Affiliations: Human Molecular Genetics Laboratory, Rajiv Gandhi
Centre for Biotechnology, Thiruvananthapuram, Kerala, India | Sree Chitra Tirunal Institute for Medical Science and
Technology, Thiruvananthapuram, Kerala, India
Note: [] Corresponding author: Moinak Banerjee, Ph.D, Human Molecular
Genetics Laboratory, Rajiv Gandhi Centre for Biotechnology, Thycaud P.O.,
Thiruvananthapuram-695014, Kerala, India. Tel.: +91 471 2341716; Fax: +91 471
2348096; E-mail: [email protected]; [email protected]
Abstract: Endothelial nitric oxide synthase (eNOS) gene polymorphisms
have been implicated as predisposing genetic factors that can predict
aneurysmal subarachnoid hemorrhage (aSAH), but with controversial results from
different populations. Using a case-control study design, we tested the
hypothesis whether variants in eNOS gene can increase risk of aSAH among
South Indian patients, either independently, or by interacting with other risk
factors of the disease. We enrolled 122 patients, along with 224 ethnically
matched controls. We screened the intron-4 27-bp VNTR, the promoter T-786C and
the exon-7 G894T SNPs in the eNOS gene. We found marked interethnic
differences in the genotype distribution of eNOS variants when comparing
the South Indian population with the reported frequencies from Caucasian and
Japanese populations. Genotype distributions in control and patient populations
were found to be in Hardy-Weinberg equilibrium. In patients, the allele,
genotype and estimated haplotype frequencies did not differ significantly from
the controls. Multiple logistic regression indicated hypertension and smoking
as risk factors for the disease, however the risk alleles did not have any
interaction with these risk factors. Although the eNOS polymorphisms were
not found to be a likely risk factor for aSAH, the role of factors such as
ethnicity, gender, smoking and hypertension should be evaluated cautiously to
understand the genotype to phenotype conversion.
Keywords: eNOS, SNP, aneurysm, subarachnoid hemorrhage, India
