Historic, Demographic, and Genetic Evidence for Increased Population Frequencies of CCR5Δ32 Mutation in Croatian Island Isolates after Lethal 15th Century Epidemics

Biloglav, Zrinka; Zgaga, Lina; Smoljanović, Mladen; Hayward, Caroline; Polašek, Ozren; Kolčić, Ivana; Vitart, Véronique; Zemunik, Tatijana; Boraska, Vesna; Torlak, Vesela; Mulić, Rosanda; Ropac, Darko; Grković, Ivica; Rudan, Diana; Ristić, Smiljana; Barbalić, Maja; Campbell, Harry; Wright, Alan F.; Rudan, Igor

doi:10.3325/cmj.2009.50.34

Cited by 13 publications

(12 citation statements)

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“…Vis island sample was genotyped with Illumina HumanHap 300 chip, with a total of 317 503 SNPs, while Korčula and Split samples were genotyped with Human CNV370 chip, containing 346 027 markers (32,(42)(43)(44).…”

Section: Genotypingmentioning

confidence: 99%

Predictive Value of 8 Genetic Loci for Serum Uric Acid Concentration

et al. 2010

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AimTo investigate the value of genomic information in prediction of individual serum uric acid concentrations.Methods Three population samples were investigated: from isolated Adriatic island communities of Vis (n = 980) and Korčula (n = 944), and from general population of the city of Split (n = 507). Serum uric acid concentration was correlated with the genetic risk score based on 8 previously described genes: PDZK1, GCKR, SLC2A9, ABCG2, LR-RC16A, SLC17A1, SLC16A9, and SLC22A12, represented by a total of 16 single-nucleotide polymorphisms (SNP). The data were analyzed using classification and regression tree (CART) and general linear modeling. ResultsThe most important variables for uric acid prediction with CART were genetic risk score in men and age in women. The percent of variance for any single SNP in predicting serum uric acid concentration varied from 0.0%-2.0%. The use of genetic risk score explained 0.1%-2.5% of uric acid variance in men and 3.9%-4.9% in women. The highest percent of variance was obtained when age, sex, and genetic risk score were used as predictors, with a total of 30.9% of variance in pooled analysis. ConclusionDespite overall low percent of explained variance, uric acid seems to be among the most predictive human quantitative traits based on the currently available SNP information. The use of genetic risk scores is a valuable approach in genetic epidemiology and increases the predictability of human quantitative traits based on genomic information compared with single SNP approach. Uric acid is the end product of purine metabolism in humans and higher primates and was initially believed to be a highly potent risk factor for disease development (1). This was confirmed in different studies that reported increased levels of serum uric acid in metabolic disorders and cancer (2-4). However, recent studies have reported possible beneficial effects of uric acid, especially in cardiovascular and neurological diseases of late onset (5,6). Possible protective effects are due to a strong antioxidant properties of uric acid (7). All these findings make uric acid a highly interesting research target in both epidemiology and genetics.Efforts in the search for the genetic basis of uric acid concentrations have been focused on several candidate genes (8,9) and the recently described SLC2A9 has been found to be a gene with a major effect in humans, especially in women (10,11). SLC2A9, also known as Glut 9, is a member of the SLC2A facilitative glucose transporter family, which has an important role in the sugars metabolism (12). The gene encodes a putative transporter of 540 amino acids, which is closely related to several more members of the same gene family, with 44% and 38% resemblance to Glut5 and Glut1, respectively (12). The protein consists of 12 transmembrane domains, sugar motifs, and other signatures which facilitate sugars transport (13). The long form of this protein in humans is most strongly expressed in basolateral membranes of proximal renal tubular cells, the liver, and placenta, w...

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Section: Genotypingmentioning

confidence: 99%

Predictive Value of 8 Genetic Loci for Serum Uric Acid Concentration

et al. 2010

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“…Results of this study should be compared to the neighboring population of Croats where the frequency of the CCR5∆32 allele was found to be 5% (n=1443) and Serbs (n=352) 4.6% [31,32,34,36]. Allele frequency observed in our report was notably higher for the Bosniaks.…”

Section: Discussionmentioning

confidence: 45%

“…The highest allele frequencies are observed among North European populations -for example in Denmark being 12.9% (n=105), Sweden 12.7% (n=1057) and Great Britain 12.3% (n=367), but also a high prevalence of the mutant allele was observed in Slovakia 14.4% (n =335) [4,6,[19][20][21]29,30]. The CCR532 allele frequency among European populations decreases in the Southern Europe being 4.6% in Serbia (n=352), 5.0% in Southeast Mediterranean, Croatia and Italy (n=1443, 1255 respectively) [13,21,[31][32][33][34][35][36][37][38] and 7% in Spain (n=1242) [14,[39][40][41][42][43]. Similar studies conducted from Germany and Poland showed that CCR5Δ32 allele frequency is approximately 10.0% [44][45][46][47][48][49][50][51].…”

Section: Discussionmentioning

confidence: 99%

Frequency of CCR5Δ32 allele in healthy Bosniak population.

Adler¹,

Valjevac²,

Skonieczna-Żydecka³

et al. 2014

Biomol Biomed

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Recent evidence has demonstrated the role of CCR5Δ32 in a variety of human diseases: from infectious and inflammatory diseases to cancer. Several studies have confirmed that genetic variants in chemokine receptor CCR5 gene are correlated with susceptibility and resistance to HIV infection. A 32-nucleotide deletion within the CCR5 reading frame is associated with decreased susceptibility to HIV acquisition and a slower progression to AIDS. Mean frequency of CCR5Δ32 allele in Europe is approximately 10%. The highest allele frequency is observed among Nordic populations (about 12%) and lower in the regions of Southeast Mediterranean (about 5%). Although the frequency of CCR5Δ32 was determined in numerous European populations, there is a lack of studies on this variant in the Bosnia and Hercegovina population. Therefore, the aim of our study was to assess the frequency of CCR5Δ32 allele in the cohort of Bosniaks and compare the results with European reports. CCR5Δ32 was detected by sequence-specific PCR in a sample of 100 healthy subjects from Bosnia and Herzegovina (DNA collected 2011-2013). Mean age of the cohort being 58.8 (± 10.7) years, with 82% of women. We identified 17 heterozygotes and one mutant homozygote in study group, with mean ∆32 allele frequency of 9.5%. CCR5∆32 allele frequency among Bosniaks is comparable to that found in Caucasian populations and follows the pattern of the north-southern gradient observed for Europe. Further studies on larger cohorts with adequate female-to-male ratio are necessary.

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“…Although some scientists have now become skeptical of Y. pestis plague as the causative agent of MBD, many historians, however, still maintain such a causative paradigm (Aberth 2005; Benedictow 2004; Cantor 2001; Hatcher 2008; Horrox 1994; Kelly 2005; Tuchman 1978): Samuel Cohn (2002) appears to be the exception. We are convinced that recently published work identifying (i) MBD as the historical selective pressure that forced up the frequency of the CCR5‐Δ32 allele to present day values observed across Europe (e.g., Biloglav et al 2009; Duncan et al 2005; Stephens et al 1998), (ii) noting that bacteria such as Y. pestis do not use the same CCR5 receptor to penetrate human macrophage and T‐cells (Mecsas et al 2004), and (iii) spatial diffusion velocities of 1–6 km/day (Christakos et al 2005, 2007) strongly suggest a human‐to human etiologic agent for MBD that was quite possibly of viral origin, and not a bacterium such as Y. pestis .…”

Section: Alternative Explanationmentioning

confidence: 59%

Revisiting the Medieval Black Death of 1347–1351: Spatiotemporal Dynamics Suggestive of an Alternate Causation

Welford

Bossak

2010

Geography Compass

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Recent research points to multiple inconsistencies regarding modern Yersinia pestis (in Bubonic, Pneumonic, or Septicemic Plague variants) as a causative agent for the Medieval Black Death (MBD). Published arguments at odds with a Y. pestis‐caused epidemic include differences in recorded periodicity, seasonal mortality peaks, relevant biogeographical details, genetic findings, and spatiotemporal dynamics, among other inconsistencies. Here, we describe and expand on some of the recent literature noting these items. In addition, we discuss preliminary research related to our recently published theory, in which we agree with research suggesting that the MBD was caused by a virus, not a bacterium, and elucidate our contention that seasonal changes and medieval human trade patterns controlled the timing of peak mortality during the MBD and subsequent ‘plagues’. Epidemic evidence from the first epidemic wave and later outbreaks is presented in support of our hypothesis.

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Historic, Demographic, and Genetic Evidence for Increased Population Frequencies of CCR5Δ32 Mutation in Croatian Island Isolates after Lethal 15th Century Epidemics

Abstract: Our results and historical evidence, suggest that the mid-15th century epidemic could have acted as a selection pressure for the CCR5Delta32 mutation.

Cited by 13 publications

References 20 publications

Predictive Value of 8 Genetic Loci for Serum Uric Acid Concentration

Predictive Value of 8 Genetic Loci for Serum Uric Acid Concentration

Frequency of CCR5Δ32 allele in healthy Bosniak population.

Revisiting the Medieval Black Death of 1347–1351: Spatiotemporal Dynamics Suggestive of an Alternate Causation

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