Genetic Factors in Cardiovascular Diseases*

McKusick, Victor A.

doi:10.1111/j.1532-5415.1961.tb01627.x

Cited by 6 publications

(2 citation statements)

References 19 publications

(17 reference statements)

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“…These features were reported to occur in 43%, 64%, 39%, 70% and 61% of cases, respectively, in a large-scale clinical study of HOS cases. 5 Several families have been reported to show anticipation in successive generations with no obvious genetic mechanism and explanation, 5,[15][16][17] and this phenomenon could be observed in the cardiac features in our family. Generations I-III had predominantly conduction abnormalities, and there is the occurrence of increasing severity of congenital heart defects in generations III-V (III:1-septal defect; IV:3-AVSD/PS; V:1-HLHS), but this could, however, be ascertainment bias.…”

Section: Discussionsupporting

confidence: 52%

TBX5 intragenic duplication: a family with an atypical Holt–Oram syndrome phenotype

Patel

Silcock²,

McMullan³

et al. 2012

Eur J Hum Genet

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Holt-Oram syndrome (HOS) is a rare autosomal dominant heart-hand syndrome due to mutations in the TBX5 transcription factor. Affected individuals can have structural cardiac defects and/or conduction abnormalities, and exclusively upper limb defects (typically bilateral, asymmetrical radial ray defects). TBX5 mutations reported include nonsense, missense, splicing mutations and exon deletions. Most result in a null allele and haploinsufficiency, but some impair nuclear localisation of TBX5 protein or disrupt its interaction with co-factors and downstream targets. We present a five generation family of nine affected individuals with an atypical HOS phenotype, consisting of ulnar ray defects (ulnar hypoplasia, short fifth fingers with clinodactyly) and very mild radial ray defects (short thumbs, bowing of the radius and dislocation of the radial head). The cardiac defects seen are those more rarely reported in HOS (atrioventricular septal defect, hypoplastic left heart syndrome, mitral valve disease and pulmonary stenosis). Conduction abnormalities include atrial fibrillation, atrial flutter and sick sinus syndrome. TBX5 mutation screening (exons 3-10) identified no mutations. Array comparative genomic hybridisation (CGH) revealed a 48 kb duplication at 12q24.21, encompassing exons 2-9 of the TBX5 gene, with breakpoints within introns 1-2 and 9-10. The duplication segregates with the phenotype in the family, and is likely to be pathogenic. This is the first known report of an intragenic duplication of TBX5 and its clinical effects; an atypical HOS phenotype. Further functional studies are needed to establish the effects of the duplication and pathogenic mechanism. All typical/atypical HOS cases should be screened for TBX5 exon duplications.

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Section: Discussionsupporting

confidence: 52%

TBX5 intragenic duplication: a family with an atypical Holt–Oram syndrome phenotype

Patel

Silcock²,

McMullan³

et al. 2012

Eur J Hum Genet

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“…Therefore, the pathogenesis of CVDs have been deemed as both genetic and inflammatory pathways, which modulated by various inflammatory cytokines. Genetic factors are regarded as strong determinants of CVDs (Brigitta, 2007; Mckusick, 1959). According to the chromosomal location and functional relevance, IL‐10 is a multifunctional cytokine that has been considered as a candidate gene for kinds of CVD (Couper, Blount, & Riley, 2008; Dopheide et al, 2015; Eskdale, Wordsworth, Bowman, Field, & Gallagher, 2010; Heeschen et al, 2003a).…”

Section: Discussionmentioning

confidence: 99%

Association of IL‐10‐1082A/G polymorphism with cardiovascular disease risk: Evidence from a case–control study to an updated meta‐analysis

Zhong

Huang

et al. 2019

Molec Gen & Gen Med

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BackgroundPrevious studies have generated controversial results about the association of interleukin 10 (IL‐10) gene polymorphisms (−1082G/A) in the progression of cardiovascular disease (CVD). Therefore, this study processed a systemic meta‐analysis to verify this association.MethodsThe publication studies on the IL‐10 (−1082G/A) polymorphism and CVDs risk were obtained by searching PubMed and Embase databases. We analyzed the genotype data for meta‐analysis. The results were evaluated by odds ratios (ORs) and 95% confidence intervals (CIs). Meanwhile, our meta‐analysis was also performed sensitivity analyses, heterogeneity test, and identification of publication bias.ResultsThe present meta‐analysis suggested that the risk with allele G is lower than with allele A for CVD. The G allele of IL‐10 (−1082) could increase the risk of CVDs in the 31 case–control studies for all genetic models. (OR = 1.10, 95% CI: 1.04–1.15 for the allele model A vs. G; OR = 0.87, 95% CI: 0.72–1.04 for the dominant model GG+AG vs. AA; OR = 1.03, 95% CI: 1.02–1.05 for the recessive model GG vs. AG + AA; OR = 1.06, 95% CI = 1.03–1.10 for the homozygote comparison model GG vs. AA; and OR = 0.88, 95% CI = 0.73–1.06 for the heterozygote comparison model AG vs. AA).ConclusionsIn genetic models, the association between the IL‐10 (−1082G/A) polymorphism and CVDs risk was significant. This meta‐analysis proposes that the IL‐10 (−1082G/A) polymorphism may serve as a risk factor for CVDs.

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