[PAX4 gene polymorphism and islet autoantibody-negative ketosis-prone diabetes].
OBJECTIVE
To investigate PAX4 gene polymorphism and its association with islet autoantibody-negative patients with ketosis-prone diabetes in Chinese Han population.


METHODS
We screened the variation of exon 3 and 9 within PAX4 gene by denaturing high performance liquid chromatography(DHPLC) in 112 non-diabetes control subjects (NC group) and 141 patients with ketosis-prone diabetes (KPD group), who were both negative for glutamic acid decarboxylase antibody (GAD-Ab) as well as protein tyrosine phosphatase antibody (IA-2Ab). The sequences of abnormal peaks were analyzed by DNA-sequencing. The A1168C single nucleotide polymorphism in PAX4 gene was genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 308 non-diabetic control subjects and 141 KPD patients.


RESULTS
No variation was discovered in PAX4 gene exon 3 both in the patients and in the controls. There was a single nucleotide polymorphism locus A1168C in the PAX4 gene exon 9, which induced missence mutation P321H (rs712701). No significant difference was observed in the genotype and allele frequencies of A1168C polymorphism between KPD patients and control subjects (P=0.532, 0.426). The difference was detected in the CC genotype and C allele frequencies in the KPD group when patients were stratified by gender (P=0.009,0.028). According to age at diagnosis, the difference was observed in the CC genotype and C allele frequencies between <20 years old and > or = 20 years old in the KPD group (P=0.034,0.032). The level of FCP in the CC genotype group was significantly higher than that of FCP in AA genotype group (P=0.005).


CONCLUSIONS
A1168C polymorphism in PAX4 gene may not play an essential role in the genetic susceptibility of the islet autoantibody-negative KPD in Chinese Han population. However, A1168C variation may contribute to the predisposition to the male or < 20 years old patients with islet autoantibody-negative KPD.
Zhou
Min
M
Diabetic Center, Institute of Metabolism and Endocrinology, Central South University, Changsha 410011, China.
Zhang
Ying
Y
Zhang
Dongmei
D
Lin
Jian
J
Wang
Jianping
J
Zhou
Haifeng
H
Zhou
Zhiguang
Z
D000293:Adolescent; D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D001483:Base Sequence; D002648:Child; D003920:Diabetes Mellitus / Q000235:genetics* / Q000378:metabolism; D016883:Diabetic Ketoacidosis / Q000208:ethnology / Q000235:genetics* / Q000276:immunology; D005091:Exons; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D050417:Insulin-Secreting Cells / Q000276:immunology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D051761:Paired Box Transcription Factors / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
D001323:Autoantibodies; D018398:Homeodomain Proteins; C491709:PAX4 protein, human; D051761:Paired Box Transcription Factors