Identification and analysis of novel mutations in NFKBIL1 gene in patients with Myocardial infarction (MI) in south India

Kanavath Sreedhar Naik; Durgaprasad Rajasekhar; Velam Vanajakshamma; Pasupuleti Santhosh Kumar; Doddipalli Sreenivasa Reddy; Potukuchi Venkata Gurunadha Krishna Sarma

Volume : VII, Issue : V, May - 2018

Identification and analysis of novel mutations in NFKBIL1 gene in patients with Myocardial infarction (MI) in south India

Kanavath Sreedhar Naik, Durgaprasad Rajasekhar, Velam Vanajakshamma, Pasupuleti Santhosh Kumar, Doddipalli Sreenivasa Reddy, Potukuchi Venkata Gurunadha Krishna Sarma

Abstract :

NF–kappa–B inhibitor–like protein 1(NFKBIL1) genelocated on chromosome 6p21.33 isa transcriptionfactor of importance in normal inflammatoryand immune responses.NFKBIL1gene regulates thetransduction pathway in immune response, in atherosclerotic plaques and is implicated in the pathogenesis ofatherosclerosis and myocardial infarction (MI).The NFKBIL1 gene isregulated through IkBkinase proteins and any variations in this delicate balance can interfere with normal NFKBIL1 functions. Mutations in the NFKBIL1 gene result in improper functioning oftranscriptionfactor which is associated with increased susceptibility to MI. Hence we studied 100 patients diagnosed with MI and 100 apparently healthy control subjects to identify the mutations in NFKBIL1 gene. The genomicDeoxyribo Nucleic Acid (DNA) was isolated from the MI patients and control subjects and exon 2 active site of NFKBIL1 gene was polymerase chain reaction (PCR) amplified and variations observed in the Single–strand conformation polymorphism (SSCP) gel of PCR products were sequenced. The sequence analysis of exon 2 of NFKBIL1gene showed novel mutations in 4 patientsc.283G>A;p.(Asp95Asn), c.293G>T;p. (Gly98Val), c.323A>G;p.(Gln108Arg) and c.331G>T;p.(Asp111Tyr) respectively. Further, structural analysis showed mutations in exon 2 of NFKBIL1 geneaffects the functioning of ankyrin repeat regions and Adenosine triphosphate (ATP) binding domains,resulting in non–functional NFKBIL1 protein in these patientsand resulting increased risk of MI.