| 1. |
- Sarwar, Nadeem, et al.
(författare)
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Interleukin-6 receptor pathways in coronary heart disease : a collaborative meta-analysis of 82 studies
- 2012
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Ingår i: The Lancet. - New York, NY, USA : Elsevier. - 0140-6736 .- 1474-547X. ; 379:9822, s. 1205-1213
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Tidskriftsartikel (refereegranskat)abstract
- Background: Persistent inflammation has been proposed to contribute to various stages in the pathogenesis of cardiovascular disease. Interleukin-6 receptor (IL6R) signalling propagates downstream inflammation cascades. To assess whether this pathway is causally relevant to coronary heart disease, we studied a functional genetic variant known to affect IL6R signalling. Methods: In a collaborative meta-analysis, we studied Asp358Ala (rs2228145) in IL6R in relation to a panel of conventional risk factors and inflammation biomarkers in 125 222 participants. We also compared the frequency of Asp358Ala in 51 441 patients with coronary heart disease and in 136 226 controls. To gain insight into possible mechanisms, we assessed Asp358Ala in relation to localised gene expression and to postlipopolysaccharide stimulation of interleukin 6. Findings: The minor allele frequency of Asp358Ala was 39%. Asp358Ala was not associated with lipid concentrations, blood pressure, adiposity, dysglycaemia, or smoking (p value for association per minor allele >= 0.04 for each). By contrast, for every copy of 358Ala inherited, mean concentration of IL6R increased by 34.3% (95% CI 30.4-38.2) and of interleukin 6 by 14.6% (10.7-18.4), and mean concentration of C-reactive protein was reduced by 7.5% (5.9-9.1) and of fibrinogen by 1.0% (0.7-1.3). For every copy of 358Ala inherited, risk of coronary heart disease was reduced by 3.4% (1.8-5.0). Asp358Ala was not related to IL6R mRNA levels or interleukin-6 production in monocytes. Interpretation: Large-scale human genetic and biomarker data are consistent with a causal association between IL6R-related pathways and coronary heart disease.
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| 2. |
- Adamovic, Svetlana, 1965, et al.
(författare)
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Fine mapping study in Scandinavian families suggests association between coeliac disease and haplotypes in chromosome region 5q32.
- 2008
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Ingår i: Tissue Antigens. - : Wiley. - 1399-0039 .- 0001-2815. ; 71:1, s. 27-34
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Tidskriftsartikel (refereegranskat)abstract
- The previous genome-wide scan in Scandinavian families supported earlier evidence for linkage of a region on chromosome 5 (5q31–33) to coeliac disease. This study deals with further genetic mapping of an 18 cM region, spanning from marker GAh18A (131.87 Mb) to D5S640 (149.96 Mb). Linkage and association analyses were performed in a two-step approach. First, seven microsatellites were added. Strong evidence for linkage was obtained with a Zlr score of 3.96, Pnc = 4 × 10−5 at marker D5S436. The strongest association was with a haplotype consisting of the markers D5S2033 and D5S2490 (Pnc < 0.001). In the second step, we added 17 microsatellites and 69 single nucleotide polymorphisms (SNPs) to the analysis. These markers were located close to or within candidate genes across the region of approximately 7 Mb beneath the linkage peak marked by D5S2017 and D5S812. A substantial increase of the linkage signal with a maximum Zlr score of 4.6 at marker rs1972644 (Pnc = 2 × 10−6) was obtained and several SNPs showed association. Seven SNPs that individually showed the strongest association were genotyped in a second independent family sample set (225 trios). In the trio family sample as well as in the multiplex family sample, the strongest association was found with SNPs within the region flanked by the associated microsatellites D5S2033 and D5S2490 at 5q32.
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| 3. |
- Jiao, Xiang, et al.
(författare)
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PHIP - a novel candidate breast cancer susceptibility locus on 6q14.1
- 2017
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Ingår i: Oncotarget. - : IMPACT JOURNALS LLC. - 1949-2553. ; 8:61, s. 102769-102782
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Tidskriftsartikel (refereegranskat)abstract
- Most non-BRCA1/2 breast cancer families have no identified genetic cause. We used linkage and haplotype analyses in familial and sporadic breast cancer cases to identify a susceptibility locus on chromosome 6q. Two independent genome-wide linkage analysis studies suggested a 3 Mb locus on chromosome 6q and two unrelated Swedish families with a LOD > 2 together seemed to share a haplotype in 6q14.1. We hypothesized that this region harbored a rare high-risk founder allele contributing to breast cancer in these two families. Sequencing of DNA and RNA from the two families did not detect any pathogenic mutations. Finally, 29 SNPs in the region were analyzed in 44,214 cases and 43,532 controls from BCAC, and the original haplotypes in the two families were suggested as low-risk alleles for European and Swedish women specifically. There was also some support for one additional independent moderate-risk allele in Swedish familial samples. The results were consistent with our previous findings in familial breast cancer and supported a breast cancer susceptibility locus at 6q14.1 around the PHIP gene.
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| 4. |
- Adamovic, Tatjana, 1974, et al.
(författare)
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Nonrandom pattern of chromosome aberrations in 17beta-estradiol-induced rat mammary tumors: indications of distinct pathways for tumor development.
- 2007
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Ingår i: Genes, chromosomes & cancer. - : Wiley. - 1045-2257 .- 1098-2264. ; 46:5, s. 459-69
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Tidskriftsartikel (refereegranskat)abstract
- Estrogens play an important role in breast cancer etiology and the ACI rat provides a novel animal model for defining the mechanisms through which estrogens contribute to mammary cancer development. In crossing experiments between the susceptible ACI strain and two resistant strains, COP (Copenhagen) and BN (Brown Norway), several quantitative trait loci (QTL) that affect development of 17beta-estradiol (E2)-induced mammary tumors have been defined. Using comparative genomic hybridization (CGH), we have analyzed cytogenetic aberrations in E2-induced mammary cancers and have found clear patterns of nonrandom chromosomal involvement. Approximately two thirds of the tumors exhibited copy number changes. Losses of rat chromosome 5 (RNO5) and RNO20 were particularly common, and it was found that these two aberrations often occurred together. A third recurrent aberration involving proximal gain and distal loss in RNO6 probably defined a distinct subgroup of tumors, since it never occurred in combination with RNO5 loss. Interestingly, QTL with powerful effects on mammary cancer development have been mapped to RNO5 and RNO6. These findings suggest that there were at least two genetic pathways to tumor formation in this rat model of E2-induced mammary cancer. By performing CGH on mammary tumors from ACI rats, F1 rats from crosses between the ACI and COP or BN strains and ACI.BN-Emca8 congenic rats, which carry the BN allele of the Emca8 QTL on RNO5 on the ACI genetic background, we were able to determine that the constitution of the germ line influences the pattern of chromosomal aberrations.
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| 5. |
- Adamovic, T, et al.
(författare)
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The p.G146A and p.P125P polymorphisms in the steroidogenic factor-1 (SF-1) gene do not affect the risk for hypospadias in Caucasians
- 2012
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Ingår i: Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation. - : S. Karger AG. - 1661-5433. ; 6:6, s. 292-297
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Tidskriftsartikel (refereegranskat)abstract
- Hypospadias is a frequent congenital malformation in boys and is characterized by incomplete fusion of the urethral folds. The steroidogenic factor-1 <i>(SF-1, NR5A1)</i> gene plays a key role in hypothalamic-pituitary-steroidogenic organ development, and has previously been reported to be mutated in individuals with 46,XY disorder of sex development. Here, we investigated the role of <i>SF-1</i> in hypospadias, a milder form of 46,XY disorder of sex development. We performed direct sequencing analysis of the <i>SF-1</i> gene in 2 male Caucasian twins exhibiting very severe hypospadias, and in 95 Caucasian boys with mild and severe hypospadias. We further extended the analysis by investigating 332 mild and severe hypospadias cases and 422 male controls using TaqMan assays. Our sequencing revealed a novel heterozygous p.R313H (c.938G>A) missense mutation in each twin, and no mutations in the 95 Caucasian cases. Instead, a missense p.G146A (c.437G>C), and a silent known p.P125P (c.375C>T) polymorphism, respectively, was found in several of the latter cases. Further investigation of the 2 polymorphisms in the larger material of cases and controls showed no significant genotypic or allelic association. In conclusion, the <i>SF-1</i> gene may not play a significant role in the development of hypospadias in Caucasians.
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| 6. |
- Jonason, Peter K., et al.
(författare)
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Country-level correlates of the Dark Triad traits in 49 countries
- 2020
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Ingår i: Journal of personality. - : Wiley. - 0022-3506 .- 1467-6494. ; 88:6, s. 1252-1267
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The Dark Triad traits (i.e., narcissism, psychopathy, Machiavellianism) capture individual differences in aversive personality to complement work on other taxonomies, such as the Big Five traits. However, the literature on the Dark Triad traits relies mostly on samples from English-speaking (i.e., Westernized) countries. We broadened the scope of this literature by sampling from a wider array of countries.Method: We drew on data from 49 countries (N = 11,723; 65.8% female;Age(Mean) = 21.53) to examine how an extensive net of country-level variables in economic status (e.g., Human Development Index), social relations (e.g., gender equality), political orientations (e.g., democracy), and cultural values (e.g., embeddedness) relate to country-level rates of the Dark Triad traits, as well as variance in the magnitude of sex differences in them.Results: Narcissism was especially sensitive to country-level variables. Countries with more embedded and hierarchical cultural systems weremorenarcissistic. Also, sex differences in narcissism werelargerinmoredeveloped societies: Women were less likely to be narcissistic in developed (vs. less developed) countries.Conclusions: We discuss the results based on evolutionary and social role models of personality and sex differences. That higher country-level narcissism was more common in less developed countries, whereas sex differences in narcissism were larger in more developed countries, is more consistent with evolutionary than social role models.
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| 7. |
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| 8. |
- Omrani, MD, et al.
(författare)
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17-β-hydroxysteroid dehydrogenase type 3 deficiency in three adult Iranian siblings
- 2011
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Ingår i: Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation. - : S. Karger AG. - 1661-5433. ; 5:6, s. 273-276
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Tidskriftsartikel (refereegranskat)abstract
- 17-β-hydroxysteroid dehydrogenase type 3 (17-β-HSD 3) deficiency is an autosomal recessive form of 46,XY disorder of sex development (DSD). To date, a total of 27 <i>HSD17B3</i> gene mutations have been described in 46,XY patients exhibiting different phenotypes at birth and virilization at puberty, sometimes in association with gynecomastia. Herein, we investigate the 46,XY DSD in an Iranian family consisting of 7 siblings, 3 of which are affected and virilized at puberty. We clinically characterized these patients andperformed direct DNA sequencing of the steroid 5-α-reductase type 2<i> (SRD5A2)</i> and the <i>HSD17B3</i> gene, respectively. We identified a homozygous mutation in the <i>HSD17B3 </i>gene (R80W; c.238C>G) in all affected siblings. No mutation was detected in the <i>SRD5A2 </i>gene. The detected mutation in the <i>HSD17B3 </i>gene was previously described in a newborn child, who died from other congenital malformations, and in a 12-year-old girl. Hence, our report adds novel value to the phenotype classification of 17-β-HSD 3 deficiency.
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| 9. |
- Rogoza, Radoslaw, et al.
(författare)
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Structure of Dark Triad Dirty Dozen Across Eight World Regions
- 2021
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Ingår i: Assessment (Odessa, Fla.). - : SAGE Publications. - 1073-1911 .- 1552-3489. ; 28:4, s. 1125-1135
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Tidskriftsartikel (refereegranskat)abstract
- The Dark Triad (i.e., narcissism, psychopathy, Machiavellianism) has garnered intense attention over the past 15 years. We examined the structure of these traits' measure-the Dark Triad Dirty Dozen (DTDD)-in a sample of 11,488 participants from three W.E.I.R.D. (i.e., North America, Oceania, Western Europe) and five non-W.E.I.R.D. (i.e., Asia, Middle East, non-Western Europe, South America, sub-Saharan Africa) world regions. The results confirmed the measurement invariance of the DTDD across participants' sex in all world regions, with men scoring higher than women on all traits (except for psychopathy in Asia, where the difference was not significant). We found evidence for metric (and partial scalar) measurement invariance within and between W.E.I.R.D. and non-W.E.I.R.D. world regions. The results generally support the structure of the DTDD.
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