Open AccessGenome-wide linkage analysis and regional fine mapping identified variants in the RYR3 gene as a novel quantitative trait locus for circulating adiponectin in Chinese population
Author(s) -
YiCheng Chang,
Yen-Feng Chiu,
ChihTsueng He,
Wayne HueyHerng Sheu,
MingWei Lin,
Todd B. Seto,
Themistocles L. Assimes,
Yuh–Shan Jou,
L. H. Su,
WeiJei Lee,
PoChu Lee,
Shu-Huei Tsai,
LeeMing Chuang
Publication year - 2016
Publication title -
medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 148
eISSN - 1536-5964
pISSN - 0025-7974
DOI - 10.1097/md.0000000000005174
Subject(s) - adiponectin , single nucleotide polymorphism , haplotype , locus (genetics) , genetics , population , genome wide association study , quantitative trait locus , medicine , genetic association , biology , insulin resistance , allele , gene , insulin , genotype , environmental health
Adiponectin is adipocyte-secreted cytokine with potent insulin-sensitizing action in peripheral tissues. The heritability of plasma adiponectin is high in Han Chinese population. To identify genetic loci influencing plasma adiponectin levels in Chinese population, we performed a genome-wide linkage scan in 1949 Chinese participants of the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance family study and mapped a quantitative trail locus located on chromosome 15 at 31 cM (logarithm of odds = 3.04) with 1-logarithm of odds support interval at 24 to 34 cM. Within this mapped region, we further genotyped a total of 68 single-nucleotide polymorphisms in 12 genes. Association analysis revealed that haplotypes composed of single-nucleotide polymorphisms in the ryanodine receptor 3 ( RYR3 ) gene had strongest association with plasma adiponectin. RYR3 haplotypes were also associated with systolic ( P = 0.001) and diastolic ( P = 7.1 × 10 −4 ) blood pressure and high-density lipoprotein cholesterol ( P = 1.4 × 10 −4 ). Furthermore, an inverse relationship between expression of RYR3 and adiponectin was observed in human abdominal adipose tissue. In conclusion, a genome-wide linkage scan and regional association fine-mapping identified variants in the RYR3 gene as a quantitative trail locus for plasma adiponectin levels in Chinese population.