidate
genes have been studies that
were involved in the biosynthesis and trafficking of androgens, genes related
to metabolic aspects of
PCOS and genes correlated
with inflammatory cytokines. Currently
more than 200 studies have been
reporting on SNP( single nucleotide polymorphisms) in genes
involved in these pathways.
Numerous studies have been reporting on other
SNPs in genes that are
associated with either the risk of having PCOS or one of its characteristic features. However the majority of these
studies are small and lack proper
replication studies and should
therefore be interpreted with
caution.
A
potential association of the D195884 marker in the fibrillin gene with PCOS
in Chinese women
was found . A meta analysis identified that allele 8 may increase
a women ‘s susceptibility to PCOS
.
Genes involved in androgen metabolism have
been studied extensively . Two SNPs
in the promotor region of the
genes encoding for CYP17A1 and CYP11A1 were associated with serum
androgen levels in a subset of Indian
women. However a recent metaanalysis
failed to verify this
relationship .
The androgen receptor has also
been studied in relation to PCOS
susceptibility and the
associated hyperandrogenism.
However a recent meta analysis
including 1536 PCOS patients and 1807 controls
revealed that the
lengths of CAG repeats
in the AR contributed to hyperandrogenism in PCOS.
In a recent
meta analysis including 12 studies
only one single nucleotide
polymorphism in the “Fat Mass
and Obesity associated gene”-- did
significantly increase the risk
of PCOS in women. However , two
other SNP’s were associated with PCOS
only in a recessive model.
Given the
increased risk for type 2 diabetes and
the insulin resistance frequently
encountered in women with PCOS into
account the insulin receptor gene also
has been studied frequently . In a recent meta analysis a total of 20 case control studies
including 23, 845 controls and
17, 460 PCOS cases were analyzed
and only
17 SNPs were found to be associated with PCOS.
Further subgroup
stratification by ethnicity and weight
did not lead to discovery of
significant correlation. Only one other
SNP e.g.
2059807 was associated with PCOS.
The current meta analysis
suggests no significant correlation between
both SNPs
rs1799817/rs2059807 was
associated with PCOS.
Insulin receptor
substrates although
significantly associate with PCOS in Japanese and Greek population
a recent meta analysis of 11
studies did not reveal
a significant association between
IRS 1 SNPs and the risk to develop PCOS.
A
recent meta analysis revealed
no significant association between
INS VNTR polymorphisms and the risk of PCOS
in the overall population .
There are
several FSH receptor
polymorphisms located in the FSHR
gene. The two most common are the Thr307 Ala and Asn680Ser
polymorphisms. A total of 11
studies were included in a recent metaanalysis . The Asn680Ser variant is significantly associated with treatment outcome
and pregnancy rates in ovulation induction . no significant
association were found between
Thr30 7Ala and PCOS.
More
recently based on the fact that AMH
serum levels are increased
in women with PCOS SNPs in the AMH gene as well as in the AMH
Type ll Receptor gene have
been studied. Neither SNPs in
the AMH gene
nor those in the AMHR2 did
confer a heightened risk
for PCOS. The results of a
meta analysis including
13 studies , assessing the role of
different TNF alpha SNPs and PCOS
susceptibility suggests a positive
associations between one TNF alpha SNP and the risk of PCOS.
However no association were
detected between another 9 SNPs
in the TNF alpha gene and
the risk for PCOS. Another meta analysis including
a total of 14 studies
investigated the association of SNPs in the interleukins lL-6 and lL- 1 beta and did not
find a significant
relationship with the susceptibility for PCOS.
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