ライフサイエンスコーパス: SLC30A8

1 enes: ESRP2, GBP1, TPP1, MAD2L1BP, GLUD2 and SLC30A8.

2 ently described associations at HHEX/IDE and SLC30A8.

3 sted (ANPEP, CAMK2B, HMG20A, KCNJ11, NOTCH2, SLC30A8, and WFS1), with significant AEI confirmed for f

4 560887 [G6PC2], rs4607517 [GCK], rs13266634 [SLC30A8], and rs10830963 [MTNR1B]) and weighting each SN

5 y showing that loss-of-function mutations in SLC30A8 are protective against diabetes.

6 s to the islet-specific Zn transporter ZnT8 (Slc30a8), as well as CD4 T cells, have been identified i

7 was likely due to effects of HLA-DQ2 and the SLC30A8 CC (RR) genotypes.

8 s) in 12 loci (e.g., TCF7L2, IDE/KIF11/HHEX, SLC30A8, CDKAL1, PKN2, IGF2BP2, FLJ39370, and EXT2/ALX4)

9 a lower frequency in the non-Swedes (37%) of SLC30A8 CT+TT (RW+WW) genotypes than in the Swedes (54%)

10 y, we generated mice with beta cell-specific Slc30a8 deficiency (ZnT8KO mice) and demonstrated an une

11 ted an unexpected functional linkage between Slc30a8 deletion and hepatic insulin clearance.

12 The impact of Slc30a8 deletion was examined in the context of the pure

13 tes that gender also modulates the impact of Slc30a8 deletion, though the physiological explanation a

14 ecific modifier genes modulate the impact of Slc30a8 deletion.

15 SLC30A8 encodes a zinc transporter ZnT8 largely restrict

16 SLC30A8 encodes zinc transporter-8 (ZnT8), which deliver

17 udies have previously identified variants in SLC30A8, encoding the zinc transporter ZnT8, associated

18 carrying rs13266634, a major risk allele of SLC30A8, exhibited increased insulin clearance, as asses

19 and replicated associations near HHEX and in SLC30A8 found by a recent whole-genome association study

20 al groups have examined the effect of global Slc30a8 gene deletion but the results have been highly v

21 The SLC30A8 gene encodes the islet-specific transporter ZnT-

22 e nucleotide polymorphism, rs13266634 in the SLC30A8 gene encoding the zinc transporter ZnT8, is asso

23 DKAL1, CDKN2A/CDKN2B, IGF2BP2, HHEX/IDE, and SLC30A8 gene regions.

24 Correspondingly, polymorphisms in the SLC30A8 gene, encoding the secretory granule Zn(2)(+) tr

25 tions in humans provide strong evidence that SLC30A8 haploinsufficiency protects against T2D, suggest

26 Ps) in or near genes (KCNJ11, PPARG, TCF7L2, SLC30A8, HHEX, CDKN2A/2B, CDKAL1, IGF2BP2, ARHGEF11, JAZ

27 ide association studies, variants in CDKAL1, SLC30A8, HHEX, EXT2, IGF2BP2, CDKN2B, LOC387761, and FTO

28 KN2B, and confirm that variants near TCF7L2, SLC30A8, HHEX, FTO, PPARG, and KCNJ11 are associated wit

29 A fourth cluster (TCF7L2, SLC30A8, HHEX/IDE, CDKAL1, CDKN2A/2B) was defined by loc

30 h patients due to different polymorphisms of SLC30A8, HLA-DQ, or both.

31 erve evidence that diabetes risk for CDKAL1, SLC30A8, IGF2BP2, and LOC387761 is specifically mediated

32 i including TCF7L2, HHEX-IDE, PPARG, KCNJ11, SLC30A8, IGF2BP2, CDKAL1, CDKN2A/2B, and JAZF1 with birt

33 AL1, CDKN2A/B, IGF2BP2, HHEX, LOC387761, and SLC30A8 in DPP participants and performed Cox regression

34 To investigate the role of Slc30a8 in the control of glucagon secretion, Slc30a8 wa

35 ci (CDKAL1, CDKN2A/B, HHEX-IDE, IGF2BP2, and SLC30A8) in 7,986 mothers and 19,200 offspring from four

36 s of solute carrier family 30 member 8 gene (SLC30A8) increase susceptibility to type 2 diabetes.

37 A polymorphic variant in SLC30A8 is associated with altered susceptibility to typ

38 Zinc transporter eight (SLC30A8) is a major target of autoimmunity in human type

39 Male C57BL/6J Slc30a8 knockout (KO) mice had normal fasting insulin le

40 enotypic heterogeneity was observed in mouse Slc30a8 knockouts.

41 In contrast, female C57BL/6J Slc30a8 KO mice had reduced ( approximately 20%) fasting

42 Neither male nor female C57BL/6J Slc30a8 KO mice showed impaired glucose tolerance.

43 rs observed in male mixed genetic background Slc30a8 KO mice.

44 idence for effect size heterogeneity for the SLC30A8 locus alone (RR(obese) 1.08 [1.01-1.15]; RR(nono

45 s at the solute carrier family 30, member 8 (SLC30A8) locus were nominally associated with decreased

46 sion of key beta cell genes, including Ins2, Slc30a8, MafA, Slc2a2, G6pc2, and Glp1r, was reduced aft

47 Our results indicate that SLC30A8 regulates hepatic insulin clearance and that gen

48 nteraction between total zinc intake and the SLC30A8 rs11558471 variant on fasting glucose levels (be

49 ), p=0.023]; [FTO (rs9939609), p=0.018] and [SLC30A8 (rs13266634), p=0.05].

50 ), p=0.004]; [IGF2BP2 (rs4402960), p=0.02]; [SLC30A8 (rs13266634), p=0.05]; [CAPN10 (rs2975760), p=0.

51 to type 2 diabetes was found for rs13266634 (SLC30A8), rs7923837 (HHEX), rs10811661 (CDKN2A/2B), rs44

52 The SLC30A8 SNP allele frequency (75% C and 25% T) varied li

53 Previous functional study of SLC30A8 suggested that reduced zinc transport increases

54 12, JAZF1, KCNQ1, LOC387761, MTNR1B, NOTCH2, SLC30A8, TCF7L2, THADA, and TSPAN8-LGR5.

55 ing via MAFA, PDX1, NKX6.1, PCSK1, PCSK2 and SLC30A8, thereby providing evidence for a coordinated re

56 Although common SLC30A8 variants, believed to reduce ZnT8 activity, incr

57 lc30a8 in the control of glucagon secretion, Slc30a8 was inactivated selectively in alpha-cells by cr

58 anking candidate, the zinc transporter ZnT8 (Slc30A8), was targeted by autoantibodies in 60-80% of ne

59 ified 12 rare protein-truncating variants in SLC30A8, which encodes an islet zinc transporter (ZnT8)

60 linkage between deleterious mutations in the SLC30A8 zinc transporter, which transports zinc into the

61 the glucose-raising effect of the rs11558471 SLC30A8 (zinc transporter) variant.

62 etes autoantigens, such as insulin, IA-2 and Slc30a8 (ZnT8).