HLA-DRB1*15:01 and multiple sclerosis: a female association?

Irizar, Haritz; Muñoz-Culla, Maider; Zuriarrain, O.; Goyenechea, Estíbaliz; Castillo-Triviño, Tamara; Prada, Álvaro; Sáenz-Cuesta, Matías; Juan, Dolores De; Munáin, Adolfo López de; Olascoaga, Javier; Otaegui, David

doi:10.1177/1352458511426813

Cited by 61 publications

(51 citation statements)

References 38 publications

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“…However, the significant association between DRB1*15:01 and MS was female-specific (Table 4), consistent with previous reports based on different populations 20,21 . Indeed, women are twice as likely as men to develop MS, and this disparity has been increasing for at least 50 years in certain populations 2 .…”

Section: Discussionsupporting

confidence: 82%

The CIITA genetic polymorphism rs4774C in combination with the HLA-DRB115:01 allele as a putative susceptibility factor to multiple sclerosis in Brazilian females

Paradela

Alves-Leon

Figueiredo

et al. 2015

Arq. Neuro-Psiquiatr.

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The objective of this study was to investigate the association between the HLA alleles at the DQA1, DQB1 and DRB1 loci, the CIITA genetic polymorphisms -168A/G and +1614G/C, and susceptibility to multiple sclerosis (MS) in a sample from Rio de Janeiro State, Brazil. Furthermore, we wished to determine whether any of these associations might be more significant in women compared with men. DNA samples from 52 relapsing-remitting MS (RRMS) patients and 126 healthy controls matched for sex and age were analyzed. We identified a significant HLA-DRB1*15:01-MS association that was female-specific (Odds Ratio (OR) = 4.78; p = 0.001). Furthermore, we observed that the +1614G/C mutation in combination with the HLA-DRB1*15:01 allele increased susceptibility to MS in females (OR = 4.55; p = 0.01). Together, these findings highlight the polygenic nature of MS.

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Section: Discussionsupporting

confidence: 82%

The CIITA genetic polymorphism rs4774C in combination with the HLA-DRB115:01 allele as a putative susceptibility factor to multiple sclerosis in Brazilian females

Paradela

Alves-Leon

Figueiredo

et al. 2015

Arq. Neuro-Psiquiatr.

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show abstract

“…The presence of DRB1*15 has also been associated with more disability, more severe spinal cord pathology, positive oligoclonal bands, more potent humoral responses to Epstein-Barr virus, female susceptibility to the disease and earlier onset [11][12][13][14][15]. On the other hand, in some populations, DRB1*01, DRB1*07, DRB1*11 and DRB1*14 appeared to provide protection from the disease [16].…”

Section: Introductionmentioning

confidence: 99%

HLA-DRB1* Allele Frequencies in Pediatric, Adolescent and Adult-Onset Multiple Sclerosis Patients, in a Hellenic Sample. Evidence for New and Established Associations

Anagnostouli¹,

Manouseli²

2013

J Mult Scler

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Studies in many populations consistently have showed that the human leukocyte antigens (HLA) and especially the DRB1 * 15 allele has by far the strongest genetic association with multiple sclerosis (MS). The aim of this study was to investigate the role of HLA-DRB1 * alleles in MS risk/resistance and onset. A sample of 165 Hellenic MS patients (18 with pediatric-, 24 with adolescent-and 123 with adult-onset MS) and 107 healthy volunteers were examined with molecular techniques. Comparisons were made according to the Benjamini-Yekutieli method for p value correction. Both adult-onset MS patients and early-onset MS patients (age at onset below 20 years-old) had a significantly higher frequency of the DRB1 * 15 allele and a significantly lower frequency of the DRB1 * 11 allele compared to controls. For the early-onset vs. healthy group comparison, subgroup analyses revealed that both the pediatric-and the adolescent-onset MS groups contributed to the aforementioned DRB1 * 15 significant difference, while the DRB1*11 difference was ascribed solely to the adolescent-MS onset vs. healthy group comparison. Within MS patients comparisons revealed that early-onset MS patients had a tendency for higher DRB1 * 03 allele and a lower DRB1 * 16 allele frequency frequencies compared to adult-onset MS patients, although both non-significant. Notably, pediatric-onset MS patients showed complete absence of the DRB1 * 16 allele, along with a non-significant tendency for higher DRB1 * 15 allele frequency relative to the adult-onset group. Finally, the adolescent-onset MS group was presented with a lower DRB1 * 11 allele frequencies compared both to the pediatric-and the adult-onset MS group. Our findings confirm previous studies on the role of HLA-DRB1 * in MS. New findings that need to be confirmed by further studies are the pathogenetic role of DRB1 * 03 for early-onset MS and the putative protective role of the DRB1*16 allele in the pediatric-onset MS.

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“…31 Therefore, 13 case-control studies reporting genotypic frequencies in cases and in controls were included in meta-analyses. 3,18,19,21,[23][24][25][26][27][28][29]32,33 The studies were heterogeneous for population composition and for geographic characteristics. Each study character was subdivided into different subgroups.…”

Section: Characteristics Of Studiesmentioning

confidence: 99%

“…However, there are several other functional VDR single nucleotide polymorphisms in the complex promoter region of the VDR gene. The interaction of the VDR gene with HLA genes have been shown to be significant in MS. 18,27,29,32 Interestingly, environmental factors may interact with VDR polymorphisms to modify MS risk. The current study could not evaluate all interactions between study characteristics and VDR polymorphisms due to insufficient information from the primary publications.…”

mentioning

confidence: 99%

Association between vitamin D receptor polymorphisms and multiple sclerosis: systematic review and meta-analysis of case–control studies

et al. 2014

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Vitamin D receptor (VDR) polymorphisms have been studied as potential contributors to multiple sclerosis (MS). However, published studies differ with respect to study design and the significance of the effects detected. The aim of this study was to quantify the magnitude of the risk associated with the TaqI, BsmI, ApaI and FokI VDR polymorphisms in MS using a meta-analysis approach. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we conducted a systematic search and meta-analysis of the literature. Subgroup analyses were performed to detect potential sources of heterogeneity from the selected study characteristics. The stability of the summary risk was evaluated using sensitivity analyses. The meta-analysis included a total of 3300 cases and 3194 controls from 13 casecontrol studies. There were no significant associations found between TaqI and BsmI polymorphisms and MS risk. The association between the ApaI polymorphism and MS risk was significant in the homozygous and codominant models (P50.013 and P50.031, respectively), suggesting that the AA ApaI genotype might be a significant MS risk factor. Publication year and age significantly affected the association between TaqI polymorphisms and MS (P50.014 and P50.010, respectively), which indicates a protective effect of the major T allele. The AA ApaI and FF FokI genotypes are significant risk factors for MS. The association between the TaqI polymorphism and MS risk is significantly affected by study characteristics.

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HLA-DRB1*15:01 and multiple sclerosis: a female association?

Abstract: We confirm the 15:01-MS association and support that it is female specific. The relevance of ethnic origin on association studies has also been highlighted. HLA-DRB115:01 seems to be a haplotype consistently linked to high HLA II gene expression.

Cited by 61 publications

References 38 publications

The CIITA genetic polymorphism rs4774C in combination with the HLA-DRB115:01 allele as a putative susceptibility factor to multiple sclerosis in Brazilian females

The CIITA genetic polymorphism rs4774C in combination with the HLA-DRB115:01 allele as a putative susceptibility factor to multiple sclerosis in Brazilian females

HLA-DRB1* Allele Frequencies in Pediatric, Adolescent and Adult-Onset Multiple Sclerosis Patients, in a Hellenic Sample. Evidence for New and Established Associations

Association between vitamin D receptor polymorphisms and multiple sclerosis: systematic review and meta-analysis of case–control studies

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HLA-DRB1*15:01 and multiple sclerosis: a female association?

Abstract: We confirm the *15:01-MS association and support that it is female specific. The relevance of ethnic origin on association studies has also been highlighted. HLA-DRB1*15:01 seems to be a haplotype consistently linked to high HLA II gene expression.

Cited by 61 publications

References 38 publications

The CIITA genetic polymorphism rs4774*C in combination with the HLA-DRB1*15:01 allele as a putative susceptibility factor to multiple sclerosis in Brazilian females

The CIITA genetic polymorphism rs4774*C in combination with the HLA-DRB1*15:01 allele as a putative susceptibility factor to multiple sclerosis in Brazilian females

HLA-DRB1* Allele Frequencies in Pediatric, Adolescent and Adult-Onset Multiple Sclerosis Patients, in a Hellenic Sample. Evidence for New and Established Associations

Association between vitamin D receptor polymorphisms and multiple sclerosis: systematic review and meta-analysis of case–control studies

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Abstract: We confirm the 15:01-MS association and support that it is female specific. The relevance of ethnic origin on association studies has also been highlighted. HLA-DRB115:01 seems to be a haplotype consistently linked to high HLA II gene expression.

The CIITA genetic polymorphism rs4774C in combination with the HLA-DRB115:01 allele as a putative susceptibility factor to multiple sclerosis in Brazilian females

The CIITA genetic polymorphism rs4774C in combination with the HLA-DRB115:01 allele as a putative susceptibility factor to multiple sclerosis in Brazilian females