Frequency of C3435T polymorphism of MDR1 gene in African people

doi:10.1016/S0140-6736(01)05579-9

The Lancet

Volume 358, Issue 9279, 4 August 2001, Pages 383-384

https://doi.org/10.1016/S0140-6736(01)05579-9 Get rights and content

Summary

The variability of P-glycoprotein expression between individuals is linked to a C3435T polymorphism of the human MDR1 gene. Concentration of P-glycoprotein in intestinal epithelial cells and in a subset of lymphoid cells is substantially lower in people with the T/T genotype than those with the C/C genotype. We compared allele frequencies of the C3435T polymorphism in random samples of west African, African American, white, and Japanese people. We recorded a significantly higher frequency of the C/C genotype in West Africans and African Americans (142 of 172 [83%] and 25 of 41 [61%], respectively), than in white people (139 of 537 [26%]) (p<0·0001). These findings could affect use of drugs that are P-glycoprotein substrates (such as HIV-1 protease inhibitors and ciclosporin) in African populations.

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Hepatitis C virus infectivity and replication efficiency appears to be dependent on the lipid content and organization of the plasma membrane of the host cell, as well as of the intracellular membranous web. As there is increasing awareness of a role played by the efflux pump ABCB1 (p-glycoprotein, P-gp) in lipid homeostasis, its function could be a determinant of chronic HCV infection. The aim of the present study was to examine and compare the distribution of common ABCB1 genotypes in patients with chronic HCV infection (n = 168), hyperlipidemic patients (n = 168) and a control group (n = 173), all from Greece.
Participants were genotyped for the ABCB12677G>T/A and 3435C>T polymorphisms with previously reported PCR-RFLP methods. Genotype and allele frequency distributions were compared between the three groups with the χ² test of independence.
The ABCB1 2677GG (ancestral) genotypes were significantly over-represented in patients with chronic hepatitis C compared to controls (39.3% vs. 26.6%, p = 0.015 according to the dominant model). A similar result was obtained when hyperlipidemic patients were compared to controls (45.2% vs. 26.6%, p < 0.001 according to the dominant model). Comparison of ABCB1 3435C>T genotype and allele distributions provided similar but not as significant differences. Genotype and allele distributions for both ABCB12677G>T/A and 3435C>T were very similar between HCV patients and hyperlipidemic patients.
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Citation Excerpt :
Schaeffeler et al. proved that in healthy persons of West African and African origin living in the USA, the 3435CC genotype incidence is respectively 85% and 61%. Furthermore, they observed that within the white population living in this region the occurrence of 3435CC genotype was as rare as 26% [21]. In the investigated population from Lower Silesia, we also observed lower percentage of 3435CC genotypes (18.81%) within the control group.
In recent years, an increasing incidence of inflammatory bowel disease (IBD) has been reported, mainly as Crohn's disease (CD) and ulcerative colitis (UC). The individual susceptibility, the disease's course and response to the applied therapy is likely due to genetic factors such as ABCB1 gene mutations, exemplified by C3435T polymorphism.
The aim of the study was to evaluate the distribution of C3435T polymorphism regarding the gender in IBD patients and control subjects from Lower Silesia region and its possible association with IBD susceptibility.
The research was conducted in groups of 61 IBD patients and 101 healthy subjects from the Lower Silesia region. Polymorphism of C3435T was determined using PCR-RFLP method.
Frequency distributions of C3435T genotype and of 3435T or 3435C gene alleles of IBD, CD or UC patients were compared to control group; each treated as a whole or split further by gender. The statistically significant correlation was discovered between gender and C3435T genotype both for IBD and CD patients, with 3435CT heterozygote prevailing in IBD and CD males.
Odds ratio calculations revealed statistically significant difference for the 3435CT genotype between control and: IBD group considered as a whole; IBD males; CD males; and for 3435TT variant between control and IBD males. Conclusions. The 3435CT genotype could be a risk factor for IBD and CD in men. The 3435TT genotype in males seems to be associated with the lower chance of IBD presence.
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Research LettersFrequency of C3435T polymorphism of MDR1 gene in African people

Summary

P-glycoprotein: a tangled web waiting to be unraveled. TAG Basic Science Report 2000

Natural selection of hemi- and heterozygotes for G6PD deficiency in Africa by resistance to severe malaria

Nature

Research Letters
Frequency of C3435T polymorphism of MDR1 gene in African people