Candidate genes and Heritability of PCO

 

Heritability Of PCO & Candidate genes??

PCOS  seems to  run within families and  although  50%  of all sisters  were  unaffected only 25%   had a similar   phenotype   compared  to the proband  whereas  the remaining 25% suffered from  hyperandrogenemia   . In subsequent   studies  it was   shown that brothers  of women with  PCOS   have dyslipidemia as well as     evidence    for insulin resistance similar   to that of   their proband sisters  with  PCOS. More  recently   evidence emerged   indicating   clustering of metabolic syndrome , hypertension and dyslipidemia in mothers  , fathers   sisters,  and brothers  of women   with PCOS.

Twin studies revealed    similar  results indicating a familial   component   in PCOS  is due to genetic  factors. The resemblance  in monozygotic twin   sisters   for PCOS   was about   twice as large  as in dizygotic twin  pairs   indicating a high degree of heritability.

 

Candidate  gene  studies

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.