Transthyretin gene mutation and expression in patients with familial vitreous amyloidosis_Chinese Journal of Ocular Fundus Diseases

Authors：

JiangMing ,  CaiShanjun , XieBing , 聂小梅 , 郑志涌 , 陈兴旺

Department of Ophthalmology, Affiliated Hospital of Zunyi Medical College, Zunyi 563003, China;

Corresponding author：

CaiShanjun, Email: caishanjun@163.com

Keywords：

Amyloidosis, familial/genetics; Thyroid hormones; DNA mutational analysis

DOI：

10.3760/cma.j.issn.1005-1015.2015.03.009

Video：

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Objective To observe the transthyretin (TTR) gene mutation, protein and mRNA expression in patients with familial vitreous amyloidosis. Methods Subjects were divided into three groups: (1) illness group: seven patients with familial vitreous amyloidosis. (2) No-illness group: 9 unaffected family members. (3) Control group: 9 healthy individuals in same area. Subjects' peripheral venous blood were collected and DNA were extracted, 4 exons of TTR gene were amplified by reverse transcription polymerase chain reaction(RT-PCR), the gene fragments were sequencing by the fluorescence labelling method. Serum TTR protein expression was detected by Western blot, and TTR mRNA in leukocyte was assayed by RT-PCR. Results 4 exons of TTR gene of all samples were amplified, and DNA sequencing data showed that 7 patients and 3 subjects DNA from unaffected family members had mutated in the 3rd exon of 107th base, changing from G to C. Heterozygous mutation occurred in codon of the 83th amino acid in exon 3, namely, Gly83Arg, resulted in the change of GGC to CGC. The protein and mRNA expression of TTR was lower in illness group than no-illness group and control groups(P < 0.05). Compared with control group, TTR mRNA expression in unaffected family members groups was significant decreased(P < 0.05). Conclusion Heterozygous mutation occurred in codon of the 83th amino acid in exon 3, namely Gly83Arg, and suggested that Gly83Arg is connected with the change of TTR mRNA and protein expression.

Citation： JiangMing, CaiShanjun, XieBing. Transthyretin gene mutation and expression in patients with familial vitreous amyloidosis. Chinese Journal of Ocular Fundus Diseases, 2015, 31(3): 248-251. doi: 10.3760/cma.j.issn.1005-1015.2015.03.009 Copy

1.	Ando E, Ando Y, Okamura R, et al. Ocular manifestations of familial amyloidotic polyneuropathy typeⅠ:long-term follow up[J]. Br J Ophthalmol, 1997, 81(4):295-298.
2.	Suhr OB, Lindqvist P, Olofsson BO, et al. Myocardial hypertrophy and function are related to age at onset in familial amyloidotic polyneuropathy[J]. Amyloid, 2006, 13(3):154-159.
3.	谢兵, 蔡善君, 蒋模, 等.家族性玻璃体淀粉样变性甲状腺激素结合蛋白Gly83Arg突变家系[J].中华眼底病杂志, 2013, 29(1):89-91.
4.	González-Duarte A, Lem-Carrillo M, Cárdenas-Soto K. Description of transthyretin S50A, S52P and G47A mutations in familial amyloidosis polyneuropathy[J]. Amyloid, 2013, 20(4):221-225.
5.	Falk RH, Comenzo RL, Skinner M. The systemic amyloidoses[J]. N Engl J Med, 1997, 337(13):898-909.
6.	Bulawa CE, Connelly S, Devit M, et al. Tafamidis, a potent and selective transthyretin kinetic stabilizer that inhibits the amyloid cascade[J]. Proc Natl Acad Sci USA, 2012, 109(24):9629-9634.
7.	Ferreira N, Santos SA, Domingues MR, et al. Dietary curcumin counteracts extracellular transthyretin deposition:insights on the mechanism of amyloid inhibition[J]. Biochim Biophys Acta, 2013, 1832(1):39-45.
8.	Hayashi Y, Mori Y, Yamashita S, et al. Potential use of lactosylated dendrimer (G3)/α-cyclodextrin conjugates as hepatocyte-specific siRNA carriers for the treatment of familial amyloidotic polyneuropathy[J]. Mol Pharm, 2012, 9(6):1645-1653.
9.	Su Y, Jono H, Torikai M, et al. Antibody therapy for familial amyloidotic polyneuropathy[J]. Amyloid, 2012, 19(Suppl 1):S45-46.
10.	陈凌燕, 吕林, 张平, 等.玻璃体淀粉样变性伴转甲蛋白Arg-83突变一例[J].眼科学报, 2008, 24(1):65-67.
11.	石一宁, 惠延年.玻璃体淀粉样变性一家系[J].中国实用眼科杂志, 1998(2):48.
12.	Russo M, Mazzeo A, Stancanelli C, et al. Transthyretin-related familial amyloidotic polyneuropathy:description of a cohort of patients with Leu64 mutation and late onset[J]. J Peripher Nerv Syst, 2012, 17(4):385-390.
13.	Jacobsson B, Collins VP, Grimelius L, et al. Transthyretin immunoreactivity in human and porcine liver, choroid plexus, and pancreatic islets[J]. J Histochem Cytochem, 1989, 37(1):31-37.
14.	Schreiber G, Aldred AR, Jaworowski A, et al. Thyroxine transport from blood to brain via transthyretin synthesis in choroid plexus[J]. Am J Physiol, 1990, 258(2 Pt 2):338-345.
15.	Saraiva MJ, Costa PP, Goodman DS. Studies on plasma transthyretin (prealbumin) in familial amyloidotic polyneuropathy, Portuguese type[J]. J Lab Clin Med, 1983, 102(4):590-603.
16.	Benson MD, Dwulet FE. Prealbumin and retinol binding protein serum concentrations in the Indiana type hereditary amyloidosis[J]. Arthritis Rheum, 1983, 26(12):1493-1498.
17.	Buxbaum J, Anan I, Suhr O. Serum transthyretin levels in Swedish TTR V30M carriers[J]. Amyloid, 2010, 17(2):83-85.

1. Ando E, Ando Y, Okamura R, et al. Ocular manifestations of familial amyloidotic polyneuropathy typeⅠ:long-term follow up[J]. Br J Ophthalmol, 1997, 81(4):295-298.
2. Suhr OB, Lindqvist P, Olofsson BO, et al. Myocardial hypertrophy and function are related to age at onset in familial amyloidotic polyneuropathy[J]. Amyloid, 2006, 13(3):154-159.
3. 谢兵, 蔡善君, 蒋模, 等.家族性玻璃体淀粉样变性甲状腺激素结合蛋白Gly83Arg突变家系[J].中华眼底病杂志, 2013, 29(1):89-91.
4. González-Duarte A, Lem-Carrillo M, Cárdenas-Soto K. Description of transthyretin S50A, S52P and G47A mutations in familial amyloidosis polyneuropathy[J]. Amyloid, 2013, 20(4):221-225.
5. Falk RH, Comenzo RL, Skinner M. The systemic amyloidoses[J]. N Engl J Med, 1997, 337(13):898-909.
6. Bulawa CE, Connelly S, Devit M, et al. Tafamidis, a potent and selective transthyretin kinetic stabilizer that inhibits the amyloid cascade[J]. Proc Natl Acad Sci USA, 2012, 109(24):9629-9634.
7. Ferreira N, Santos SA, Domingues MR, et al. Dietary curcumin counteracts extracellular transthyretin deposition:insights on the mechanism of amyloid inhibition[J]. Biochim Biophys Acta, 2013, 1832(1):39-45.
8. Hayashi Y, Mori Y, Yamashita S, et al. Potential use of lactosylated dendrimer (G3)/α-cyclodextrin conjugates as hepatocyte-specific siRNA carriers for the treatment of familial amyloidotic polyneuropathy[J]. Mol Pharm, 2012, 9(6):1645-1653.
9. Su Y, Jono H, Torikai M, et al. Antibody therapy for familial amyloidotic polyneuropathy[J]. Amyloid, 2012, 19(Suppl 1):S45-46.
10. 陈凌燕, 吕林, 张平, 等.玻璃体淀粉样变性伴转甲蛋白Arg-83突变一例[J].眼科学报, 2008, 24(1):65-67.
11. 石一宁, 惠延年.玻璃体淀粉样变性一家系[J].中国实用眼科杂志, 1998(2):48.
12. Russo M, Mazzeo A, Stancanelli C, et al. Transthyretin-related familial amyloidotic polyneuropathy:description of a cohort of patients with Leu64 mutation and late onset[J]. J Peripher Nerv Syst, 2012, 17(4):385-390.
13. Jacobsson B, Collins VP, Grimelius L, et al. Transthyretin immunoreactivity in human and porcine liver, choroid plexus, and pancreatic islets[J]. J Histochem Cytochem, 1989, 37(1):31-37.
14. Schreiber G, Aldred AR, Jaworowski A, et al. Thyroxine transport from blood to brain via transthyretin synthesis in choroid plexus[J]. Am J Physiol, 1990, 258(2 Pt 2):338-345.
15. Saraiva MJ, Costa PP, Goodman DS. Studies on plasma transthyretin (prealbumin) in familial amyloidotic polyneuropathy, Portuguese type[J]. J Lab Clin Med, 1983, 102(4):590-603.
16. Benson MD, Dwulet FE. Prealbumin and retinol binding protein serum concentrations in the Indiana type hereditary amyloidosis[J]. Arthritis Rheum, 1983, 26(12):1493-1498.
17. Buxbaum J, Anan I, Suhr O. Serum transthyretin levels in Swedish TTR V30M carriers[J]. Amyloid, 2010, 17(2):83-85.

Chinese Journal of Ocular Fundus Diseases

Transthyretin gene mutation and expression in patients with familial vitreous amyloidosis

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