1.A prevalence study of single nucleotide polymorphisms in the promoter of the apolipoprotein E gene in different ethnic groups in Malaysia
Raj Poovindran Anada ; Dharmendra Ganesan ; Nerimala Ramahsamay ; Kum Thong Wong
Neurology Asia 2012;17(4):341-346
Background and Objective: The promoter of the apolipoprotein E (APOE) gene is polymorphic at positions
-491A/T, -427C/T and -219G/T. These single nucleotide polymorphisms may alter transcriptional
activity and impact APOE expression due to differential binding of transcription factors. It has been
suggested that the -491 A, -427 C and -219 T alleles are associated with a high risk of developing
Alzheimer’s disease. This study aims to investigate the frequencies of APOE promoter polymorphisms
in three major ethnic groups (Malay, Chinese and Indian) in Malaysia. Method: DNA was extracted
from blood obtained from 290 healthy people (Malay: n= 92; Chinese: n= 105; and Indian: n= 93),
and the promoter region was amplifi ed using PCR and genotyped by direct sequencing. Result: The
Indian group has the lowest frequencies of - 491 A, - 427 C and - 219 T alleles (83.9%, 3.2% and
56.5%, respectively) compared to the Chinese group with the highest frequencies (97.1%, 11.9% and
67.1%, respectively). The frequencies in the Malay group were somewhere in between (94.6%, 8.2%
and 61.4%, respectively). Moreover, for the - 491 and - 427 positions, the frequencies of possible
genotypes viz., AA or AT or TT and CC or CT or TT, respectively, were statistically signifi cant (P <
0.05, Chi- Square Test) between the 3 ethnic groups.
Conclusion: Based on the frequency of APOE promoter polymorphisms alone, the ethnic Indian may
be predisposed to lower risks for AD than the Chinese or Malay.
2.Cognitive impairments in mild traumatic brain injury apolipoprotein E: A preliminary study in a Level I trauma center
Vigneswaran Veeramuthu ; Devaraj Pancharatnam MSurg ; Anada Raj Poovindran ; Nur Atikah Musthapha ; Wong Kum Thong ; Mazlina Mazlah ; Vicknes Waran ; Dharmendra Ganesan
Neurology Asia 2014;19(1):69-77
The complex pathophysiology of traumatic brain injury, its cascading effects and a varied outcome
suggest that factors such as genetics may permeate and modulate the neurocognitive outcomes
in patients with mild traumatic brain injury (mTBI). This study was conducted to determine the
relationship between genetic polymorphism of apolipoprotein E, and neurocognitive and functional
outcomes in mTBI. Twenty-one patients with mTBI were recruited prospectively. The severity of the
injury was established with the Glasgow Coma Score (GCS). Other assessments included the CT Scan
of the head on admission, Disability Rating Scale, Chessington Occupational Therapy Neurological
Assessment (COTNAB) and Glasgow Outcome Scale (GOS). The Spearmen correlation analysis
of ApoE allele status and the cognitive and functional assessments saw some association with the
Sensory Motor Ability - Coordination (-0.526, p<0.05), Communication Ability (-0.651, p<0.05),
and the Employability (Return to Work) at 1st month (0.455, p<0.05). Notably, the deficits of specific
attributes of visuospatial and sensory motor function were seen with greater impairment consistently
observed in patients with ApoE e4 allele. In conclusion, the preliminary findings support the possible
relationship that exists between ApoE e4 and neurocognitive impairment in mTBI, despite good
functional recovery in 6 months post injury.