Genome wide association study of uric acid in Indian population and interaction of identified variants with Type 2 diabetes

被引：29

作者：

Giri, Anil K. ^{[1
,2
]}

Banerjee, Priyanka ^{[1
]}

Chakraborty, Shraddha ^{[1
,2
]}

Kauser, Yasmeen ^{[1
,2
]}

Undru, Aditya ^{[1
,2
]}

Roy, Suki ^{[1
]}

Parekatt, Vaisak ^{[1
]}

Ghosh, Saurabh ^{[3
]}

Tandon, Nikhil ^{[4
]}

Bharadwaj, Dwaipayan ^{[1
,2
,5
]}

机构：

[1] CSIR Inst Genom & Integrat Biol, Genom & Mol Med Unit, New Delhi 110020, India

[2] CSIR Inst Genom & Integrat Biol Campus, Acad Sci & Innovat Res, New Delhi 110020, India

[3] Indian Stat Inst, Human Genet Unit, Kolkata 700108, India

[4] All India Inst Med Sci, Dept Endocrinol & Metab, New Delhi 110029, India

[5] Jawaharlal Nehru Univ, Sch Biotechnol, New Delhi 110067, India

来源：

SCIENTIFIC REPORTS | 2016年 / 6卷

关键词：

TRANSPORTER SLC2A9; GENETIC-LOCI; RISK; GOUT; HYPERURICEMIA; METAANALYSIS; EXCRETION; EXERCISE; MELLITUS; TRAITS;

D O I：

10.1038/srep21440

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Abnormal level of Serum Uric Acid (SUA) is an important marker and risk factor for complex diseases including Type 2 Diabetes. Since genetic determinant of uric acid in Indians is totally unexplored, we tried to identify common variants associated with SUA in Indians using Genome Wide Association Study (GWAS). Association of five known variants in SLC2A9 and SLC22A11 genes with SUA level in 4,834 normoglycemics (1,109 in discovery and 3,725 in validation phase) was revealed with different effect size in Indians compared to other major ethnic population of the world. Combined analysis of 1,077 T2DM subjects (772 in discovery and 305 in validation phase) and normoglycemics revealed additional GWAS signal in ABCG2 gene. Differences in effect sizes of ABCG2 and SLC2A9 gene variants were observed between normoglycemics and T2DM patients. We identified two novel variants near long non-coding RNA genes AL356739.1 and AC064865.1 with nearly genome wide significance level. Meta-analysis and in silico replication in 11,745 individuals from AUSTWIN consortium improved association for rs12206002 in AL356739.1 gene to sub-genome wide association level. Our results extends association of SLC2A9, SLC22A11 and ABCG2 genes with SUA level in Indians and enrich the assemblages of evidence for SUA level and T2DM interrelationship.

引用

页数：9

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