Lack of association of transthyretin variations with spinocerebellar ataxia in north Indian population
- Author:
Mohammed Faruq
;
Meenakshi Verma
;
Harpreet
;
Achal Kumar Srivastava
;
Ritushree Kukreti
;
Arijit Mukhopadhyay
;
Nirmal Kumar Ganguly
;
Vibha Taneja
- Publication Type:Journal Article
- From:Neurology Asia
2014;19(4):367-374
- CountryMalaysia
- Language:English
-
Abstract:
Background & Objective: Transthyretin (TTR) has been associated with spinocerebellar ataxia (SCA)
by several independent case reports. Coexistence of TTR and SCA mutations, overlapping clinical
symptoms as well as altered levels of TTR in SCA patients suggest a correlation between TTR and
SCA. To our knowledge, no large cohort based study has been attempted to examine the association of
SCA with polymorphism in TTR gene. Here, we chose to investigate TTR variations in SCA patients
(n=266) and controls (n=192) of North Indian ethnicity. Methods: We sequenced the exons including
exon-intron boundaries of TTR gene in 55 patients and 55 controls. We observed four variations
which were further genotyped by single base extension method (SNaPshot) in a larger cohort (SCA
patients n=211 and controls n=137). Results: A novel synonymous variation c.372 C>G in exon 4
was detected in heterozygous condition in one control sample. We found nominal association for
rs1800458 (Gly6Ser), with SCA (p-value < 0.05) which did not remain after Bonferroni correction
for multiple tests. Pairwise linkage disequilibrium (LD) analysis revealed no LD between studied
SNPs. Further, we employed two-marker sliding window analysis and observed a weak association of
haplotype AT of rs1800458 and rs1667251 with SCA patients (p-value <0.05) which was not retained
after Bonferroni correction.
Conclusion: Our data suggests no association of genetic variations of TTR in SCA pathology.
- Full text:P020150630599417267022.pdf
