Analysis of TPI gene promoter variation in three sub‐Saharan Africa population samples

Abstract

Population samples from Angola, Mozambique, and S. Tomé e Príncipe were screened for the TPI gene promoter variants -5A?G, -8G?A and -24T?G. Three haplotypes were identified in the three populations: the haplotype -5A-8G-24T (average frequency 65.3%) and two less common haplotypes -5G-8G-24T (average frequency 24.7%) and -5G-8A-24T (average frequency 10.0%). A population sample from Central Portugal showed the haplotype -5A-8G-24T in 139 chromosomes and one subject heterozygous for haplotype -5G-8A-24G. The exact test of sample differentiation among three groups of malaria-infected individuals classified according to the severity of the disease showed no significant differences. We confirmed TPI gene diversity in sub-Saharan Africa, but we could not detect any association between TPI promoter variation and a malarial protective effect. Larger scale epidemiological studies are thus required to clarify this putative mechanism of natural host defense against this worldwide public health problem. Am. J. Hum.

Triosephosphate isomerase gene promoter variation: -5G/A and -8G/A polymorphisms in clinical malaria groups in two African populations

“…Due to the major public health problem that malaria continues to be, to find potential new targets for new antimalarial therapeutics, such as the inhibition of metabolic pathways or enzymes necessary to parasite survival, is an urgent need. Individuals from Angola and Mozambique present 47% and 53% of genotypes with TPI1 promoter variants, respectively, which are consistent with those previously described by Humphries et al (1999a) and Manco et al (2009) for the African population.…”

“…These data are supported by the elevated intra-allelic variation of CD4 and ATN1 loci. Despite this, among non-African populations, the allelic distribution of -5A is very similar to the African population (Humphries et al, 1999a;Manco et al, 2009).…”

“…However, while the -5G minor allele has global geographical distribution and has attained high frequency in African, Caribbean and Oriental populations, the -8A minor allele had been found in geographically dispersed populations, being more frequent in individuals of African origin (Humphries et al, 1999a;Manco et al, 2009). Humphries et al (1999a) reported that -5G and associated haplotypes were found to be in linkage disequilibrium (LD) with an intragenic polymorphism at nucleotide 2262 in intron 5 (Arya et al, 1997), which could be indicative of a common ancestral origin.…”

Change of TATA-binding protein affinity to oligonucleotides corresponding to TATA boxes in human gene promoters bearing polymorphisms associated with hereditary diseases

“…The TPI gene is located on the 12th chromosome, consists of seven exons and six introns (Valentin et al, 2000), is expressed in all types of tissues, and is a household gene (Brown et al, 1985;Watanabe et al, 1996;Manco et al, 2009). The catalytically active form of TPI is a homodimer consisting of two subunits with a molecular mass of 27 kDa (Orosz et al, 2006 in GC dinucleotides.…”