Single nucleotide polymorphisms in the dystroglycan gene do not correlate with disease severity in hereditary inclusion body myopathy

Multiple sclerosis is a heterogeneous neurological disease with varying degrees of severity. The common hypothesis is that susceptibility to multiple sclerosis and its phenotype are caused by a combination of environmental and genetic factors. The genetic part exerts its effect through several genes, each having modest effects. We evaluated whether disease severity could be predicted by a model based on clinical data and data from a DNA chip. The DNA chip was designed containing several single nucleotide polymorphisms in 44 genes, previously described to be associated with multiple sclerosis. A total of 605 patients with multiple sclerosis were included in this analysis, using gender, onset type and age at onset as clinical covariates. We correlated 80 single nucleotide polymorphisms to the degree of disease severity using the following three outcome measures: linear Multiple Sclerosis Severity Score, dichotomous Multiple Sclerosis Severity Score (using a cut-off point of 2.5) and time to reach Expanded Disability Status Scale score 6. Sixty-nine single nucleotide polymorphisms were included in the analysis. No individual single nucleotide polymorphism showed a significant association; however, a combination of single nucleotide polymorphisms significantly improved the prediction of disease severity in addition to the clinical variables. In all three models the Interleukin 2 gene was included, confirming a previously reported modest effect on disease severity. The highest power was obtained using the dichotomized Multiple Sclerosis Severity Score as outcome. Several single nucleotide polymorphisms showed their added predictive value over the clinical data in the predictive models. These results support our hypothesis that disease severity is determined by clinical variables and genetic influences (through several genes with small effects) in concert.

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CLC-2 single nucleotide polymorphisms (SNPs) as potential modifiers of cystic fibrosis disease severity

BMC Medical Genetics ◽

10.1186/1471-2350-5-26 ◽

2004 ◽

Vol 5 (1) ◽

Cited By ~ 9

Author(s):

Carol J Blaisdell ◽

Timothy D Howard ◽

Augustus Stern ◽

Penelope Bamford ◽

Eugene R Bleecker ◽

...

Keyword(s):

Cystic Fibrosis ◽

Single Nucleotide Polymorphisms ◽

Disease Severity ◽

Nucleotide Polymorphisms ◽

Single Nucleotide

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Single nucleotide polymorphisms of the HIF1A gene are associated with susceptibility to pulmonary arterial hypertension in systemic sclerosis and contribute to SSc‐PAH disease severity

International Journal of Rheumatic Diseases ◽

10.1111/1756-185x.13822 ◽

2020 ◽

Vol 23 (5) ◽

pp. 674-680

Author(s):

Kae Takagi ◽

Manabu Kawamoto ◽

Tomoaki Higuchi ◽

Akiko Tochimoto ◽

Masayoshi Harigai ◽

...

Keyword(s):

Systemic Sclerosis ◽

Pulmonary Arterial Hypertension ◽

Single Nucleotide Polymorphisms ◽

Arterial Hypertension ◽

Disease Severity ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Pulmonary Arterial ◽

Hif1a Gene

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HIV-1 Promoter Single Nucleotide Polymorphisms Are Associated with Clinical Disease Severity

PLoS ONE ◽

10.1371/journal.pone.0150835 ◽

2016 ◽

Vol 11 (4) ◽

pp. e0150835 ◽

Cited By ~ 10

Author(s):

Michael R. Nonnemacher ◽

Vanessa Pirrone ◽

Rui Feng ◽

Brian Moldover ◽

Shendra Passic ◽

...

Keyword(s):

Single Nucleotide Polymorphisms ◽

Disease Severity ◽

Clinical Disease ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Hiv 1

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Interleukin-10 promoter single-nucleotide polymorphisms as markers for disease susceptibility and disease severity in leprosy

Genes and Immunity ◽

10.1038/sj.gene.6364122 ◽

2004 ◽

Vol 5 (7) ◽

pp. 592-595 ◽

Cited By ~ 52

Author(s):

MO Moraes ◽

AG Pacheco ◽

JJM Schonkeren ◽

PR Vanderborght ◽

JAC Nery ◽

...

Keyword(s):

Single Nucleotide Polymorphisms ◽

Disease Severity ◽

Disease Susceptibility ◽

Interleukin 10 ◽

Nucleotide Polymorphisms ◽

Single Nucleotide

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Multiplex Screening of 22 Single-Nucleotide Polymorphisms in 7 Toll-like Receptors: An Association Study in Rheumatoid Arthritis

The Journal of Rheumatology ◽

10.3899/jrheum.090775 ◽

2010 ◽

Vol 37 (5) ◽

pp. 905-910 ◽

Cited By ~ 14

Author(s):

CHRISTIAN ENEVOLD ◽

TIMOTHY R.D. RADSTAKE ◽

MARIEKE J.H. COENEN ◽

JAAP FRANSEN ◽

ERIK J.M. TOONEN ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Single Nucleotide Polymorphisms ◽

Disease Activity ◽

Disease Severity ◽

Clinical Characteristics ◽

Nucleotide Polymorphisms ◽

Toll Like Receptors ◽

Inception Cohort ◽

Single Nucleotide ◽

Functional Variants

Objective.Toll-like receptors (TLR) have been implicated in the pathogenesis of arthritis. We investigated the role of functional variants of TLR in the disease phenotype and severity of rheumatoid arthritis (RA).Methods.All patients from a longterm observational inception cohort (n = 319) were genotyped for 22 single-nucleotide polymorphisms (SNP) in TLR2, 3, 4, 5, 7, 8, and 9 using multiplex assays. Clinical characteristics including sex, age at disease onset, rheumatoid factor (RF), and shared epitope positivity and disease activity score and radiological progression were taken into account. Genotypes were analyzed for association with Disease Activity Scores (DAS28) and joint damage (Rau scores) at 3 and 6 years.Results.After Bonferroni correction, there was a moderate association between RF positivity and TLR8-rs5741883. No other TLR variant was significantly associated with any RA clinical characteristics.Conclusion.Using a large inception cohort and strict statistical evaluation, we could not identify an association between functional TLR variants and RA phenotype and disease severity. This suggests the functional TLR variants do not play a major role in RA phenotype and disease severity.

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