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- Abu Seman, N (author)
Genetic and biological effects of sodium-chloride cotransporter (SLC12A3) in diabetic nephropathy
- Article/chapterEnglish2014
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- 2014-11-14
- S. Karger AG,2014
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- LIBRIS-ID:oai:prod.swepub.kib.ki.se:130302890
- http://kipublications.ki.se/Default.aspx?queryparsed=id:130302890URI
- https://doi.org/10.1159/000368916DOI
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- Language:English
- Summary in:English
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- <b><i>Background/Aims:</i></b> Solute carrier family 12 member 3 (<i>SLC12A3</i>) encodes a sodium/chloride transporter in kidneys. Previous reports suggest that Arg913Gln polymorphism in this gene is associated with diabetic nephropathy (DN), but the data appear to be inconsistent. Up to now, there is no biological evidence concerning the effects of <i>SLC12A3</i> in DN. In this study, we aim to evaluate the genetic effects of the <i>SLC12A3 </i>gene and its Arg913Gln polymorphism with genetic and functional analyses. <b><i>Methods:</i></b> We genotyped <i>SLC12A3</i> genetic polymorphisms including Arg913Gln in 784 non-diabetes controls and 633 type 2 diabetes (T2D) subjects with or without DN in a Malaysian population and performed a meta-analysis of the present and previous studies. We further analyzed the role of <i>slc12a3</i> in kidney development and progress of DN in zebrafish and db/db mice. <b><i>Results:</i></b> We found that <i>SLC12A3</i> Arg913Gln polymorphism was associated with T2D (p = 0.028, OR = 0.772, 95% CI = 0.612-0.973) and DN (p = 0.038, OR = 0.547, 95% CI = 0.308-0.973) in the Malaysian cohort. The meta-analysis confirmed the protective effects of <i>SLC12A3</i> 913Gln allele in DN (Z-value = -1.992, p = 0.046, OR = 0.792). Furthermore, with knockdown of zebrafish ortholog, <i>slc12a3 </i>led to structural abnormality of kidney pronephric distal duct at 1-cell stage. <i>Slc12a3</i> mRNA and protein expression levels were upregulated in kidneys of db/db mice from 6, 12, and 26 weeks at the age. <b><i>Conclusion:</i></b> The present study provided the first biological and further genetic evidence that <i>SLC12A3</i> has genetic susceptibility in the development of DN, while the minor 913Gln allele in this gene confers a protective effect in the disease. i 2014 S. Karger AG, Basel
Added entries (persons, corporate bodies, meetings, titles ...)
- He, BKarolinska Institutet (author)
- Ojala, JRMKarolinska Institutet (author)
- Mohamud, WNW (author)
- Ostenson, CGKarolinska Institutet (author)
- Brismar, KKarolinska Institutet (author)
- Gu, HFKarolinska Institutet (author)
- Karolinska Institutet (creator_code:org_t)
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- In:American journal of nephrology: S. Karger AG40:5, s. 408-4161421-96700250-8095
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