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Association of Raynaud's phenomenon with a polymorphism in the NOS1 gene.

ABSTRACT: Background: Raynaud's phenomenon (RP) describes the phenomenon of recurrent vasospasm of digital arteries, associated with skin colour changes: pallor, cyanosis and erythema. Twin studies have indicated a genetic predisposition for RP; however, the precise aetiology of RP remains unknown. It is thought that genetic variation in temperature-responsive or vasospastic genes might underlie RP so performed a candidate gene study in a large, population based sample. We assessed the association between RP and single nucleotide polymorphisms (SNPs) in the TRPA1, TRPM8, CALCA, CALCB and NOS1 genes.

Methods: Analysis included a total of 4276 individuals from the TwinsUK database. RP status had been determined using validated, self-administered questionnaires and was diagnosed in 640 individuals (17.6%). 66 tag SNPs across the candidate genes were tested for association with RP status using a linear regression model, accounting for covariates. Adjustment was made for multiple testing. RegulomeDB and GTEx databases were used to assess possible functional effects of the polymorphisms.

Results: Nominally significant associations between RP and four SNPs in NOS1 and one in CALCB were identified. After permutation testing, rs527590 SNP in NOS1 passed the significance threshold. RegulomeDB scores indicated an unlikely functional effect of this variant, while the survey of the GTEx database found the SNP and several variants in linkage disequilibrium to be cis-eQTLs in skin.

Conclusion: Results indicate that RP is associated with variation in gene NOS1. This finding may be related to the observation that the significant SNP in NOS1 is known to exhibit functional influence on the gene expression.

SUBMITTER: Munir S

PROVIDER: S-EPMC5919461 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Association of Raynaud's phenomenon with a polymorphism in the NOS1 gene.

Munir Sabrina S Freidin Maxim B MB Brain Susan S Williams Frances M K FMK

PloS one 20180426 4

<h4>Background</h4>Raynaud's phenomenon (RP) describes the phenomenon of recurrent vasospasm of digital arteries, associated with skin colour changes: pallor, cyanosis and erythema. Twin studies have indicated a genetic predisposition for RP; however, the precise aetiology of RP remains unknown. It is thought that genetic variation in temperature-responsive or vasospastic genes might underlie RP so performed a candidate gene study in a large, population based sample. We assessed the association ...[more]

PMID: 29698501

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Project description:BackgroundMany different drugs have been suggested for the symptomatic treatment of primary Raynaud's phenomenon. Apart from calcium channel blockers, which are considered the drugs of choice, the evidence of the effects of alternative pharmacological treatments is limited. This is an update of a review first published in 2008.ObjectivesTo assess the effects of various drugs with vasodilator actions on primary Raynaud's phenomenon.Search methodsFor this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched 14 May 2012), CENTRAL (Issue 4, 2012) and clinical trials databases. We contacted one pharmaceutical company and one trial author for additional information. In addition, the reference lists of relevant studies were searched for additional citations. There were no language restrictions.Selection criteriaRandomised controlled trials evaluating the effects of oral formulations of any drug with vasodilator effects on subjective symptoms in primary Raynaud's phenomenon. Treatment with, or comparison with, calcium channel blockers was not assessed in this review.Data collection and analysisTwo members of the review team independently assessed the trials for inclusion and their quality and extracted the data. Data extraction included adverse events. We contacted trial authors for missing data.Main resultsEight studies involving 290 participants were included. Two trials examined the effects of captopril, the rest were single trials on single drugs. All comparisons were with placebo. The methodological quality of most trials was poor.Enalapril was associated with a small increase in the frequency of attacks per week (difference in means 0.8; 95% CI 0.43 to 1.17). The difference between the intervention groups on a subjective improvement score was non-significant. There was a significant effect of buflomedil on the frequency of attacks per week (weighted mean difference (WMD) -8.8; 95% CI -17.55 to -0.09), but there was no evidence of effect on the severity score. The proportion with fewer attacks was significantly higher on moxisylyte than on placebo (relative risk (RR) 4.33; 95% CI 1.36 to 13.81). For captopril, beraprost, dazoxiben and ketanserin there was no evidence of an effect on the frequency, severity or duration of attacks. Beraprost and moxisylyte gave significantly more adverse effects than placebo.Authors' conclusionsPoor methodological quality, small sample sizes and the limited data available resulted in low precision of the statistical results and limited value of the overall results .The overall results show that there is no evidence for an effect of vasodilator drugs on primary Raynaud's phenomenon.

Project description:ObjectiveThe aim at the current study was to investigate the clinical characteristics and risk factors of Raynaud's phenomenon (RP) in patients with primary Sjögren's syndrome (pSS).MethodsRetrospective analysis of the medical records of 333 new-onset pSS patients was performed. Demographic, clinical, and serological data were compared between individuals with and without RP. Logistic regression analysis was used to identify risk factors.ResultsRP was present in 11.41% of the pSS patients. pSS-RP patients were younger (49.74±14.56 years vs. 54.46±13.20 years, p=0.04) and exhibited higher disease activity (11 [5.75-15] vs. 7 [4-12], p=0.03) than those without. The prevalence of lung involvement was significantly higher in pSS patients with RP (60.53% vs. 17.29%; p<0.001). A significantly higher proportion of patients with pSS-RP tested positive about antinuclear (ANA), anti-RNP, and anti-centromere antibodies (ACA) compared to those without (p=0.003, <0.001, and 0.01, respectively). Multivariate analysis identified lung involvement (odds ratio [OR]=8.81, 95% confidence interval [CI] 2.02-38.47; p=0.04), anti-RNP positive status (OR=79.41, 95% CI 12.57-501.78; p<0.0001), as well as ACA (OR=13.17, 95% CI 2.60-66.72; p=0.002) as prognostic factors for pSS-RP.ConclusionThe presence of RP defined a subset of pSS with a unique phenotype, manifesting as increased lung involvement and a higher frequency of anti-RNP antibodies and ACA, as well as greater disease activity. These results suggest that RP has clinical and prognostic value of pSS patients. Further prospective studies with a larger number of subjects are warranted to confirm our findings and assess the prognostic and treatment implications of RP in pSS patients. Key Points • Raynaud's phenomenon (RP) was present in 38 (11.41%) of 333 patients with primary Sjögren's syndrome (pSS), with patients with RP exhibiting a younger age and higher disease activity. • The presence of RP indicates a subset of pSS with a unique phenotype, with manifestations including increased lung involvement and a higher frequency of anti-RNP antibodies and anti-centromere antibodies. • Patients with pSS and RP need close follow-up and long-term observation (including assessment of microangiopathy), with specific attention paid to the possible development of clinical features of systemic sclerosis.

Dataset Information

Association of Raynaud's phenomenon with a polymorphism in the NOS1 gene.

Publications

Association of Raynaud's phenomenon with a polymorphism in the NOS1 gene.

Similar Datasets

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