RESUMEN
BACKGROUND: Genome wide association studies (GWAS) have already found different migraine single nucleotide polymorphisms (SNPs). To further check if these variants differ by ethnicity, three single nucleotide polymorphisms (SNPs) (rs4379368, rs10504861and rs11172113) were genotyped here to find association with migraine susceptibility from North Indian population. METHODS AND RESULTS: A case control study in 200 subjects was done by polymerase chain reaction and restriction-fragment-length polymorphism (PCR-RFLP) analysis. Univariate analysis was performed to check the association of different genotypic and allelic frequencies of these variants with migraine and its subtypes. We could not find any statistically relevant differences among frequencies at various levels of these selected SNPs between patients and healthy controls in this study (pâ¯>â¯0.05). However on subgroup analysis for rs4379368 SNP, the CT genotype was higher in migraine with aura (MA) (69.6%) than migraine without aura (MO) (51.9%) or control (42%) (pâ¯<â¯0.05). But this relation was not significant at allelic level. For other two SNPs, statistically significant differences were not observed in any of the two migraine subgroups. CONCLUSIONS: This study was able to associate the role of rs4379368 SNP with migraine susceptibility and suggested that genotype CT in rs4379368 SNP could be a possible genetic marker for MA. More studies with larger sample size are needed to strengthen our results.
Asunto(s)
Sitios Genéticos , Marcadores Genéticos , Predisposición Genética a la Enfermedad , Migraña con Aura/genética , Polimorfismo de Nucleótido Simple , Adulto , Alelos , Coenzima A Transferasas/genética , Femenino , Frecuencia de los Genes , Genotipo , Humanos , India , Proteína 1 Relacionada con Receptor de Lipoproteína de Baja Densidad/genética , Masculino , Proteínas de la Membrana/genética , Proteínas de Unión al ARN/genéticaRESUMEN
Recently a GWAS study had identified 38 genomic variants commonly found in humans that influence migraine risk. For further replicate these findings, we selected two SNPs; rs2651899 on chromosome 1p36.32 in PRDM16 gene and rs10166942 on chromosome 2q37.1 close to TRPM8 gene for their associations with migraine in the North Indian population as much work has not been done on these variants before from this population. In this case-control association study, 300 unrelated subjects, including 150 migraineurs (43 migraine with aura and 107 migraine without aura) and 150 healthy controls were selected to collect genomic DNA. Polymerase chain reaction and restriction-fragment-length polymorphism methods were performed for genotyping of these variants. Univariate and multivariate analyses were done to find the association of different genotypes and alleles of these SNPs with migraine and its subgroups. We found a statistically significant difference in migraineurs with control for PRDM16 rs2651899 polymorphism at genotypic (p < 0.05), allelic (p = 0.022; OR 1.462; 95% CI 1.058-2.022) and for dominant model (p = 0.011; OR 1.957; 95% CI 1.169-3.276). A similar trend was observed both on subgroup and gender analysis in migraine without aura (MO) and females respectively for rs2651899 variant. For the other SNP (rs10166942), statistically non-significant differences were reported in the allelic/genotypic frequencies between migraineurs and controls as p > 0.05. However, on subgroup analysis we found statistically significant differences at genotypic (p < 0.05) and dominant models in migraine with aura (MA) and in males with that of entire controls. But no significant association was found at allelic level in both subgroup and gender analysis for rs10166942. This research study showed that rs2651899 is a potential genetic marker for migraine susceptibility in MO and female subgroup at both genotypic and allelic level in the North Indian population and found that rs10166942 variant may be a potential marker for MA and male subgroup. Further work with large sample size is required for these SNPs to understand their functional mechanisms and to strengthen our results.
Asunto(s)
Proteínas de Unión al ADN/genética , Migraña sin Aura/genética , Canales Catiónicos TRPM/genética , Factores de Transcripción/genética , Adulto , Alelos , Pueblo Asiatico/genética , Estudios de Casos y Controles , Proteínas de Unión al ADN/fisiología , Femenino , Frecuencia de los Genes/genética , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Genotipo , Humanos , India , Masculino , Persona de Mediana Edad , Trastornos Migrañosos/genética , Migraña sin Aura/fisiopatología , Polimorfismo de Nucleótido Simple/genética , Factores de Riesgo , Canales Catiónicos TRPM/metabolismo , Factores de Transcripción/fisiologíaRESUMEN
Polymorphisms in MTHFR gene are mostly associated with increased levels of homocysteine in the absence of dietary folate and are a risk factor for complex neurovascular diseases like migraine. The aim of present case-control study was to determine the association between MTHFR gene polymorphisms (C667T; rs 1801133, A1298C; rs 1801131) with migraine susceptibility. In total, 100 patients with migraine (23with MA and 77 with MO) and age-sex matched 100 healthy controls were included in this study from OPD of ESIC Medical College & Hospital, Faridabad. Genotyping was done by PCR-RFLP method. Genotypic and allelic frequencies were compared by SPSS 24 version. Genotypic results indicated a non-significant increase in frequencies of CT and TT in C667T SNP in migraine patients with control (52 and 10% vs. 42 and 7%: p > 0.05), but CC genotype in A1298C was found to be a risk factor in migraine patients than controls (30 vs. 17% respectively: p < 0.05). On comparing migraine subclasses, migraine with aura (MA) and without aura (MO) with control groups, the present study suggests that in MTHFR polymorphisms, the prevalence of 677CT genotype and T allele in C667T SNP influences susceptibility to MA (p < 0.05) but not to MO. Meanwhile, CC genotype in A1298C SNP could be a risk factor for migraine patients without aura (p < 0.05).