Association between fragile X premutation and premature ovarian failure: a case-control study and meta-analysis.
OBJECTIVE
The aim of the present study was to investigate the association between FMR1 premutation and premature ovarian failure (POF) patients in Indian population, and a meta-analysis of published results was undertaken to clarify whether FMR1 premutation consistently contributed to the susceptibility.


METHODS
A total of 289 POF samples and 360 control samples were included in the study. Repeat variation was checked using GeneScan technique. Results were analyzed with GeneMapper software. Meta-analysis was performed using the Open Meta-Analyst and STATA 12.0 software. The crude odds ratio with 95 % confidence interval (CI) was computed to assess the strength of the associations.


RESULTS
The assayed case and control population showed 29 different CGG repeat sizes (alleles), ranging from 7 to 40. Within this population, we found that the CGG repeat length polymorphisms were within the normal range of 6-55 in both patients as well as control samples. Eleven case-control studies were included in the meta-analysis with a total of 1,313 POF cases and 3,132 control subjects. Our meta-analysis revealed that there was a significant difference in the incidence of FMR1 premutation between POF cases and control subjects with p value <0.001 (OR 5.41; 95 % CI 2.53, 11.61).


CONCLUSIONS
We found no significant association between FMR1 CGG repeat premutation and POF in Indian population. However, the meta-analysis showed an increased risk of POF associated with a premutation, especially among populations from European descent. Further functional research should be performed to explain the inconsistent results in different ethnicities and POF susceptibility.
Biology Division, CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad, 500 007, India.
Durgadatta
D
Tosh
K Lakshmi
KL
Rao
H Surekha
HS
Rani
D Anupama
DA
Deenadayal
U S N
US
Murty
Paramjit
P
Grover
D000328:Adult; D016022:Case-Control Studies; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007194:India; D009154:Mutation; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D016649:Primary Ovarian Insufficiency / Q000235:genetics*
D051860:Fragile X Messenger Ribonucleoprotein 1; C497683:FMR1 protein, human