Genetic variants of human urea transporter-2 are associated with metabolic syndrome in Asian population.
BACKGROUND
A previous study has reported that the Ile227 and Ala357 genetic variants of human urea transporter-2 (HUT2) were associated with blood pressure in males in Asian population. In this study, we aimed to investigate five known HUT2 genetic variants with metabolic syndrome (MetS) and its related traits in the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance (SAPPHIRe) study cohort.


METHODS
Five HUT2 single nucleotide polymorphisms (SNPs) were selected and genotyped among 1791 subjects in the SAPPHIRe study cohort. We first computed allele frequency and performed Hardy-Weinberg equilibrium (HWE) test in controls for each SNP. Next, we tested genotype associations with metabolic syndrome using multiple generalized estimating equations (GEE) models with covariate adjustment. Furthermore, multi-marker and multi-trait association tests were carried out using FBAT program. To account for multiple testing, Bonferroni correction was applied in this study.


RESULTS
Among those 5 HUT2 SNPs, SNPs 1, 2 and 3 were significantly associated with MetS in the total sample and females, separately (9×10(-4)≤p≤0.04), but only the association between SNP 1 and MetS in females remained statistically significant after Bonferroni correction. When testing 5 SNPs simultaneously, significant associations were found with triglycerides (TG) (p=0.04). Likewise, significant multi-trait association (combining the data of waist circumference, TG, high density lipoprotein (HDL) cholesterol and fasting glucose together) was found with SNP 2 (p=0.04), but both results of multi-maker and multi-trait associations did not remain significant after multiple testing correction.


CONCLUSIONS
The results have provided evidence that the HUT2 gene may play a certain role in developing MetS and its related traits in Asian population. Further investigation of the HUT2 gene influencing MetS and its related traits will be warranted.
Tsai
Hui-Ju
HJ
Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, Zhunan, Taiwan.
Hsiao
Chin-Fu
CF
Ho
Low-Tone
LT
Chuang
Lee-Ming
LM
He
Chih-Tsueng
CT
Curb
J David
JD
Quertermos
Thomas
T
Hsiung
Chao A
CA
Sheu
Wayne H-H
WH
D000704:Analysis of Variance; D044466:Asian People / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D024821:Metabolic Syndrome / Q000235:genetics*; D008875:Middle Aged; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D000096982:Urea Transporters
D005819:Genetic Markers; D026901:Membrane Transport Proteins; D000096982:Urea Transporters