Objective To determine what percentage of women can be given individu alized co unseling based on genetic information, as single nucleotide polymorphisms (SNPs) are associated with risks and benefits of estrogen thera...Objective To determine what percentage of women can be given individu alized co unseling based on genetic information, as single nucleotide polymorphisms (SNPs) are associated with risks and benefits of estrogen therapy and hormone therapy such as thrombosis, myocardial infarction, breast cancer, and bone protection. D esign Cross-sectional study. Setting Academic research institution. Patient(s) A consecutive series of 2,507 perimenopausal and postmenopausal women. Intervent ion(s) Peripheral venous puncture and multiplex polymerase chain reaction on a m icroarray system. Main outcome measure(s) Analysis of 22 SNPs of 17 genes: AGTMe t235Thr, APOECys112Arg, APOEArg158-Cys, COMTVal158Met, CYP17-34T >C, CYP191558 C >T, CYP19Arg264Cys, CYP1A16235T >C, CYP1A1Ile462Val, CYP1B1Leu432Val, CYP1B1A -sn453Ser, HSD17B1-27A >C, ER-αIVS-401T >C, prothrombin20210G >A, factor V Leiden, eNOS-786T >C, eNOSGlu298Asp, MRSer810L eu, MTHFR677C >T, PAI 15G >4G, SRD5A2Val89Leu, and VDRb >B. Result(s) Among the women in the study, 66%had at least two homozygous mutant SNPs of interest. A t hrombophilic disposition was found in 9.9%of women, and 23%of women had at lea st two SNPs associated with an increased risk of breast cancer (COMT, CYP17, CYP 19, CYP1A1, and CYP1B1). The SNPs predisposing women to cardiovascular pathologi es (e.g., APOE, AGT, eNOS, and PAI 1) were found in 12.3%of women. Carriage of SNPs predisposing to early postmenopausal bone loss and osteoporosis (ER-αand VDR) were found in 26.7%of women. Conclusion( s) These data suggest that the as sessment of SNPs associated with risks and benefits of estrogen/hormone therapy may be a new means to individualize counseling about and prescription of estroge n/hormone therapy in up to 66%of women.展开更多
N-ethyl-N-nitrosourea （ENU） mutagenesis in mice can be used to study gene function in vivo and to establish genetic mouse models of human disease. In this study, a white spotted mouse （named Kit^W-1 Bao） was obtai...N-ethyl-N-nitrosourea （ENU） mutagenesis in mice can be used to study gene function in vivo and to establish genetic mouse models of human disease. In this study, a white spotted mouse （named Kit^W-1 Bao） was obtained by ENU-induced mutagenesis. Inheritance testing showed a single-gene dominant mutation and lethality in the Kit^W-1 Bao homozygous mice. The mutation was mapped to Chromosome 5 between markers DSMit356 and DSMit308. The region contains the Kit gene, whose mutations are known to lead to pigmentation defects in mice. Sequence analysis of the Kit cDNA from Kit^W-1 Bao heterozygotes revealed an A to T missense mutation resulting in an amino acid substitution of Asp （D） by Val （V） at amino acid position 849 within a highly conserved tyrosine kinase domain. The combined phenotype displayed by the Kit^W-1 Bao heterozygous and homozygous mutant mice demonstrates the critical function of the highly conserved aspartie acid residue at position 849 in the Kit gene product展开更多
文摘Objective To determine what percentage of women can be given individu alized co unseling based on genetic information, as single nucleotide polymorphisms (SNPs) are associated with risks and benefits of estrogen therapy and hormone therapy such as thrombosis, myocardial infarction, breast cancer, and bone protection. D esign Cross-sectional study. Setting Academic research institution. Patient(s) A consecutive series of 2,507 perimenopausal and postmenopausal women. Intervent ion(s) Peripheral venous puncture and multiplex polymerase chain reaction on a m icroarray system. Main outcome measure(s) Analysis of 22 SNPs of 17 genes: AGTMe t235Thr, APOECys112Arg, APOEArg158-Cys, COMTVal158Met, CYP17-34T >C, CYP191558 C >T, CYP19Arg264Cys, CYP1A16235T >C, CYP1A1Ile462Val, CYP1B1Leu432Val, CYP1B1A -sn453Ser, HSD17B1-27A >C, ER-αIVS-401T >C, prothrombin20210G >A, factor V Leiden, eNOS-786T >C, eNOSGlu298Asp, MRSer810L eu, MTHFR677C >T, PAI 15G >4G, SRD5A2Val89Leu, and VDRb >B. Result(s) Among the women in the study, 66%had at least two homozygous mutant SNPs of interest. A t hrombophilic disposition was found in 9.9%of women, and 23%of women had at lea st two SNPs associated with an increased risk of breast cancer (COMT, CYP17, CYP 19, CYP1A1, and CYP1B1). The SNPs predisposing women to cardiovascular pathologi es (e.g., APOE, AGT, eNOS, and PAI 1) were found in 12.3%of women. Carriage of SNPs predisposing to early postmenopausal bone loss and osteoporosis (ER-αand VDR) were found in 26.7%of women. Conclusion( s) These data suggest that the as sessment of SNPs associated with risks and benefits of estrogen/hormone therapy may be a new means to individualize counseling about and prescription of estroge n/hormone therapy in up to 66%of women.
基金supported by the National Natural Science Foundation of China(NO.30670231)Public Service Project of Lab Animal Science(NO.2008F80005)SRF for ROCS,SEM
文摘N-ethyl-N-nitrosourea （ENU） mutagenesis in mice can be used to study gene function in vivo and to establish genetic mouse models of human disease. In this study, a white spotted mouse （named Kit^W-1 Bao） was obtained by ENU-induced mutagenesis. Inheritance testing showed a single-gene dominant mutation and lethality in the Kit^W-1 Bao homozygous mice. The mutation was mapped to Chromosome 5 between markers DSMit356 and DSMit308. The region contains the Kit gene, whose mutations are known to lead to pigmentation defects in mice. Sequence analysis of the Kit cDNA from Kit^W-1 Bao heterozygotes revealed an A to T missense mutation resulting in an amino acid substitution of Asp （D） by Val （V） at amino acid position 849 within a highly conserved tyrosine kinase domain. The combined phenotype displayed by the Kit^W-1 Bao heterozygous and homozygous mutant mice demonstrates the critical function of the highly conserved aspartie acid residue at position 849 in the Kit gene product
