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Genetic Heterogeneity between Migraine with Aura and Migraine without Aura Is HLA-DR2-Linked
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HLA and complement factors alleles sharing in italian couples with recurrent spontaneous abortions
No full textChromosome 6p- encoded HLA DR2 determinant discriminates migraine without aura from migraine with aura
No full textSegregation analysis indicates that migraine without aura (MWoA) and migraine with aura (MWA) have multifactorial inheritance, but involved genetic and environmental factors are largely unknown. A controlled study was performed to assess the HLA-driven liability to migraine and to verify if the heterogeneity between MWoA and MWA is HLA-linked. Forty-five migraine patients (31 MWoA, 14 MWA) and 53 healthy blood donors as controls, coming from the same geographic area, were studied. Tissue typing was performed using the standard complement-dependent microlymphocytotoxicity technique for HLA Class I and by PCR-SSP (Sequences Specific Primers) typing for HLA Class II. Data emerging from the present study showed no altered distribution for HLA Class I A, B, C antigen frequency in migraine (MWoA, MWA) if compared to the control group. HLA Class II DR2 antigen showed a decreased frequency in MWA group if compared with both MWoA (p = 0.01) and control group (p = 0.039, RR = 0.21). These results seem to support the hypothesis of a protective role of DR2 antigen in MWA and provide additional basis for the proposed difference within MWoA and MWA
Tumor necrosis factor (TNF) –B gene polymorphysm contributes to the susceptibility to migraine without aura
No full textMigraine without aura (MWOA) and migraine with aura (MWA) are disorders in which multiple factors, including environmental and genetic factors, are involved. In a previous study we hypothesized a protective role of HLA-DR2 antigen, providing additional basis for the proposed genetic heterogeneity between MWOA and MWA. The cytokines TNFA and TNFB are polypeptide effectors of inflammatory reaction and endothelial function. To better define the involvement of HLA region genes in migraine, we performed an association study of the tumor necrosis factor (TNF) genes, located in the HLA class III region, with MWOA and MWA. TNFB alleles 1 and 2 were analyzed by PCR-RFLP in 30 MWOA patients, in 47 MWA patients and in 101 random controls. The frequency of TNFB*2 was significantly increased in MWOA patients as compared with controls (78.72% vs. 61.4%, p c = 0.004), while no significant differences were found between MWA patients and controls. The distribution of TNFB genotypic frequencies showed a significant decrease of TNFB 1,1 homozygotes in MWOA patients (p c = 0.0201). The observed increase of TNFB*2 in MWOA is dustributed in TNFB 2,2 and TNFB 1,2 genotypes, meaning that the susceptibility allele could act as “dominant”: people with TNFB 1,1 genotype are less predisposed to the disease. While more studies are needed in larger migraine samples to reinforce the statistical power of the reported data, the present study supports the hypothesis that TNFB is a susceptibility gene in MWOA
HLA-DQ and susceptibility to celiac disease: Evidence for gender differences and parent-of-origin effects
No full textBACKGROUND AND AIMS: Celiac disease (CD) is twice as frequent among female than male. Despite the large number of reports on the DQ2/DQ8 association, no systematic studies have investigated a possible different role of the HLA genes in the two genders. We performed case-control and family-based analyses of DR-DQ variants in a pediatric CD cohort with the aim of comparing female to male associations and to investigate the paternal/maternal inheritance of the disease-predisposing haplotypes. METHODS: A total of 281 female and 156 male pediatric celiac patients, 292 nuclear families, and 551 controls were genotyped for HLA-DRB1, DQA1, and DQB1 loci. Odds ratio, parental origin of the disease-associated haplotypes, and transmission ratio distortion were valuated in-between male and female cases. RESULTS: DQ2/DQ8 were more frequent in female than in male patients (94% F, 85% M; P = 1.6 x 10(-3)) with a 99.1% and 90.5% calculated negative predictive value of the HLA test, respectively. Surprisingly, the majority of the 39 DQ2/DQ8 negative cases were male. The analysis of the DQ2 haplotype origin showed that 61% of female patients and 42% of male patients carried a paternal combination (P = 0.02). The transmission disequilibrium test (TDT) proved the major distortion in the DR3-DQ2 transmission from fathers to daughters. CONCLUSIONS: CD is confirmed to be more prevalent in female than in male (F:M = 1.8) but, in DQ2/DQ8 negative patients, we found an unexpected male excess (F:M = 0.7). Moreover, only the inheritance of a paternal DQ2 haplotype led to a daughters predominance. These data show a role of HLA genes on the disease sex bias and suggest a possible different effect of parent-specific epigenetic modifications in the two genders.Celiac disease (CD) is twice as frequent among female than male. Despite the large number of reports on the DQ2/DQ8 association, no systematic studies have investigated a possible different role of the HLA genes in the two genders. We performed case-control and family-based analyses of DR-DQ variants in a pediatric CD cohort with the aim of comparing female to male associations and to investigate the paternal/maternal inheritance of the disease-predisposing haplotypes.
METHODS:
A total of 281 female and 156 male pediatric celiac patients, 292 nuclear families, and 551 controls were genotyped for HLA-DRB1, DQA1, and DQB1 loci. Odds ratio, parental origin of the disease-associated haplotypes, and transmission ratio distortion were evaluated in-between male and female cases.
RESULTS:
DQ2/DQ8 were more frequent in female than in male patients (94% F, 85% M; P = 1.6 x 10(-3)) with a 99.1% and 90.5% calculated negative predictive value of the HLA test, respectively. Surprisingly, the majori
Tumor necrosis factor gene polymorphism in migraine
No full textOBJECTIVE: To better define the involvement of human leukocyte antigen region (HLA) genes in migraine via an association study of the tumor necrosis factor (TNF) genes, located in the HLA class III region, with migraine with and without aura. BACKGROUND: Migraine without aura and migraine with aura are disorders involving multiple factors-environmental and genetic. In a previous study, we hypothesized a protective role for the HLA-DR2 antigen, providing additional basis for the proposed genetic heterogeneity between migraine without aura and migraine with aura. The cytokines produced by TNF genes are polypeptide effectors of inflammatory reaction and endothelial function. METHODS: Tumor necrosis factor (TNF)-308 (TNF-308A and TNF-308G alleles) and lymphotoxin alpha (TNFB*1 and TNFB*2 alleles) polymorphisms were analyzed by the NcoI-cleaved polymerase chain reaction-amplified fragments in 47 patients with migraine without aura, 32 patients with migraine with aura, and 101 migraine-free controls. RESULTS: The frequency of TNFB*2 allele was significantly increased in our patients with migraine without aura as compared with the control group (78.72% versus 61.4%, Pc =.004), but no significant differences were found between patients with migraine with aura and controls. Additionally, there was a significant decrease of TNFB*1 homozygotes in patients with migraine without aura compared with the control group (2.13% versus 16.8%, Pc =.0201). Carriage of the TNFB*2 allele confers a high risk for the development of migraine without aura. No significant association was found at TNF-308 polymorphism. CONCLUSION: These data support the hypothesis that lymphotoxin alpha could be a susceptibility gene in migraine without aura and confirm previous data indicating that migraine with and without aura are distinct entities with different genetic backgrounds
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