title: TGFB1 Functional Gene Polymorphisms (C-509T and T869C) in the Maternal Susceptibility to Pre-eclampsia in South Indian Women.
abstract: Pre-eclampsia (PE), a pregnancy-specific vascular disorder characterized by hypertension and proteinuria, is hypothesized to be the result of inadequate placental angiogenesis with attendant systemic inflammation. The pleiotropic cytokine, Transforming Growth Factor-β1 (TGF-β1), is considered to be a key candidate gene in the molecular pathogenesis of PE by virtue of its ability to not only regulate angiogenesis and apoptosis of target cells, but also by acting as a master controller of Th1/Th2 cytokine balance and production of the anti-inflammatory peripheral regulatory T cells (FOXP3+ Tregs). Based on this presumption, we screened a total of 469 pregnant women from South India that include 239 patients with PE and 230 healthy controls for the two functional polymorphisms of TGFB1 gene (C-509T and T869C). The genotype frequencies of these two polymorphisms differed significantly between the PE and control groups (P = 0.01 and P = 0.002, for the TGFB1 C-509T and T869C polymorphisms, respectively). Under the over-dominant model, the CT genotype of the TGFB1 C509T polymorphism showed a high protective effect (P = 3e-04), while the TT genotype of the same variant appeared to be the predisposing genotype (P = 0.003). The T-T and C-C haplotypes were found to be the risk haplotypes blocks towards PE (OR = 4.72; P = 0.031, OR = 5.39; P = 0.03), respectively. Strong linkage disequilibrium was seen between the two polymorphisms. Our investigations revealed a significant influence of TGFB1 C-509T and T869C polymorphisms on the PE risk in South Indian women. The study represents one of the first of its kind from the Indian subcontinent.
authors.affiliation: Department of Genetics, Osmania University, Hyderabad, India.
authors.forename: Goske
authors.initials: G
authors.lastname: Deepthi
authors.affiliation: Department of Genetics, Osmania University, Hyderabad, India.
authors.forename: Ponnaluri Kamakshi
authors.initials: PK
authors.lastname: Chaithri
authors.affiliation: Department of Genetics, Osmania University, Hyderabad, India.
authors.forename: Prasanna
authors.initials: P
authors.lastname: Latha
authors.affiliation: Department of Obstetrics and Gynecology, MG Hospital, Petlaburz, Hyderabad, India.
authors.forename: Vital Usha
authors.initials: VU
authors.lastname: Rani
authors.affiliation: Department of Zoology, School of Sciences, Maulana Azad National Urdu University, Hyderabad, India.
authors.forename: Police Fazul
authors.initials: PF
authors.lastname: Rahman
authors.affiliation: Department of Genetics, Osmania University, Hyderabad, India.|Department of Zoology, School of Sciences, Maulana Azad National Urdu University, Hyderabad, India.
authors.forename: Parveen
authors.initials: P
authors.lastname: Jahan
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007194:India; D015810:Linkage Disequilibrium / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011225:Pre-Eclampsia / Q000235:genetics*; D011247:Pregnancy; D012306:Risk; D053773:Transforming Growth Factor beta1 / Q000235:genetics*; D055815:Young Adult
chemical_list: C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1