Abstract

Abstract


Objective: To investigate the association of monoamine oxidase Agene polymorphisms with aggression.
Methods: The study was conducted in an ethnic community in Lahore, Pakistan, from August 2008 to December 2009 on the basis of data that was collected through a questionnaire between August 2004 and September 2005. It analysed 10 single nucleotide polymorphisms of monoamine oxidase A in unrelated males from the same ethnic background who were administered a Punjabi translation of the Buss and Perry aggression questionnaire. SPSS 13 was used for statistical analysis.
Results: Of the total 133 haplotypes studied, 52(39%) were Haplotype A, 58(43.6%) B, 8(6%) C, 3(2.3%) D, 9(6.8%) E and 3(2.3%) F. The six haplotypes were analysed for association with scores of the four subscales of the aggression questionnaire and multivariate analysis of variance showed no significant differences (p>0.05 each) in the error variances of the total scores and scores for three of the sub-scales across the haplotypes. The variance was significantly different only for the anger sub-scale (p0.93 in an additional 4(40%) intronic SNPs and in only 2(20%) (rs3027401; rs2205718) of the 10 SNPs there was an appreciably higher (>0.40) frequency of the derived allele. The derived allele frequencies for these two SNPs were higher compared to Africans (AFR) and Europeans (EUR), but lower in comparison with the HapMapGIH samples (Table-2).
The X chromosomal location of the MAOA gene allowed us to determine the haplotype in these male individuals without imputation. The combination of 10 SNPs identified 6 MAOA haplotypes designated A-F here: 52(39%) Haplotype A, 58(43.6%) B, 8(6%) C, 3(2.3%) D, 9(6.8%) E and 3(2.3%) F. Haplotype A was the ancestral haplotype. A median joining network of the 6 haplotypes (Figure-2)showed that two mutational steps separated the two major haplotypes A and B which together comprised 110(83%) of the six variants. All the remaining haplotypes (C-F) were separated by one mutational step.
Haplotypes E was associated with the lowest total mean score of the questionnaire (Figure-2). The derived A allele for SNP rs3027392 that characterises this haplotype is located in the second intron of the MAOA gene. Low mean scores were observed not only for the total scores, but also for the scores across three of the four subscales on the aggression questionnaire (Table-3)for this haplotype but the difference was not significant (p=0.95). The six haplotypes were analysed for association with scores of the four subscales of the aggression questionnaire and MANOVA showed no significant differences (p>0.05 each) in the error variances of the total scores and scores for three of the sub-scales across the haplotypes. The variance was significantly different only for the anger sub-scale (p