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Genetic variation in proteins: comparison of one-dimensional and two-dimensional gel electrophoresis.

Two proteins with known characteristics on one-dimensional gels were studied by two-dimensional electrophoresis to compare the sensitivities of the two methods in detecting genetic variation. Two-dimensional electrophoresis was found to be less sensitive than several types of one-dimensional gels in distinguishing variants of both proteins. Denaturation of proteins in urea in the two-dimensional method makes it possible to distinguish closely related proteins that differ from each other by units of charge. Many more types of variation in protein sequences can be distinguished on one-dimensional gels in the absence of denaturants. The estimates of heterozygosity based on two-dimensional gels are lower than those based on other methods, at least in part, because of the limited types of sequence differences that can be detected on two-dimensional gels. The application of two-dimensional electrophoresis to the measurement of genetic variation and to the detection of new mutations should be made carefully, in view of the limited sensitivity of the method in finding differences in sequence.

Animals↗

Population differentiation and genetic variation in host choice among pea aphids from eight host plant genera.

Habitat choice plays a critical role in the processes of host range evolution, specialization, and ecological speciation. Pea aphid, Acyrthosiphon pisum, populations from alfalfa and red clover in eastern North America are known to be genetically differentiated and show genetic preferences for the appropriate host plant. This species feeds on many more hosts, and here we report a study of the genetic variation in host plant preference within and between pea aphid populations collected from eight genera of host plants in southeastern England. Most host-associated populations show a strong, genetically based preference for the host plant from which they were collected. Only in one case (populations from Vicia and Trifolium) was there little difference in the plant preference spectrum between populations. All populations showed a significant secondary preference for the plant on which all the aphid lines were reared: broad bean, Vicia faba, previously suggested to be a "universal host" for pea aphids. Of the total genetic variance in host preference within our sample, 61% could be attributed to preference for the collection host plant and a further 9% to systematic differences in secondary preferences with the residual representing within-population genetic variation between clones. We discuss how a combination of host plant preference and mating on the host plant may promote local adaptation and possibly ecological speciation, and whether a widely accepted host could oppose speciation by mediating gene flow between different populations.

Animals↗

Common genetic variation in the sex steroid hormone-binding globulin (SHBG) gene and circulating shbg levels among postmenopausal women: the Multiethnic Cohort.

SHBG transports sex steroid hormones in the blood, and levels in humans are thought to partially be genetically determined. Recently, studies have found a pentanucleotide (TAAAA)n repeat polymorphism in the promoter of the SHBG gene and a missense polymorphism in exon 6 (Asp327Asn) to predict circulating SHBG levels. Based on the potential role of common genetic variation in SHBG to serve as a marker of SHBG levels in the general population, we evaluated the association between the (TAAAA)n repeat polymorphism, Asp327Asn polymorphism, and SHBG levels in a population of African-American, Native Hawaiian, Japanese, Latina, and white healthy postmenopausal women from the Multiethnic Cohort Study (n = 372). Mean SHBG levels were not significantly different between carriers and noncarriers of the Asn327 allele [minor allele frequency range across ethnic groups, 0.02-0.14; Asp/Asn and Asn/Asn genotypes, 33.6 mol/liter; 95% confidence interval (CI), 28.2-40.0; n = 49; Asp/Asp genotype, 30.8 mol/liter (95% CI, 28.7-33.1; n = 296); P = 0.37]. For the repeat polymorphism, we observed six different SHBG repeat alleles segregating in the population (TAAAA6-11), and the distribution of these alleles varied widely across populations. We found suggestive evidence of linkage disequilibrium between the Asn327 allele and the eight-repeat allele in all populations except African-Americans (P > or = 0.08). In analysis of the repeat polymorphism, SHBG levels among carriers of two short alleles (seven or fewer repeats; 31.2 nmol/liter; 95% CI, 27.3-35.6; n = 82) were not statistically different from those of carriers of two long alleles (more than seven repeats; 32.7 nmol/liter; 95% CI, 29.4-36.3; n = 124; P = 0.59). We did, however, observe individual genotypic classes (n = 16) to contribute modestly to the overall prediction of SHBG levels (by analysis of covariance, P = 0.03). Carriers of the six-repeat allele (27.9 nmol/liter; 95% CI, 25.2-30.8; n = 147) were found to have nominally significantly lower SHBG levels than noncarriers (32.4 nmol/liter; 95% CI, 29.7-35.2; n = 202; P = 0.03). This effect was stronger among the subset of women who also carried the Asn327 allele (interaction, P = 0.006). In summary, these results suggest that genetic variation at the SHBG locus may contribute to modest differences in SHBG levels among healthy postmenopausal women, and that much larger studies will be needed to better comprehend the effects of common variations at this locus in predicting circulating SHBG levels.

Aged↗

Genetic variation within and relationships among populations of Asian water buffalo (Bubalus bubalis).

Genetic variation at 53 protein-coding loci (25 polymorphic) was analysed for 17 water buffalo populations-12 swamp, three Lankan and two of the Murrah breed (river type), to determine the magnitude of genetic differentiation and the genetic relationships among the populations. In accord with previous cytological studies, the Lankan buffalo clearly are river type. Significant deviations from Hardy-Weinberg equilibrium were shown for a number of locus-population combinations, with all populations but one showing significant heterogeneity in these deviations among loci. By contrast, heterogeneity among populations for each locus was much less, indicating locus-specific deviations, which suggest selection affecting allele frequencies at some loci. There was significant genetic differentiation among populations of both the swamp and river types. The differentiation among the swamp populations may reflect the geography of south-east Asia and the presumed spread of the swamp buffalo through this region. Phylogenies derived from pairwise genetic distance estimates show the clear separation of swamp and river types, but the topology of the swamp populations shows rather poor consistency with their geographic locations. For at least one population (Australia), it is clear that bottleneck effects have distorted the phylogenetic topology. Average genetic distances for both the swamp and river types, as compared with previous studies of livestock breeds, show that the genetic differentiation of each of these sets of populations is of the same order of magnitude as that among well-recognized and established breeds of other species.

Animals↗

Genetic variations of cell wall digestibility related traits in floral stems of Arabidopsis thaliana accessions as a basis for the improvement of the feeding value in maize and forage plants.

Floral stems of Arabidopsis thaliana accessions were used as a model system relative to forage plant stems in genetic variation studies of lignin content and cell wall digestibility related traits. Successive investigations were developed in a core collection of 24 Arabidopsis accessions and in a larger collection of 280 accessions. Significant genetic variation for lignin content in the cell wall, and for the two in vitro cell wall digestibility investigated traits, were found both in the core collection and in the large collection. Genotype x environment interactions, investigated in the core collection, were significant with a few genotypes contributing greatly to interactions, based on ecovalence value estimates. In the core collection, genotypes 42AV, 224AV, and 8AV had low cell wall digestibility values, whatever be the environmental conditions. Genotype 157AV, observed only in one environment, also appeared to have a low cell wall digestibility. Conversely, genotypes 236AV, 162AV, 70AV, 101AV, 83AV had high cell wall digestibility values, genotype 83AV having a slightly greater instability across differing environments than others. The well-known accession Col-0 (186AV) appeared with a medium level of cell wall digestibility and a weak to medium level of interaction between environments. The ranges of variation in cell wall digestibility traits were higher in the large collection than in the core collection of 24 accessions, these results needing confirmation due to the lower number of replicates. Accessions 295AV, 148AV, and 309AV could be models for low stem cell wall digestibility values, with variable lignin content. Similarly, accessions 83AV and 162AV, already identified from the study of the core collection, and five accessions (6AV, 20AV, 91AV, 114AV, and 223AV) could be models for high stem cell wall digestibility values. The large variations observed between Arabidopsis accessions for both lignin content and cell wall digestibility in floral stems have strengthened the use this species as a powerful tool for discovering genes involved in cell wall biosynthesis and lignification of dicotyledons forage plants. Investigations of this kind might also be applicable to monocotyledons forage plants due to the basic similarity of the genes involved in the lignin pathway of Angiosperms and the partial homology of the cell wall composition and organization of the mature vascular system in grasses and Arabidopsis.

Animal Feed↗

Genetic variation in apolipoprotein H (beta2-glycoprotein I) affects the occurrence of antiphospholipid antibodies and apolipoprotein H concentrations in systemic lupus erythematosus.

Apolipoprotein H (apoH, protein; APOH, gene) is a required cofactor for the production of antiphospholipid antibodies (APA). In this study we have examined whether genetic variation in the APOH gene affects variation in risk for systemic lupus erythematosus (SLE), occurrence of antiphospholipid antibodies (APA), anti-apoH, and plasma apoH concentrations. A total of 222 white SLE women were screened for four APOH polymorphisms (codons 88, 247, 306, and 316) by polymerase chain reaction, and for plasma apoH concentrations by ELISA. Of these, 29.3% were positive for APA (APA-positive group) and 31.1% for anti-apoH. None of the four APOH polymorphisms were significantly associated with variation in risk for SLE. The codons 306 and 316 polymorphisms showed significant, gene-dosage effects on plasma apoH concentrations (P<0.0001) and explained 30% and 13%, respectively, of the residual variation in apoH concentrations. No significant association was observed between anti-apoH status and APOH polymorphisms or plasma apoH levels. However, plasma apoH concentrations were significantly higher in patients positive for APA than in patients negative for APA (18.5+/-4.0 mg/dl vs 17.1+/-3. 8 mg/dl; P=0.02). The distribution of the Trp316Ser polymorphism was significantly different between the APA-positive and APA-negative groups. The frequency of the mutant allele (Ser316) was significantly lower in the APA-positive group than the APA-negative group (3.1% vs 12.1% P<0.04), indicating that the Ser316 mutation is protective against the production of phospholipid-apoH dependent APA. Our data indicate that common genetic variation in the APOH gene is a significant determinant of plasma apoH variation in SLE patients, and the Trp316Ser polymorphism appears to provide protection against the production of APA in SLE patients.

Adult↗

Molecular genetic variation and individual survival during population crashes of an unmanaged ungulate population.

Theoretical models of the effect of population bottlenecks on genetic variation assume that individuals are removed at random from the population. We investigated this assumption in a naturally regulated, unstable population of Soay sheep (Ovis aries). During rapid population declines or 'crashes', individuals were not removed at random with respect to genotype: we found associations between individual survival and certain genotypes at five polymorphic protein or microsatellite DNA loci (Ada, Got, Tf, MAF18 and OPACAP). Some loci appeared to show simple associations with survival whereas others had more complex interactions with crash year or age: all displayed different patterns of association between the sexes. Simple overdominance was not a general feature of our data; it seems likely that fluctuating selecting, countervailing selection in different fitness components or frequency-dependent selection may explain the pattern and complexity of the associations shown at different loci. Our study cannot distinguish between selection acting at these loci or at other, closely linked loci. However, our empirical study implies that the molecular genetic outcome of population bottlenecks in natural populations does not always follow theoretical expectations based on the random removal of genotypes. Bottlenecks in which individuals are removed at random are distinct from bottlenecks in which there is scope for selection via non-random survival of individuals.

Alleles↗

Genetic variation of human UDP-glucuronosyltransferase: implications in disease and drug glucuronidation.

The uridine diphosphate (UDP)-glucuronosyltransferases (UGTs) are key enzymes in human detoxication of xeno- and endobiotics. Potentially toxic endogenous compounds such as bilirubin, or exogenous compounds such as drugs, pesticides, and carcinogens, are generally transformed into water-soluble glucuronides for excretion in bile and urine. The UGTs are encoded by a multigene family in humans. A relatively small number of human enzymes catalyze the glucuronidation of thousands of compounds. Genetic variations and single nucleotide polymorphisms (SNPs) within the UGT genes are remarkably common, and lead to genetic polymorphisms. The multiplicity of transferases, some exhibiting overlapping substrate specificity, may provide functional compensation for genetic deficit in some cases. Genetic variation may cause different phenotypes by affecting expression levels or activities of individual UGTs. This inter-individual variation in UGTs has resulted in functional deficit affecting endogenous metabolism and leading to jaundice and other diseases. Disruption of the normal metabolic physiology, by the reduction of bile acid excretion or steroid glucuronidation, may lead to cholestasis and organ dysfunction. Deficient glucuronidation of drugs and xenobiotics have an important pharmacological impact, which may lead to drug-induced adverse reactions, and even cancer. Additional novel polymorphisms in this gene family are yet to be revealed and studied, but will have a profound effect on the development of new drugs and therapies.

Animals↗

Haplotypes and the systematic analysis of genetic variation in genes and genomes.

Haplotypes have been used in various fields of genetics for a long time, in a variety of contexts, and for different purposes. Now, haplotype-based approaches to the analysis of candidate genes and genome-wide linkage disequilibrium (LD) mapping have gained center stage. It is time to explicitly distinguish the different concepts implied in the present haplotype approaches: haplotypes are not haplotypes, after all. The distinction of three different categories, ancestral, common haplotypes or haplotype blocks, gene-based haplotypes as complex genetic markers and gene-based functional haplotypes, is proposed. These categories serve as framework to review and analyze in particular the recent work suggesting evidence for a haplotype block structure of the human genome and the body of comparative sequencing studies addressing haplotype and LD structures at the gene level. Haplotype approaches will be evaluated along the dimensions preselection of variants versus complete DNA sequence information, role of LD and stages in the process of disease gene identification. Overall, the content of haplotypes is conceived as a function of available technologies to evaluate genetic variation and general advances in human genome research.

Genetic Predisposition to Disease↗

Genetic variation of broiler feed consumption and efficiency corrected for differences in test body weights.

Feed consumption and feed efficiency data obtained over nine generations from three selected strains of broilers were adjusted for differences in either initial or initial and final test BW (at 28 and 42 d, respectively). Genetic and environmental variables were estimated for each strain using an animal model with restricted maximum likelihood procedures to avoid bias due to reduced genetic variation caused by selection. Variance component and heritability estimates before and after adjustment of these traits for differences in test weights were evaluated. Adjustments of feed consumption data for either initial test BW or both initial and final test BW reduced additive genetic and environmental variation. Reductions were relatively greater for additive genetic than for environmental variance, thereby reducing the heritability of the adjusted trait. Adjustment of feed efficiency for initial test BW altered additive genetic variation little and reduced environmental variation slightly; however, correction for both test BW reduced variation of both components. Heritability of adjusted feed efficiency was 40% larger (.33 to .35 vs .21 to .28) than for uncorrected feed efficiency, but phenotypic variation of the adjusted feed efficiency was reduced 42% (5.82 to 6.13 vs 10.30 to 11.35). Heritabilities of feed consumption and efficiency were essentially the same (.34 and .36) after adjustment for both test weights. Changes in genetic and environmental variation and heritability due to adjustments were similar for the three strains.

Animals↗

Genetic variation in geographically isolated populations and subspecies of Oncomelania hupensis determined by a PCR-based RFLP method.

Previously, the species complex Oncomelania hupensis, individuals of which act as intermediate hosts for the human bloodfluke Schistosoma japonicum, has been characterised by morphological and isoenzyme criteria. We have examined genetic variation between and within three subspecies of Oncomelania hupensis, i.e. O. h. hupensis (China), O. h. quadrasi (Philippines) and O. h. nosophora (Japan), by direct means using a PCR-based RFLP method. The subspecies of O. hupensis were readily distinguished by their characteristic restriction patterns, supporting isoenzyme data which suggests these may warrant species-specific status. No genetic variation was observed between O. h. quadrasi from different islands within the Philippines. In contrast, geographical isolates of O. h. hupensis differed markedly by this method indicating several genetically distinct populations of O. h. hupensis occur in China.

Animals↗

Genetic variation in low-dose UV-induced suppression of contact hypersensitivity and in the skin photocarcinogenesis response.

Two of the major cutaneous consequences of ultraviolet (UV) radiation exposure are immunosuppression and the development of skin cancer. This study examined whether these effects are genetically determined. Suppression of contact hypersensitivity by local, low-dose UV radiation was examined in what have been termed "UV-susceptible" and "UV-resistant" strains of mice. C3H/HeJ mice ("UV resistant") were resistant to the adverse effects of low-dose UV radiation when normal doses of hapten were applied to UV-irradiated skin; however, they were sensitive when the amount of hapten used for sensitization was reduced. A similar effect was observed in BALB/c mice ("UV resistant") and when the hapten was dimethylbenz(a)anthracene, thus indicating that the genetic variation was not strain or hapten specific. Despite the fact that some strains were sensitive and some were resistant to low-dose UV radiation when high doses of hapten were employed, all strains initially sensitized to hapten through UV-irradiated skin were found to be unresponsive when rechallenged on normal skin, no matter what the initial sensitizing dose of hapten was. To determine whether other biologic effects of UV also exhibited genetic variation, C3H/HeN and C3H/HeJ mice were compared for susceptibility to UVB-induced skin cancer formation. C3H/HeJ mice developed significantly more tumors than C3H/HeN mice when subjected to a single dose of UV radiation followed by repeated exposure to the tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate. These studies provide strong evidence that genetic factors influence individual susceptibility to the biologic effects of UV radiation.

Animals↗

Patterns of genetic variation in Phialocephala fortinii across a broad latitudinal transect in Canada.

Dark septate root endophytes (DSE) are an artificial assemblage of fungi that have darkly pigmented, septate hyphae and that are frequent or distinctive intracellular associates of roots of apparently healthy plants. Based on isolates obtained from the roots of Salix spp., the distribution of a common DSE fungus, Phialocephala fortinii, was examined along a latitudinal transect in Canada running from the high arctic to the 49 degrees N parallel. Non-sporulating isolates were provisionally identified as P. fortinii through analysis of DNA sequence data of the ITS2 region of rDNA. P. fortinii was isolated frequently from boreal and arctic habitats, but rarely from grassland habitats. Patterns of genetic variation were examined through analysis of amplified fragment length polymorphisms (AFLP). All AFLP profiles were unique with the majority of genetic variation occurring among individuals within the collecting sites at each latitude. Neighbour-joining analysis of genetic distances yielded eight well-supported clusters, three of which included individuals from more than one latitude. Some linkage disequilibrium, possibly due to partial clonality, was detected.

Ascomycota↗

Heat induced male sterility in Drosophila melanogaster: adaptive genetic variations among geographic populations and role of the Y chromosome.

We analyzed genetic variation among geographically diverse populations of Drosophila and showed that tropical flies are more tolerant than temperate ones to heat-induced male sterility, as assessed by the presence of both motile sperm and progeny production. In tropical populations, the temperature inducing 50% sterility (median threshold) is 1 degrees C above the value for temperate populations (30.4 vs. 29.4 degrees C). When transferred to a mild permissive temperature (21 degrees C), males recover fertility. Recovery time is proportional to pre-adult culture temperature. At these temperatures, recovery time is greater for temperate than for tropical populations. Crosses between a temperate and a tropical strain (F1, F2 and successive backcrosses) revealed that the Y chromosome was responsible for much of the geographic variation. Sterile males exhibited diverse abnormalities in the shape and position of sperm nuclei. However, impairment of the spermatid elongation seems to be the major factor responsible for sperm inviability. Heat-induced male sterility seems to be quite a general phenomenon in Drosophilid species and variation of threshold temperatures may be important for explaining their geographic distributions.

Adaptation, Physiological↗

Genetic variation for egg production, egg quality and bone strength in selected and traditional breeds of laying fowl.

1. A multi-breed experiment was conducted with 25 commercial and traditional lines of laying fowl to determine the extent of between-breed genetic variation for adult body weight, sexual maturity, rate of lay, egg weight and egg composition to 55 weeks of age. The genetic variability for bone strength and eggshell strength was determined at 55 weeks of age and a comparison of commercially selected and traditional breeds was performed. 2. The proportion of the total variation that was associated with breed or line of origin was high (> 0.8) for body weight, sexual maturity and shell colour; moderately high (0.4 to 0.7) for rate of lay, early and late egg weight, weights of egg yolk, albumen and shell at 55 weeks; and low (< 0.4) for egg weight at 42 to 45 weeks, albumen quality and the number of egg inclusions. 3. There were no detectable differences between breed within category (traditional and commercial lines) for rate of lay, and estimates of breed variation for egg weight and egg components were substantially decreased within category compared with the overall analysis. 4. Commercial lines displayed earlier sexual maturity, greater rates and persistency of lay, and higher egg weights at earlier (32 to 35 weeks) and later (52 to 55 weeks) ages. At 55 weeks, the larger eggs from commercial birds contained more albumen of higher quality and paler yolks of similar weight to those from traditional breeds. The relative weight of the eggshell was similar in both categories. 5. There was considerable genetic variation between commercial lines for bone density and a moderate proportion of genetic variability for bone strength. Commercial lines had very weak bones compared with traditional lines but there was relatively little genetic variation for eggshell strength. The results suggest that eggshell quality is maintained in genetically selected lines at the expense of bone strength and bone radiographic density.

Animals↗

Genetic variation of dTDP-L-rhamnose pathway genes in Salmonella enterica.

The genetic variation in the dTDP-L-rhamnose pathway gene set (rmlB, rmlD, rmlA, rmlC) in Salmonella enterica was examined after sequencing the four genes from 11 rml-containing gene clusters encoding seven O antigens, and a 903 bp rmlB segment from another 23 strains representing the seven subspecies. There was considerable sequence variation and strong polarity in the nature and level of variation among rml genes. The 5' end of the rml gene set, including rmlB, rmlD and most of rmlA, is in general subspecies specific. In contrast, the 3' end, including part of rmlA and all of rmlC, is O antigen specific. The G+C content of the 3' end is lower than that of the 5' end. The variation in the 3' end of the gene set is much greater than that of the 5' end. It is apparent that the rml gene set of S. enterica includes genes with two different evolutionary histories. In addition, there has been extensive recombination in the gene set, probably related to O antigen transfer between subspecies. These findings provide evidence for the lateral transfer of O antigen genes between species and among subspecies of S. enterica. The results have also shown that conserved genes at the end of an O antigen gene cluster play a major role in mediating exchange of the central serogroup-specific regions.

Bacterial Proteins↗

Genetic variation in two conserved local Romanian pig breeds using type 1 DNA markers.

Analysis of the genetic variation of an endangered population is an important component for the success of conservation. Animals from two local Romanian pig breeds, the Mangalitsa and Bazna, were analysed for variation at a number of genetic loci using PCR-based DNA tests. Polymorphism was assessed at loci which 1) are known to cause phenotypic variation, 2) are potentially involved in trait differences or 3) are putative candidate genes. The traits considered are disease resistance, growth, coat colour, meat quality and prolificacy. Even though the populations are small and the markers are limited to specific genes, we found significant differences in five of the ten characterised loci. In some cases the observed allele frequencies were interesting in relation to gene function and the phenotype of the breed. These breeds are part of a conservation programme in Romania and marker information may be useful in preserving a representative gene pool in the populations. The use of polymorphisms in type 1 (gene) markers may be a useful complement to analysis based on anonymous markers.

Animals↗

Genetic variation at the interleukin-1 locus is a determinant of changes in soluble endothelial factors in patients with acute coronary syndromes.

Acute coronary syndromes (ACSs) are associated with both systemic inflammatory activation and endothelial cell activation, and both of these are linked to patient outcome. Genetic variation at the interleukin-1 (IL-1) locus influences the clinical patterns of inflammatory disease. We therefore examined the association between IL-1 gene polymorphisms and levels of systemic inflammatory activation markers [C-reactive protein (CRP) and IL-1 receptor antagonist (IL-1ra)] and of soluble endothelial activation markers [von Willebrand factor (vWF) and E-selectin], in a cohort of 63 patients presenting with non-ST-elevation ACS. The IL-1 locus did not significantly influence any of the markers studied at 24 h after presentation. Associations of IL-1 polymorphisms with the changes (Delta) in CRP, IL-1ra, E-selectin and vWF levels between 24 and 48 h were examined in later studies. Delta CRP and Delta IL-1ra showed no significant association with any of the polymorphisms studied. There was a strong association between carriage of the rare allele (allele 2) of the intron 2 variable number of tandem repeats polymorphism of IL-1RN (designated IL-1RN*2) and Delta E-selectin levels: [carriage of *2, 3.03 ng/ml [95% confidence interval (CI) 6.26 to 1.51 ng/ml]; non-carriage of *2, 0.12 ng/ml (95% CI 1.07 to -1.76 ng/ml); P=0.0016], and also between carriage of IL-1RN*2 and Delta vWF levels [carriage of *2, 0.78 i.u./ml (95% CI 0.96 to 0.44 i.u./ml); non-carriage of *2, 0.1 i.u./ml (95% CI 0.19 to -0.1 i.u./ml); P=0.0003]. A composite analysis consisting of carriage of IL-1RN*2 and the genotype at position -511 in the IL-1B gene suggests the existence of haplotypes that influence Delta vWF and Delta E-selectin in patients with ACS. Carriage of IL-1RN*2 was also associated with a 2-fold increased likelihood of a troponin-positive status compared with non-carriage (P=0.0385). These data indicate that, in the setting of non-ST-elevation ACS, genetic variation at the IL-1 gene locus contributes to the changes in soluble markers of endothelial inflammation.

ABO Blood-Group System↗