Research On SNPs Of GDF-9and BMP-15Gene In Ningxia Women With Premature Ovarian Failure

Objective To evaluate the correlation between the SNPs of growth differentiationfactor-9（GDF-9）/bone morphogenetic protein-15（BMP-15）gene and Ningxia wowenwith premature ovarian failure （POF）, as the digit length ratio （DLR） of POF,inorder to investigate the nosetiology of POF and pre-interfering for POF.Methods63women with POF and62normal women （controls） were recruited fromFeb.2010to Aug.2011. To analyze chromosome karyotype by GRQ technology, GDF-9and BMP-15gene mutations by PCR-restriction fragment length polymorphism（PCR-RFLP） and the direct sequencing methods, DLR for left and right hands withthe electronic sliding caliper.Results （1）There were four mutation sites in the GDF-9gene protein codingregion:c.169G＞T（p.D57Y）、 c.546G＞A、 c.447C＞T and c.969C＞G,and thefrequencies of c.546G＞A as well as its A allele were significantly higher inPOF group than controls （34.92%vs.6.45%,19.05%vs.3.23%, respectively, allp<0.05）.（2）There was significant difference of the mutation rate and allelicfrequencies of c.447C＞T/c.969C＞G between Hui people with POF and Hui controls（68.96%vs.38.46%and3.10%vs.21.15%,62.07%vs.34.62%and39.66%vs.21.15%,respectively, all p＜0.05）.（3）It occurred to three mutation sites in the BMP-15gene protein coding region: c.-9C＞G/c.788₇89insTCT for exon1, and c.852C＞T for exon2.（4）FSH、LH levels in serum were higher in POF goup than controls（73.85±24.41vs6.14±2.02,50.80±17.83vs4.05±1.66, respectively, all p ＜0.01）, however, PRL、E2and T levels were dramatically lower （8.39±4.39vs.13.08±5.45，11.22±8.33vs.42.59±14.18,2.53±16.08vs.42.85±13.52,respectively, all p＜0.01）.（5）The abnormal karyotype in POF group accountedfor6.34%.（6）DLRs of2D:5D/3D:4D/3D:5D/4D:5D at the left hand of the POF Groupwere significantly higher than that of the controls（all p＜0.05）.（7）D（l-r）of L24-R24、L25-R25、L35-R35and L45-R45in POF Group were increasing thancontrols（all p＜0.05）.Conclusions（1）There are regional differences in the mutation sites c.169G＞T（p.D57Y） and c.546G＞A of the GDF-9gene,which could be closely related tothe incidence of Ningxia women with POF.（2）The mutation rates of c.447C>T andc.969C>G in Hui women with POF are higher than controls，indicating that thevariants play important role in Hui people with POF.（3）The mutation sitec.788₇89insTCT of BMP-15gene could have been one of genetic factors in Ningxiawomen with POF.（4）The interaction between GDF-9and FSHR are not exist，itis possible impact from the different aspects of POF.（5）The left DLR servesas the early parameter for POF diagnosis, pretending that it is related to sexhormone within maternal uterus.