title: MTHFR (C677T) CT genotype and CT-apoE3/3 genotypic combination predisposes the risk of ischemic stroke.
abstract: The predisposition to ischemic stroke (IS) might involve interactions of several genes and environmental factors. The present study was aimed to evaluate the influence of polymorphisms in methylenetetrahydrofolate reductase (MTHFR-C677T) and apolipoprotein-E (apo-E) as risk factors for IS patients in south Indian population. 200 IS patients and 193 age and sex matched controls were genotyped for MTHFR-C677T and apoE by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method. Statistically significant association was observed for MTHFR CT genotype (IS-Pooled: OR=4.29; p=5.01×10(-5); IS-Males: OR=4.13; p=0.001; IS-Females: OR=8.62; p=0.027; IS-Large Vessel Disease (LVD)- Pooled: OR=4.14; p=0.0002) and T allele (IS-Pooled: OR=4.82; p=1.49×10(-5); IS-Males: OR=4.33; p=0.0002; IS-Females: OR=7.99; p=0.031; IS-LVD-Pooled: OR=4.13; p=0.0001). Further, reduced frequencies of CC genotype (IS-Pooled: OR=0.20; p=9.80×10(-6); IS-Males: OR=0.25; p=0.001; IS-Females: OR=0.12; p=0.027; IS-LVD-Pooled: OR=0.23; p=0.0001) and C allele (IS-Pooled: OR=0.21; p=1.49×10(-5); IS-Males: OR=0.23; p=0.0002; IS-Females: OR=0.13; p=0.031; IS-LVD-Pooled: OR=0.24; p=0.0001) were observed in IS patients than the controls. No association was observed for apoE genotypes/alleles in IS/LVD cases. Our study demonstrated the presence of risk for MTHFR CT genotype/T allele and 'CT-3/3' (n=33 vs. 5; OR=7.42; p=0.001) genotypic combination in the development of IS in south India. Further, follow-up study of these stroke cases i.e., in later stages of the disease whether they are developing the neurological disorders such as Alzheimer's Disease (AD) and vascular dementia (VaD) is needed to draw a fruitful conclusion in connection between neurological disorders and with these two polymorphisms, before translating it into clinical practice.
authors.affiliation: Department of Biotechnology & Genetic Engineering, School of Biotechnology, Bharathidasan University, Tiruchirappalli 620 024, Tamil Nadu, India; Department of Immunology, School of Biological Sciences, Madurai Kamaraj University, Madurai 625 021, Tamil Nadu, India.
authors.forename: Murali
authors.initials: M
authors.lastname: Vijayan
authors.affiliation: Department of Immunology, School of Biological Sciences, Madurai Kamaraj University, Madurai 625 021, Tamil Nadu, India.
authors.forename: Rathika
authors.initials: R
authors.lastname: Chinniah
authors.affiliation: Department of Immunology, School of Biological Sciences, Madurai Kamaraj University, Madurai 625 021, Tamil Nadu, India.
authors.forename: Padma Malini
authors.initials: PM
authors.lastname: Ravi
authors.affiliation: Department of Immunology, School of Biological Sciences, Madurai Kamaraj University, Madurai 625 021, Tamil Nadu, India.
authors.forename: Ramgopal
authors.initials: R
authors.lastname: Sivanadham
authors.affiliation: Hannah Joseph Hospital, Lake View Road, K. K. Nagar, Madurai 625 020, India.
authors.forename: Arun Kumar
authors.initials: AK
authors.lastname: Mosses Joseph
authors.affiliation: Neethi Arasu Neuro Hospital, Sivagangai Road, Madurai, 625 020, India.
authors.forename: Neethi Arasu
authors.initials: NA
authors.lastname: Vellaiappan
authors.affiliation: Narayana Institute Health City, Bangalore 560 099, India.
authors.forename: Jeyaram Illiayaraja
authors.initials: JI
authors.lastname: Krishnan
authors.affiliation: Department of Immunology, School of Biological Sciences, Madurai Kamaraj University, Madurai 625 021, Tamil Nadu, India. Electronic address: immunobala@mkuniversity.org.
authors.forename: Balakrishnan
authors.initials: B
authors.lastname: Karuppiah
mesh_terms: D000483:Alleles; D001057:Apolipoproteins E / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D020521:Stroke / Q000235:genetics*
chemical_list: C000612345:ApoE protein, human; D001057:Apolipoproteins E; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)
keywords: AD; Genotype; Ischemic stroke; LVD; MTHFR C677T; Synergistic effect; apoE