Single nucleotide polymorphisms of ADIPOQ gene associated with cardiovascular disease risk factors in European adolescents: the Healthy Lifestyle in Europe by Nutrition in Adolescence study

Abstract

Objectives: Cardiovascular diseases (CVDs) are responsible of 31% of all deaths worldwide. Genetic predisposition to CVDs in adolescents remains largely unknown.Aims of present research are to examine the association of ADIPOQ gene polymorphisms with cardiovascular disease risk factors in European adolescents. Methods: A total of 14 polymorphisms in the ADIPOQ gene were genotyped in 1.057 European adolescents (12-18 years old) from the Healthy Lifestyle in Europe by Nutrition in Adolescence Cross-Sectional Study. We measured serum lipids and a CVD risk score, along with weight, height, triceps and subscapular skinfold thickness, leptin, insulin and other markers of glucose regulation. Results: The rs822393, rs822395 and rs7649121 polymorphisms of ADIPOQ gene were significantly associated with several CVD risk factors (i.e., high-density lipoprotein cholesterol [HDL-C], Apolipoprotein (Apo) A1, systolic blood pressure and CVD risk Score) in European adolescents. We also found an association of the TGAAGT ADIPOQ haplotype (rs822393, rs16861210, rs822395, rs822396, rs12495941 and rs7649121) with HDL-C and ApoA1 levels. Conclusions: Several individual polymorphisms (rs822393, rs822395 and rs7649121) and a haplotype of ADIPOQ gene were significantly associated with cardiovascular disease risk factors in European adolescents.

Analysis of exome-sequenced UK Biobank subjects implicates genes affecting risk of hyperlipidaemia

“…These genes all have negative SLPs, suggesting that rare variants impacting their functioning might tend to be protective against hyperlipidaemia. ADIPOQ (SLP=-1.37) codes for adiponectin, an adipokine which is expressed in adipocytes which influences fat metabolism, and common variants in the gene are associated with cardiovascular disease risk and lipid levels (Liu et al, 2018;Salazar-Tortosa et al, 2020;Wang et al, 2019;Zhang et al, 2019). Adiponectin has a hypoglycaemic effect and can reverse the insulin resistance associated with both lipoatrophy and obesity (Berg et al, 2001;Yamauchi et al, 2001).…”

Dietary Intervention during 9 Months with a Hypocaloric Diet, Interaction of the Genetic Variant of Adiponectin Gene rs822393 with Metabolic Parameters

“…This genetic variant of the ADIPOQ gene presents scarce studies in the literature, and these studies have reported contradictory results. For example, the Healthy Lifestyle in Europe by Nutrition in Adolescents Study [ 8 ] has shown a strong association between rs822393 polymorphism, HDL-cholesterol, and APoA1 serum levels. Moreover, in a noninterventional design [ 21 ], a lack of association between this single nucleotide variant (SNV) and metabolic parameters was observed.…”

“…These differences in literature might be explained to the different ethnic groups or even the different ages of the patients (adolescents vs. adults), and finally, the presence of different allele frequencies and penetrance of this SNV in these populations. Moreover, this area of knowledge is of great interest because HDL-cholesterol has a clear relationship with cardiovascular events [ 22 ], and rs822393 variant is related with cardiovascular risk score, HDL-cholesterol, and systolic blood pressure [ 8 ], too.…”

“…One common genetic variant rs822393 (-4522C/T) is located in the proximal promoter region of the ADIPOQ gene. This SNV rs822393 regulates adiponectin promoter activity, and it is related with low circulating levels of adiponectin and insulin sensitivity [ 7 , 8 ]. In addition, this SNV has been associated with an increase in the risk of diabetes mellitus [ 9 ].…”