Complex Copy Number Variation of AMY1 does not Associate with Obesity in two East Asian Cohorts. Issue 7 (28th April 2016)

• Record Type: Journal Article
• Authors: Yong, Rita Y.Y.; Mustaffa, Su'Aidah B.; Wasan, Pavandip S.; Sheng, Liang; Marshall, Christian R.; Scherer, Stephen W.; Teo, Yik‐Ying; Yap, Eric P.H.
• Is Part Of: Human mutation. Volume 37:Issue 7(2016)
• Page Start: 669
• Page End: 678
• Publication Date: 2016-04-28
• Subjects: amylase 1 -- AMY1 -- amylase 2A -- AMY2A -- copy number variation -- Chinese -- Malay -- obesity; Human chromosome abnormalities -- Periodicals; Mutation (Biology) -- Periodicals; 616.04205
• DOI: 10.1002/humu.22996
• Languages: English
• ISSNs: 1059-7794

Abstract

Abstract : The salivary amylase gene AMY1 harbours extensive copy number (CN) variation (CNV). By improving the resolution of CNV genotyping using quantitative PCR and digital PCR we discovered an unusual even:odd CN ratio in two East Asian populations (Chinese and Malay) studied, caused by the underlying haplotypic structure. With this high resolution CN genotyping method, we could not replicate the previously reported association between AMY1 and obesity. ABSTRACT: The human amylase gene locus at chromosome 1p21.1 is structurally complex. This region contains two pancreatic amylase genes, AMY2B, AMY2A, and a salivary gene AMY1 . The AMY1 gene harbors extensive copy number variation (CNV), and recent studies have implicated this variation in adaptation to starch‐rich diets and in association to obesity for European and Asian populations. In this study, we showed that by combining quantitative PCR and digital PCR, coupled with careful experimental design and calibration, we can improve the resolution of genotyping CNV with high copy numbers (CNs). In two East Asian populations of Chinese and Malay ethnicity studied, we observed a unique non‐normal distribution of AMY1 diploid CN genotypes with even:odd CNs ratio of 4.5 (3.3–4.7), and an association between the common AMY2A CN = 2 genotype and odd CNs of AMY1, that could be explained by the underlying haplotypic structure. In two further case–control cohorts ( n = 932 and 145, for Chinese and Malays, respectively), we did not observe the previously reported association between AMY1 and obesity or body mass index. Improved methods for accurately genotyping multiallelic CNV loci and understanding the haplotype complexity at the AMY1 locus are necessary for population genetics and association studies.