RESUMEN
OBJECTIVE: Sex hormone binding globulin (SHBG) levels are often low in women with polycystic ovary syndrome (PCOS). In addition to metabolic and nutritional factors, SHBG levels are determined by genetic polymorphisms in SHBG gene. The aim of this study was to investigate the association of polymorphisms in exon 8 of SHBG gene with anthropometric and biochemical features of women with PCOS. DESIGN: Prospective, observational study. PATIENTS: One hundred and ninety-four women with PCOS. MAIN OUTCOME MEASURE(S): Genotype analysis of exon 8 in SHBG gene was performed. Serum SHBG, total testosterone, free testosterone, 17-α-hydroxyprogesterone, TSH, PRL, glucose and insulin levels were determined. MAIN FINDING(S): Single nucleotide polymorphism (SNP) E326K located at codon 326 in exon 8 of SHBG gene was identified. Serum SHBG levels decreased significantly with increasing copy number of the variant allele for SNP E326K after adjustment for BMI, androgenic and insulin-related traits. Genotype analysis also revealed SNP, rs6259, located at codon 327 in exon 8 of SHBG gene, which is not associated with SHBG levels. CONCLUSION: SNP, E326K, in exon 8 of SHBG gene may influence the metabolism of SHBG independently of BMI, androgenic and insulin-related features in women with PCOS.
Asunto(s)
Exones , Resistencia a la Insulina/genética , Síndrome del Ovario Poliquístico/genética , Polimorfismo de Nucleótido Simple , Globulina de Unión a Hormona Sexual/genética , Adulto , Alelos , Glucemia , Índice de Masa Corporal , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Insulina/sangre , Síndrome del Ovario Poliquístico/sangre , Prolactina/sangre , Estudios Prospectivos , Globulina de Unión a Hormona Sexual/metabolismo , Testosterona/sangre , Tirotropina/sangreAsunto(s)
Mutación/genética , Síndrome de Netherton/diagnóstico , Diagnóstico Preimplantación , Diagnóstico Prenatal , Proteínas Inhibidoras de Proteinasas Secretoras/genética , Adulto , Secuencia de Bases , Blastómeros/citología , Transferencia de Embrión , Femenino , Fertilización In Vitro , Humanos , Masculino , Datos de Secuencia Molecular , Síndrome de Netherton/complicaciones , Síndrome de Netherton/genética , Oligospermia/terapia , Síndrome del Ovario Poliquístico/terapia , Embarazo , Inhibidor de Serinpeptidasas Tipo Kazal-5 , Inyecciones de Esperma IntracitoplasmáticasRESUMEN
NLRP7 is a major gene responsible for recurrent hydatidiform moles. Here, we report 11 novel NLRP7 protein truncating variants, of which five deletions of more than 1-kb. We analyzed the transcriptional consequences of four variants. We demonstrate that one large homozygous deletion removes NLRP7 transcription start site and results in the complete absence of its transcripts in a patient in good health besides her reproductive problem. This observation strengthens existing data on the requirement of NLRP7 only for female reproduction. We show that two other variants affecting the splice acceptor of exon 6 lead to its in-frame skipping while another variant affecting the splice donor site of exon 9 leads to an in-frame insertion of 54 amino acids. Our characterization of the deletion breakpoints demonstrated that most of the breakpoints occurred within Alu repeats and the deletions were most likely mediated by microhomology events. Our data define a hotspot of Alu instability and deletions in intron 5 with six different breakpoints and rearrangements. Analysis of NLRP7 genomic sequences for repetitive elements demonstrated that Alu repeats represent 48% of its intronic sequences and these repeats seem to have been inserted into the common NLRP2/7 primate ancestor before its duplication into two genes.