Allele, Genotype and Haplotype Structures of Functional Polymorphic Variants in Endothelial Nitric Oxide Synthase (eNOS), Angiotensinogen (ACE) and Aldosterone Synthase (CYP11B2) Genes in Healthy Pregnant Women of Indian Ethnicity.
BACKGROUND
Variants in the candidate genes eNOS, CYP11B2 and ACE have been implicated as liable biomarkers that can predict complications like hypertension and preeclampsia. Studies on the impact and distribution of these variants on healthy pregnancy have not been done so far in south Indian or in any of the native Indian population. Examining these variants could lay a strong basis in understanding the genetic aspects of preeclampsia and further offer effective means in early risk assessment in a preeclampsia.


METHODS
Genotyping for 303 unrelated healthy women of Tamilian origin who underwent uncomplicated term pregnancies was executed by PCR-RFLP for eNOS, CYP11B2 and ACE variants. Haplotype assessment and pairwise linkage disequilibrium (LD) investigation were performed by Haploview software.


RESULTS
The prevalence of eNOS variants (-786T>C, Glu298Asp and intron 4 VNTR) was 12%, 21.6% and 21.1%, respectively. The incidence of CYP11B2 (-344 C>T) and ACE (287 bp Alu I/D) variants was found to be 43.8% and 42.7%. The observed frequencies of the studied polymorphisms did not diverge from the HWE (p>0.05). Significant LD was observed between 3 eNOS gene polymorphisms. Six different haplotype structures with a frequency of >1% were generated from three eNOS variants. Among the haplotypes generated, the haplotype T-4b-G was the most common with the frequency of 64.4%. There was a statistically significant inconsistency in the study population in comparison to other global races.


CONCLUSIONS
The outcome of this study could be used for investigating future therapeutic value of the variants in a preeclamptic set-up which could pose a credible diagnostic potential for primary risk assessment of women susceptible to preeclampsia/other pregnancy related complications.
Department of Pharmacology, Jawaharlal Institute of Post Graduate Medical Education and Research (JIPMER), Pondicherry, India.
Anichavezhi
A
Devendran
Department of Biotechnology and Biochemical Engineering, Sree Buddha College of Engineering, Alappuzha, Kerala, India.
Sreekala
S
Nampoothiri
Department of Pharmacology, Jawaharlal Institute of Post Graduate Medical Education and Research (JIPMER), Pondicherry, India.
Deepak Gopal
DG
Shewade
Vascular Biology Division, AU-KBC Research Centre, Madras Institute of Technology (M.I.T), Anna University, Chrompet, Chennai, India.
Suvro
S
Chatterjee
Department of Cardiology, Jawaharlal Institute of Post Graduate Medical Education and Research (JIPMER), Pondicherry, India.
Balachandar
B
Jayaraman
Department of Pharmacology, Jawaharlal Institute of Post Graduate Medical Education and Research (JIPMER), Pondicherry, India.
Adithan
A
Chandrasekharan
CYP11B2; Haplotypes; Hypertension; Preeclampsia; eNOS