Department of Microbiology, Immunology and Biotechnology, School of Pharmacy and Biochemistry, University of Buenos Aires (UBA), Junín 956 (1113), Ciudad Autónoma de Buenos Aires, Argentina.
Nutr Metab Cardiovasc Dis. 2013 May;23(5):424-31. doi: 10.1016/j.numecd.2011.10.005. Epub 2012 Mar 6.
Specific Suppressor of Cytokine Signaling (SOCS) members, such as SOCS7, may play a role in the development of insulin resistance (IR) owing to their ability to inhibit insulin signaling pathways. The objective was to explore the association between common variants and related haplotypes in SOCS7 gene and metabolic traits related to obesity, lipid metabolism and IR.
780 unrelated men were included in a cross-sectional study. We selected three tagged SNPs that capture 100% of SNPs with minor allele frequency ≥ 0.10. Analyses were done separately for each SNP and followed up by haplotype analysis. rs8074124C was associated with both obesity (p = 0.005) and abdominal obesity (p = 0.002) and allele C carriers showed, in comparison with TT carriers, lower BMI (p = 0.001) and waist circumference (p = 0.001). rs8074124CC- carriers showed lower fasting insulin (p = 0.017) and HOMA-IR (p = 0.018) than allele T carriers. rs12051836C was associated with hypertriglyceridemia (p = 0.009) and hypertriglyceridemic waist (p = 0.006). rs12051836CC- carriers showed lower fasting insulin (p = 0.043) and HOMA-IR (p = 0.042). Haplotype-based association analysis (rs8074124 and rs12051836 in that order) showed associations with lipid and obesity -related phenotypes, consistent with single locus analysis. Haplotype analysis also revealed association between haplotype CT and both decreased HDL-C (p = 0.026) and HDL-C (p = 0.014) as a continuous variable.
We found, for the first time, significant associations between SOCS7 common variants and related haplotypes and obesity, IR and lipid metabolism disorders.
特定细胞因子信号转导抑制因子（SOCS）成员，如 SOCS7，可能由于其抑制胰岛素信号通路的能力而在胰岛素抵抗（IR）的发展中发挥作用。目的是探讨 SOCS7 基因中常见变异体及其相关单倍型与肥胖、脂质代谢和 IR 相关代谢特征之间的关系。
纳入了 780 名无血缘关系的男性进行横断面研究。我们选择了三个标记 SNP，它们捕获了最小等位基因频率≥0.10 的 100% SNP。分别对每个 SNP 进行分析，并进行单倍型分析。rs8074124C 与肥胖（p=0.005）和腹型肥胖（p=0.002）相关，与 TT 携带者相比，C 等位基因携带者的 BMI（p=0.001）和腰围（p=0.001）更低。rs8074124CC- 携带者的空腹胰岛素（p=0.017）和 HOMA-IR（p=0.018）低于 T 等位基因携带者。rs12051836C 与高三酰甘油血症（p=0.009）和高三酰甘油性腹型肥胖（p=0.006）相关。rs12051836CC- 携带者的空腹胰岛素（p=0.043）和 HOMA-IR（p=0.042）更低。基于单体型的关联分析（按照 rs8074124 和 rs12051836 的顺序）显示与脂质和肥胖相关表型相关，与单基因座分析一致。单体型分析还显示，单体型 CT 与 HDL-C 降低有关（p=0.026）和 HDL-C 呈连续变量（p=0.014）。
我们首次发现 SOCS7 常见变异体及其相关单体型与肥胖、IR 和脂质代谢紊乱之间存在显著关联。
