Association between CST3 rs2424577 polymorphism and corpulence related phenotypes during lifetime in populations of European ancestry

TY - JOUR

T1 - Association between CST3 rs2424577 polymorphism and corpulence related phenotypes during lifetime in populations of European ancestry

AU - Hooton, Henri

AU - Dubern, Beatrice

AU - Henegar, Corneliu

AU - Paternoster, Lavinia

AU - Nohr, Ellen A

AU - Alili, Rohia

AU - Rousseau, Francis

AU - Pelloux, Veronique

AU - Galan, Pilar

AU - Hercberg, Serge

AU - Arner, Peter

AU - Sørensen, Thorkild I A

AU - Clément, Karine

N1 - Copyright © 2011 S. Karger AG, Basel.

PY - 2011/4

Y1 - 2011/4

N2 - Objective: Cystatin C, a protein coded by CST3 gene, is implicated in adipose tissue biology. Our hypothesis is that common variants in CST3 gene could play a role in the development of corpulence during lifetime. Methods: Two tag SNPs were selected to capture all SNPs in the CST3 region. We first investigated the association of the two tag SNPs individually and combined into haplotypes with corpulence related phenotypes in 4,288 French subjects (BMI = 24.31 ( 3.74 kg/m2). Significant findings were replicated in five independent populations - 790 Danish lean men (BMI = 24.63 ( 2.30 kg/m 2), 672 Danish obese men (BMI = 33.23 ( 2.34 kg/m2), 763 Swedish women (BMI = 21.73 ( 2.87 kg/m2), 1,848 Danish lean women (BMI = 22.66 ( 2.85 kg/m2) and 2,061 Danish obese women (BMI = 37.01 ( 3.59 kg/m2). Results: Rs2424577 was associated with BMI in three independent populations - G/G carriers were less corpulent than A/A carriers in the French individuals (p = 0.045) and in the Danish lean men (p = 0.021), and they were more corpulent in the group of Swedish women (p = 0.004). This phenomenon has been described as a flip-flop phenomenon, probably caused by a multilocus effect. Conclusion: CST3 rs2424577 is associated with BMI in a complex fashion. This association is probably caused by the interaction between several functional variants.

AB - Objective: Cystatin C, a protein coded by CST3 gene, is implicated in adipose tissue biology. Our hypothesis is that common variants in CST3 gene could play a role in the development of corpulence during lifetime. Methods: Two tag SNPs were selected to capture all SNPs in the CST3 region. We first investigated the association of the two tag SNPs individually and combined into haplotypes with corpulence related phenotypes in 4,288 French subjects (BMI = 24.31 ( 3.74 kg/m2). Significant findings were replicated in five independent populations - 790 Danish lean men (BMI = 24.63 ( 2.30 kg/m 2), 672 Danish obese men (BMI = 33.23 ( 2.34 kg/m2), 763 Swedish women (BMI = 21.73 ( 2.87 kg/m2), 1,848 Danish lean women (BMI = 22.66 ( 2.85 kg/m2) and 2,061 Danish obese women (BMI = 37.01 ( 3.59 kg/m2). Results: Rs2424577 was associated with BMI in three independent populations - G/G carriers were less corpulent than A/A carriers in the French individuals (p = 0.045) and in the Danish lean men (p = 0.021), and they were more corpulent in the group of Swedish women (p = 0.004). This phenomenon has been described as a flip-flop phenomenon, probably caused by a multilocus effect. Conclusion: CST3 rs2424577 is associated with BMI in a complex fashion. This association is probably caused by the interaction between several functional variants.

U2 - 10.1159/000327797

DO - 10.1159/000327797

M3 - Journal article

SN - 1662-4025

VL - 4

SP - 131

EP - 144

JO - Obesity Facts

JF - Obesity Facts

IS - 2

ER -