A trio family study showing association of the lymphotoxin-α N26 (804A) allele with coronary artery disease

  title={A trio family study showing association of the lymphotoxin-$\alpha$ N26 (804A) allele with coronary artery disease},
  author={The Procardis Consortium},
  journal={European Journal of Human Genetics},
Family-based studies to map susceptibility genes through linkage disequilibrium have been successful in early-onset diseases where parental-proband trios are readily collected, but are believed to be unworkable for late-onset diseases such as coronary artery disease (CAD). PROCARDIS is a European multicentre study that was designed to identify susceptibility genes for CAD. We have tested the transmission of a putatively functional allele, lymphotoxin-α N26 (804A), in more than 400 PROCARDIS… 

Association of the lymphotoxin-α gene Thr26Asn polymorphism with severity of coronary atherosclerosis

Evidence is provided of an association between LTA genotype and the extent of coronary atherosclerosis in a large cohort of well-documented coronary artery disease patients.

Haplotype-based association of four lymphotoxin-alpha gene polymorphisms with the risk of coronary artery disease in Han Chinese.

A protective effect of the haplotype G-C-T-C on the occurrence of CAD is shown, suggesting the involvement of LTA in CAD pathogenesis.

Lymphotoxin-α and galectin-2 SNPs are not associated with myocardial infarction in two different German populations

In two MI populations of European descent with markedly different ascertainment strategies, it was not able to identify a significant association of SNPs in the LTA genomic region or the LGALS2 gene with MI.

[Identification of a novel lymphotoxin-alpha (LTA) gene associated with ankylosing spondylitis in Ningxia population].

The results suggest that there is a relevance between LTA and the susceptibility of AS, and it is identified that the LTA polymorphism may be associated with AS in Ningxia population.

Lymphotoxin-α Gene and Risk of Myocardial Infarction in 6,928 Cases and 2,712 Controls in the ISIS Case-Control Study

A meta-analysis found no significant association with CHD risk using a recessive model and only a modest association using a dominant model (with narrow confidence intervals around these risk estimates).

A functional polymorphism in the lymphotoxin-α gene is associated with carotid artery wall thickness: The Diabetes Heart Study

  • Yongmei LiuD. Herrington L. Wagenknecht
  • Medicine, Biology
    European journal of cardiovascular prevention and rehabilitation : official journal of the European Society of Cardiology, Working Groups on Epidemiology & Prevention and Cardiac Rehabilitation and Exercise Physiology
  • 2006
The LTA 252A/G polymorphism is moderately associated with sub-clinical atherosclerosis and is associated with common carotid artery intima-media thickness in 1088 siblings from 435 Diabetes Heart Study families.

Role of the OX40 ligand/receptor pair in coronary artery disease

Atherosclerosis is the pathological basis for coronary artery disease (CAD), the leading cause of morbidity and mortality in developed countries. CAD and atherosclerosis have long been known to have

Genome-Wide Mapping of Susceptibility to Coronary Artery Disease Identifies a Novel Replicated Locus on Chromosome 17

To the authors' knowledge, this is the first genome-wide linkage analysis to map, and replicate, a CAD locus, and the region on Chromosome 17 provides a compelling target within which to identify novel genes underlying CAD.

Inflammation as a risk factor for myocardial infarction

Findings indicate the importance of inflammation, especially the LTA cascade, in the pathogenesis of MI, and combined strategy of genetic and molecular-cellular biological approaches may be useful for clarification of the pathogenic of common diseases in general.



Functional SNPs in the lymphotoxin-α gene that are associated with susceptibility to myocardial infarction

A typographical error in the third sentence of the abstract resulted in the P value for the association being incorrectly reported as P = 0.00000033, when the correct value is 0.0000033.

Polymorphic structure of the tumor necrosis factor (TNF) locus: an NcoI polymorphism in the first intron of the human TNF-beta gene correlates with a variant amino acid in position 26 and a reduced level of TNF- beta production

Four TNFB alleles can be defined at the DNA level, and putative binding sites conserved between mouse and man in the 5' flanking region as well as in intron 1 of the TNF-beta gene, found also in other cytokine promoter sequences are reported.

Association study designs for complex diseases

With the discovery of massive numbers of genetic markers and the development of better tools for genotyping, association studies will inevitably proliferate and now is the time to consider critically the design of such studies to avoid the mistakes of the past and to maximize their potential to identify new components of disease.

Tests and estimates of allelic association in complex inheritance.

  • N. MortonA. Collins
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1998
Efficiency of the TDT is increased in multiplex families and by inclusion of normal sibs, approaching a case-control design with normal but not hyper normal controls, and efficiency for hypernormal controls is always greater than for random controls.

Use of siblings as controls in case‐control association studies

  • D. Curtis
  • Psychology
    Annals of human genetics
  • 1997
It is shown that the use of unaffected siblings as controls is, like the TDT, robust against bias due to population stratification and other sources, and is expected only to produce positive results when a marker is both associated and linked with the disease locus.

A comparative study of sibship tests of linkage and/or association.

This paper proposes an extension of one of three recent family-based tests of association and linkage that utilize unaffected siblings as surrogates for untyped parents and describes and compares the four tests in the context of a complex disease for both biallelic and multialle Lic markers, as well as for sibships of different sizes.

Methods for detection of parent-of-origin effects in genetic studies of case-parents triads.

  • C. Weinberg
  • Biology
    American journal of human genetics
  • 1999
This report reviews existing methods for detection of parent-of-origin effects, showing that each can be invalid under certain scenarios, and proposes new methods based on application of likelihood-based inference after stratification on both the parental mating type and the inherited number of copies of the allele under study.

The effects of human population structure on large genetic association studies

The consequences of population structure on association outcomes increase markedly with sample size, and one method for correcting for population structure (Genomic Control) is examined, which may not correct for structure if too few loci are used and may overcorrect in other settings, leading to substantial loss of power.

The effect of TNF*B gene polymorphism on TNF-alpha and -beta secretion levels in patients with insulin-dependent diabetes mellitus and healthy controls.

It is shown that the level of TNF-beta secreted correlates with the TNF*B genotype in healthy individuals and in IDDM patients, and the extended haplotype Bw62-DR4-T NF*B2/2 rather than IDDM per se is almost certainly responsible for the depressed T NF-beta secretion found in the IDDM-TNF-B2 homozygous cohort.