Is Spatial Distribution of the HIV-1-resistant CCR5Δ32 Allele Formed by Ecological Factors?

Balanovsky, Oleg; Pocheshkhova, Elvira; Pshenichnov, Andrey; Solovieva, Daria; Кузнецова, М. А.; Voronko, O. E.; Churnosov, Mikhail; Tegako, O. V.; Atramentova, L. A.; Lavryashina, M. B.; Evseeva, Irina; Borinska, Svetlana; Boldyreva, M N; Дубова, Надежда; Balanovska, Elena

doi:10.2114/jpa.24.375

Cited by 20 publications

(28 citation statements)

References 17 publications

(35 reference statements)

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“…[7]. In Russians, the frequency of the CCR5del32 allele is appreciably high (10–17% in different regions), whereas the frequency of this allele is equal to 2% in the other group that was studied (Kalmyks).…”

Section: Discussionmentioning

confidence: 99%

Risk of HIV Infection and Lethality Are Decreased in CCR5del32 Heterozygotes: Focus Nosocomial Infection Study and Meta-analysis

et al. 2012

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CCR5del32 Homozygous deletion in the chemokine receptor R5 gene provides almost complete protection to individuals against HIV infection. However, data relating to the protective effect forCCR5del32 heterozygous individuals have been contradictory. The frequency of theCCR5del32allele in population control cohorts was compared with that of a group of children (27 Kalmyks and 50 Russians) infected by G-subtype HIV-1 in a nosocomial outbreak. The frequency of theCCR5del32allele was shown to be lower among the infected children in comparison with that of the control group; however, the difference was small and statistically insignificant. Similar results were obtained in a number of earlier studies. The insignificance of the small differences could be a result of one of two reasons. (i) The fact that there is no protective effect of the heterozygous state, and that the phenomenon depends only on the fluctuation of allele frequencies. In this case, there would be no differences even if the infected cohort is enlarged. (ii)The protective effect of the heterozygous state is real; however, the size of the studied cohort is insufficient to demonstrate it. In order to discern between these two reasons, a meta-analysis of data from 25 published articles (a total of 5,963 HIV-infected individuals and 5,048 individuals in the control group, including the authors’ own data) was undertaken. A conclusion was drawn from the meta-analysis that theCCR5del32 allele protects individuals against the HIV infection even in a heterozygous state (OR=1.22, 95%CI=1.10–1.36). The risk of HIV infection forCCR5 wt/del32 heterozygotes was lower by at least 13% as compared to that for wild typeCCR5 wt/wthomozygotes. Prior to this study, no data of the type or any conclusions had been published for Caucasians. The mortality rate in the 15 years following the infection was found to be approximately 40% lower forCCR5del32 heterozygotes in comparison with that for the wild type homozygotes in the studied group. The size of the studied group was insufficient to claim difference validity (OR=2.0;p= 0.705), even though the effect quantitatively matched the published data. The features of the meta-analysis influencing the threshold level and the statistical validity of the effects are being discussed. The level of theCCR5del32 protective effect on the chances to be infected with HIV and on the outcome of the HIV infection was assessed for various ethnic groups.

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Section: Discussionmentioning

confidence: 99%

Risk of HIV Infection and Lethality Are Decreased in CCR5del32 Heterozygotes: Focus Nosocomial Infection Study and Meta-analysis

et al. 2012

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“…The frequency decreases from north to south throughout Europe, although there are pockets of high frequency in the northern coasts of France and parts of Russia (Balanovsky et al, 2005). The frequency decreases from north to south throughout Europe, although there are pockets of high frequency in the northern coasts of France and parts of Russia (Balanovsky et al, 2005).…”

Section: Why Does the Ccr5-δ32 Allele Reach Such High Frequencies In mentioning

confidence: 91%

Coevolution of Humans and Pathogens

Sattenspiel

2015

Basics in Human Evolution

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“…Libert et al (4) hypothesized that the allele originated in Northeastern Europe and spread towards the south of the continent. An alternative assumption came from Bala novsky et al who suggested that the allele emerged among Uralic-speaking populations and that its frequency increased in Northeastern Europe as a result of positive selection and/or genetic drift (5). According to this group, secondary spread and selection occurred due to gene flow and migrations.…”

Section: Introductionmentioning

confidence: 99%

“…Although individuals homozygous for CCR5D32 show no obvious immunodeficiency, it has recently been reported that this allele is a risk factor for both early and late clinical manifestations of the West Nile virus infection (15,16). Alternatively, there are hypotheses that the frequency of CCR5D32 has been influenced by climatic or geographical factors (5,17).…”

Section: Introductionmentioning

confidence: 99%

The Frequency of Allele CCR5∆32 in a Serbian Population / UČESTALOST ALELA CCR5∆32 U SRPSKOJ POPULACIJI

Đorđević¹,

Timotijević²,

Pruner³

et al. 2013

Journal of Medical Biochemistry

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SummaryBackground: The mutant CCR5D32 allele confers resistance to HIV infection. Several hypotheses regarding its origin and persistence in the human population have been proposed. It is assumed that the D32 mutation was introduced in Northern or Eastern Europe and that it spread to the south. Although the frequency of CCR5D32 was determined in numerous European nations and regions, further data are needed to complete the puzzle of CCR5D32 distribution within the continent. Methods: To this end, CCR5D32 frequency was determined in a Serbian population (sample size 352). DNA was extracted from peripheral whole blood and polymerase chain reaction specific for CCR5 gene was performed. A reaction product of 263 bp was obtained from the wild--type CCR5 sequence and a product of 231 bp was obtain ed from the truncated CCR5D32 sequence. Results: Overall allele frequency of CCR5D32 is 4.55%; 0.57% of individuals in the examined population are homozygous and 8.52% are heterozygous for CCR5D32. Conclusions: The determined frequency of the CCR5D32 allele in a Serbian population is unexpectedly low, consi dering ethnically related populations.

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Is Spatial Distribution of the HIV-1-resistant CCR5Δ32 Allele Formed by Ecological Factors?

Cited by 20 publications

References 17 publications

Risk of HIV Infection and Lethality Are Decreased in CCR5del32 Heterozygotes: Focus Nosocomial Infection Study and Meta-analysis

Risk of HIV Infection and Lethality Are Decreased in CCR5del32 Heterozygotes: Focus Nosocomial Infection Study and Meta-analysis

Coevolution of Humans and Pathogens

The Frequency of Allele CCR5∆32 in a Serbian Population / UČESTALOST ALELA CCR5∆32 U SRPSKOJ POPULACIJI

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