Association of single nucleotide polymorphism Rs2236518 in PRDM16 gene with BMI in Chinese males
Abstract
Hua YUE, Jin-wei HE, Yao-hua KE, Hao ZHANG, Chun WANG, Wei-wei HU, Jie-mei GU, Wen-zhen FU, Yun-qiu HU, Miao LI, Yu-juan LIU, Zhen-lin ZHANG*
Metabolic Bone Disease and Genetic Research Unit, Department of Osteoporosis and Bone Disease, Shanghai Jiao Tong University Affiliated the Sixth People’s Hospital, Shanghai 200233, China
Aim: PRD1-BF-1-RIZ1 homologous domain containing protein-16 (PRDM16) is a cell-autonomous transcriptional component that stimulates the development of brown fat cells. The aim of this study was to investigate the contribution of genetic variants of PRDM16 to obesity-related phenotype variations in Chinese.
Methods: A total of 3204 subjects (consisting of 400 male-offspring nuclear families, 401 female-offspring nuclear families, and 729 unrelated older males) were recruited. Ten tag single nucleotide polymorphisms (SNPs) within the PRDM16 gene were genotyped using multiplex quantitative real-time PCR by Taqman assay. Body compositions were measured by dual-energy X-ray absorptiometry (DXA). The associations of the SNPs with the obesity-related phenotypes were analyzed using the quantitative transmission disequilibrium test (QTDT), GLM-ANOVA and PLINK statistical methods.
Results: Rs2236518 was the only SNP that was associated with BMI in young (aged 20–40 years) males (P=0.011) using QTDT, and in the older men (aged 50–80 years) (P=0.003) using GLM-ANOVA. No significant associations were detected in the females. Nor was a relationship found between any haplotype and obesity-related phenotypes. When PLINK was used, no significant relationship was detected between 10 SNPs and obesity-related phenotypes in any of the studied cohorts.
Conclusion: Rs2236518 is associated with BMI in the young males (using QTDT), and the older males (using GLM-ANOVA). However, the result is not confirmed using PLINK. The discrepancy needs to be further addressed.
Keywords: PRD1-BF-1-RIZ1 homologous domain containing protein-16 (PRDM16); SNPs; obesity; BMI; brown adipose tissue; quantitative transmission disequilibrium test (QTDT); general linear model-ANOVA (GLM-ANOVA); PLINK; dual-energy X-ray absorptiometry; Chinese male
The study was supported by grants from the National Natural Science Foundation of China (No 81170803, 81070692, 81000360, and 30800387), Shanghai Rising-Star Program (No 11QA1404900), Shanghai Natural Science Foundation (No 11ZR1427300), and Academic Leaders in Health Sciences in Shanghai (No XBR2011014).
* To whom correspondence should be addressed.
E-mail ZZL2002@medmail.com.cn
Received 2012-10-10 Accepted 2012-12-24
Keywords:
Metabolic Bone Disease and Genetic Research Unit, Department of Osteoporosis and Bone Disease, Shanghai Jiao Tong University Affiliated the Sixth People’s Hospital, Shanghai 200233, China
Aim: PRD1-BF-1-RIZ1 homologous domain containing protein-16 (PRDM16) is a cell-autonomous transcriptional component that stimulates the development of brown fat cells. The aim of this study was to investigate the contribution of genetic variants of PRDM16 to obesity-related phenotype variations in Chinese.
Methods: A total of 3204 subjects (consisting of 400 male-offspring nuclear families, 401 female-offspring nuclear families, and 729 unrelated older males) were recruited. Ten tag single nucleotide polymorphisms (SNPs) within the PRDM16 gene were genotyped using multiplex quantitative real-time PCR by Taqman assay. Body compositions were measured by dual-energy X-ray absorptiometry (DXA). The associations of the SNPs with the obesity-related phenotypes were analyzed using the quantitative transmission disequilibrium test (QTDT), GLM-ANOVA and PLINK statistical methods.
Results: Rs2236518 was the only SNP that was associated with BMI in young (aged 20–40 years) males (P=0.011) using QTDT, and in the older men (aged 50–80 years) (P=0.003) using GLM-ANOVA. No significant associations were detected in the females. Nor was a relationship found between any haplotype and obesity-related phenotypes. When PLINK was used, no significant relationship was detected between 10 SNPs and obesity-related phenotypes in any of the studied cohorts.
Conclusion: Rs2236518 is associated with BMI in the young males (using QTDT), and the older males (using GLM-ANOVA). However, the result is not confirmed using PLINK. The discrepancy needs to be further addressed.
Keywords: PRD1-BF-1-RIZ1 homologous domain containing protein-16 (PRDM16); SNPs; obesity; BMI; brown adipose tissue; quantitative transmission disequilibrium test (QTDT); general linear model-ANOVA (GLM-ANOVA); PLINK; dual-energy X-ray absorptiometry; Chinese male
The study was supported by grants from the National Natural Science Foundation of China (No 81170803, 81070692, 81000360, and 30800387), Shanghai Rising-Star Program (No 11QA1404900), Shanghai Natural Science Foundation (No 11ZR1427300), and Academic Leaders in Health Sciences in Shanghai (No XBR2011014).
* To whom correspondence should be addressed.
E-mail ZZL2002@medmail.com.cn
Received 2012-10-10 Accepted 2012-12-24