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Association Between MTHFR Genetic Variants and Multiple Sclerosis in a Southern Iranian Population.

Naghibalhossaini F, Ehyakonandeh H, Nikseresht A, Kamali E - Int J Mol Cell Med (2015)

Bottom Line: Genetic predisposition has long been suspected in the etiology of this disease.The association between MTHFR polymorphisms and MS has been ivestigated in different ethnic groups.Our results suggest a possible gene dose- dependent association between MTHFR mutrant alleles and the risk of MS development.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Shiraz University of Medical Sciences, School of Medicine, Shiraz, Iran. ; Autoimmune Research Center, Shiraz University of Medical Sciences, School of Medicine, Shiraz, Iran.

ABSTRACT
Multiple sclerosis (MS) is a demyelinating neuro- inflammatory autoimmune disease of the central nervous system. Genetic predisposition has long been suspected in the etiology of this disease. The association between MTHFR polymorphisms and MS has been ivestigated in different ethnic groups. We investigated the association between MTHFR C677T and A1298C missense variants and MS in 180 patients and 231 age- and gender-matched healthy controls in a Southern Iranian population. The mutagenically separated PCR (MS-PCR) and PCR-RFLP methods were used to genotype MTHFR at position 677 and 1298, respectively. Compared with controls, we observed a strong association between two MTHFR variants and the risk of developing MS. Subjects carrying 677T allele (CT and TT genotypes) had increased susceptibility to MS as compared to those carrying CC genotype (odds ratio (OR) for CT= 2.9, 95% confidence interval (95% CI)= 1.88-4.49; OR for TT= 6.23, 95% CI= 3.08-12.59). The variant 1298AC genotype also increased the risk for MS among our study population (OR= 2.14, 95% CI= 1.37-3.34). Combined genotype analysis for two MTHFR SNPs revealed that compared to the wild type genotypes (677CC/1298AA), 3 genotypes including TT/AC, CT/AC, and TT/AA were significantly at increased risk for MS development (OR= 13.9, 5.3, and 4.9, respectively). Our results suggest a possible gene dose- dependent association between MTHFR mutrant alleles and the risk of MS development.

No MeSH data available.


Related in: MedlinePlus

Representative examples of genotyping of MTHFR positions 677 and 1298. A. MS-PCR assay for the genotyping of MTHFR C677T polymorphism. The 677C alleles (168 base pair product) were separated from the 677T alleles (148-base pair product) by electrophoresis on a 2.5 % agarose gel. B. PCR-RFLP assay for genotyping of MTHFR A1298C polymorphisms. Digestion of the 163 bp PCR product of the 1298A allele yields five fragments of 56, 31, 30, 28, and 18 base pairs, whereas the 1298C allele results in four PCR bands of 84, 31, 30, and 18 base pairs. The digested PCR products were separated by electrophoresis on a 2.5% agarose gel. The three possible genotypes are discernible by detection of the 84and 56 bp fragments
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Figure 1: Representative examples of genotyping of MTHFR positions 677 and 1298. A. MS-PCR assay for the genotyping of MTHFR C677T polymorphism. The 677C alleles (168 base pair product) were separated from the 677T alleles (148-base pair product) by electrophoresis on a 2.5 % agarose gel. B. PCR-RFLP assay for genotyping of MTHFR A1298C polymorphisms. Digestion of the 163 bp PCR product of the 1298A allele yields five fragments of 56, 31, 30, 28, and 18 base pairs, whereas the 1298C allele results in four PCR bands of 84, 31, 30, and 18 base pairs. The digested PCR products were separated by electrophoresis on a 2.5% agarose gel. The three possible genotypes are discernible by detection of the 84and 56 bp fragments

Mentions: MTHFR C677T and A1298C genotyping was performed by MS-PCR and PCR-RFLP methods, respectively. Illustrative examples of genotype analysis of the two MTHFR variant genotypes are shown in Fig. 1. The results of genotype frequencies and odds ratios for MTHFR genotypes and MS are presented in Table 1. There was no significant HardyWeinberg disequilibrium concer-ning the MTHFR 677 and 1298 genotypes in controls. The distribution of MTHFR 677 genotypes among patients also agreed with that expected from the Hardy-Weinberg equilibrium (χ2= 0.5, P= 0.47). However, significant departures from Hardy-Weinberg equilibrium were observed for MTHFR 1298 genotypes among cases (P= 0.00).


Association Between MTHFR Genetic Variants and Multiple Sclerosis in a Southern Iranian Population.

Naghibalhossaini F, Ehyakonandeh H, Nikseresht A, Kamali E - Int J Mol Cell Med (2015)

Representative examples of genotyping of MTHFR positions 677 and 1298. A. MS-PCR assay for the genotyping of MTHFR C677T polymorphism. The 677C alleles (168 base pair product) were separated from the 677T alleles (148-base pair product) by electrophoresis on a 2.5 % agarose gel. B. PCR-RFLP assay for genotyping of MTHFR A1298C polymorphisms. Digestion of the 163 bp PCR product of the 1298A allele yields five fragments of 56, 31, 30, 28, and 18 base pairs, whereas the 1298C allele results in four PCR bands of 84, 31, 30, and 18 base pairs. The digested PCR products were separated by electrophoresis on a 2.5% agarose gel. The three possible genotypes are discernible by detection of the 84and 56 bp fragments
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4499570&req=5

Figure 1: Representative examples of genotyping of MTHFR positions 677 and 1298. A. MS-PCR assay for the genotyping of MTHFR C677T polymorphism. The 677C alleles (168 base pair product) were separated from the 677T alleles (148-base pair product) by electrophoresis on a 2.5 % agarose gel. B. PCR-RFLP assay for genotyping of MTHFR A1298C polymorphisms. Digestion of the 163 bp PCR product of the 1298A allele yields five fragments of 56, 31, 30, 28, and 18 base pairs, whereas the 1298C allele results in four PCR bands of 84, 31, 30, and 18 base pairs. The digested PCR products were separated by electrophoresis on a 2.5% agarose gel. The three possible genotypes are discernible by detection of the 84and 56 bp fragments
Mentions: MTHFR C677T and A1298C genotyping was performed by MS-PCR and PCR-RFLP methods, respectively. Illustrative examples of genotype analysis of the two MTHFR variant genotypes are shown in Fig. 1. The results of genotype frequencies and odds ratios for MTHFR genotypes and MS are presented in Table 1. There was no significant HardyWeinberg disequilibrium concer-ning the MTHFR 677 and 1298 genotypes in controls. The distribution of MTHFR 677 genotypes among patients also agreed with that expected from the Hardy-Weinberg equilibrium (χ2= 0.5, P= 0.47). However, significant departures from Hardy-Weinberg equilibrium were observed for MTHFR 1298 genotypes among cases (P= 0.00).

Bottom Line: Genetic predisposition has long been suspected in the etiology of this disease.The association between MTHFR polymorphisms and MS has been ivestigated in different ethnic groups.Our results suggest a possible gene dose- dependent association between MTHFR mutrant alleles and the risk of MS development.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Shiraz University of Medical Sciences, School of Medicine, Shiraz, Iran. ; Autoimmune Research Center, Shiraz University of Medical Sciences, School of Medicine, Shiraz, Iran.

ABSTRACT
Multiple sclerosis (MS) is a demyelinating neuro- inflammatory autoimmune disease of the central nervous system. Genetic predisposition has long been suspected in the etiology of this disease. The association between MTHFR polymorphisms and MS has been ivestigated in different ethnic groups. We investigated the association between MTHFR C677T and A1298C missense variants and MS in 180 patients and 231 age- and gender-matched healthy controls in a Southern Iranian population. The mutagenically separated PCR (MS-PCR) and PCR-RFLP methods were used to genotype MTHFR at position 677 and 1298, respectively. Compared with controls, we observed a strong association between two MTHFR variants and the risk of developing MS. Subjects carrying 677T allele (CT and TT genotypes) had increased susceptibility to MS as compared to those carrying CC genotype (odds ratio (OR) for CT= 2.9, 95% confidence interval (95% CI)= 1.88-4.49; OR for TT= 6.23, 95% CI= 3.08-12.59). The variant 1298AC genotype also increased the risk for MS among our study population (OR= 2.14, 95% CI= 1.37-3.34). Combined genotype analysis for two MTHFR SNPs revealed that compared to the wild type genotypes (677CC/1298AA), 3 genotypes including TT/AC, CT/AC, and TT/AA were significantly at increased risk for MS development (OR= 13.9, 5.3, and 4.9, respectively). Our results suggest a possible gene dose- dependent association between MTHFR mutrant alleles and the risk of MS development.

No MeSH data available.


Related in: MedlinePlus