학술논문
The Immunosignature of Mother/Fetus Couples in Gestational Diabetes Mellitus: Role of HLA-G 14 bp ins/del and PAPP-A A/C Polymorphisms in the Uterine Inflammatory Milieu.
Document Type
Academic Journal
Author
Martinetti M; Immunogenetics Laboratory, Immunohematology and Transfusion Center, IRCCS Policlinico San Matteo Foundation, Pavia, Italy.; Beneventi F; Department of Obstetrics and Gynecology, IRCCS Policlinico San Matteo Foundation and University of Pavia, Pavia, Italy.; Capittini C; Clinical Epidemiology and Biometric Unit, IRCCS Policlinico San Matteo Foundation, Pavia, Italy.; Locatelli E; Department of Obstetrics and Gynecology, IRCCS Policlinico San Matteo Foundation and University of Pavia, Pavia, Italy.; Simonetta M; Department of Obstetrics and Gynecology, IRCCS Policlinico San Matteo Foundation and University of Pavia, Pavia, Italy.; Cavagnoli C; Department of Obstetrics and Gynecology, IRCCS Policlinico San Matteo Foundation and University of Pavia, Pavia, Italy.; De Maggio I; Department of Obstetrics and Gynecology, IRCCS Policlinico San Matteo Foundation and University of Pavia, Pavia, Italy.; De Silvestri A; Clinical Epidemiology and Biometric Unit, IRCCS Policlinico San Matteo Foundation, Pavia, Italy.; Pasi A; Immunogenetics Laboratory, Immunohematology and Transfusion Center, IRCCS Policlinico San Matteo Foundation, Pavia, Italy.; Spinillo A; Department of Obstetrics and Gynecology, IRCCS Policlinico San Matteo Foundation and University of Pavia, Pavia, Italy.
Source
Publisher: Hindawi Pub. Corp Country of Publication: United States NLM ID: 8604127 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1875-8630 (Electronic) Linking ISSN: 02780240 NLM ISO Abbreviation: Dis Markers Subsets: MEDLINE
Subject
Language
English
Abstract
We enrolled 151 healthy mother/newborn couples and 26 with gestational diabetes mellitus (GDM). HLA-G and PAPP-A plasma levels were measured by ELISA at first and second trimesters, at delivery, and in cord blood. HLA-G 14 bp ins/del and PAPP-A A/C polymorphisms were genotyped. HLA-G del/del and PAPP-A C/C genotypes were more frequent among GDM mothers than controls. We observed a genetic epistasis between the two polymorphisms: the HLA-G del/del and PAPP-A C/C combination was carried by 8% of GDM mothers and 1.3% of controls (OR = 9.5, 95% CI = 0.8-109, p = 0.07). GDM mothers showed increased sHLA-G levels compared to controls ( p = 0.004), and those carrying the HLA-G del/del genotype produced more sHLA-G at the second trimester and at delivery ( p = 0.014). A genetic pressure by fetal genotype on maternal sHLA-G production was observed in GDM mothers with heterozygous HLA-G del/ins newborns ( p = 0.02). Babies born to GDM mothers showed higher sHLA-G concentrations compared to those born to healthy mothers, and those carrying HLA-G del/del showed the highest sHLA-G levels ( p = 0.013). PAPP-A amounts significantly increased along pregnancy ( p < 0.001), but the median levels at the first and second trimesters were significantly lower in GDM ( p = 0.03). Our findings first suggest an involvement of HLA-G and PAPP-A gene-protein interaction in GDM and highlight a possible contribution of the fetus in balancing maternal inflammation.