Mutation analysis of SLC5A2 gene and determination of the renal threshold for glucose excretion in Chinese patients with familial renal glucosuria
10.3760/cma.j.issn.1001?7097.2018.11.003
- VernacularTitle:中国家族性肾性糖尿SGLT2基因突变分析及肾葡萄糖阈值的测定
- Author:
Sai WANG
1
;
Xuemei LIU
;
Xiangzhong ZHAO
;
Chunmei LI
;
Ruixiao ZHANG
;
Leping SHAO
Author Information
1. 266003,青岛大学附属医院肾脏科
- Keywords:
Glucosuria;
Renal;
DNA mutational analysis;
Genotype;
SGLT2 gene;
Renal threshold of glucose excretion
- From:
Chinese Journal of Nephrology
2018;34(11):816-821
- CountryChina
- Language:Chinese
-
Abstract:
Objective To analyze and identify the mutations in SGLT2 gene of nine Chinese families with FRG, and determine the renal threshold for glucose excretion (RTG), so as to explore the association of genotype and RTG. Methods All coding regions of SGLT2 gene, including intron exon boundaries, were analyzed using PCR followed by direct sequence analysis. Quantitative test for 24?hour urine glucose and RTG were measured among 9 probands (21 patients) and their family members from 9 pedigrees (total 25 subjects). The differences in renal glucose thresholds between patients with different genotypes (heterozygotes and compound heterozygotes; c.886(-10_-31) del heterozygotes and other heterozygotes) were compared. Results Twelve mutations were identified by SGLT2 gene analysis, including 10 novel ones that were not included in HGMD:c.331T>C, p.W111R;c.374T>C, p.M125T; c.394C>T, p.R132C; c.612G>C, p.Q204H; c.829C>T, p.P277S; c.880G>A, p.D294N;c.1129G>A, p.G377S; c.1194C>A, p.F398L; c.1540C>T, p.P514S; c.1573C>T, p.H525Y. In thisstudy, the mutation c.886(-10_-31)del that is specific to Chinese population accounted for about 28％of the total alleles (5/18). The RTG values of patients with compound heterozygous mutations were much lower than those with simple heterozygous mutations [(1.28 ±0.10) vs (5.14±0.77) mmol/L; P<0.001];and c.886(-10_-31)del heterozygotes had significant lower RTG values than others [(4.43 ± 0.37) vs (5.70 ± 0.51) mmol/L, P<0.001]. Conclusions Ten novel mutations which may be related to FRG are found in this study, and c.886(-10-31)del may be a hot?spot mutation in Chinese patients. Compound heterozygotes had much lower RTG values than simple heterozygotes.
