AUTHOR=Zhang Youjin , Chen Lvlin , Zhu Junchen , Liu Hao , Xu Luying , Wu Yang , He Chuan , Song Yongyan 

TITLE=Minor alleles of FTO rs9939609 and rs17817449 polymorphisms confer a higher risk of type 2 diabetes mellitus and dyslipidemia, but not coronary artery disease in a Chinese Han population

JOURNAL=Frontiers in Endocrinology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2023.1249070

DOI=10.3389/fendo.2023.1249070

ISSN=1664-2392

ABSTRACT=<sec><title>Background</title><p>Relationships of the polymorphisms in fat mass and obesity-associated gene (<italic>FTO</italic>) and peroxisome proliferator-activated receptor delta gene (<italic>PPARD</italic>) with metabolic-related diseases remain to be clarified.</p></sec><sec><title>Methods</title><p>One thousand three hundred and eighty-one subjects were enrolled. Metabolic-related diseases including obesity, dyslipidemia, hyperhomocysteinemia, hyperuricemia, hypertension, type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD) were defined based on diagnostic criteria. <italic>FTO</italic> rs9939609 and rs17817449, and <italic>PPARD</italic> rs2016520 and rs2267668 polymorphisms were genotyped by using polymerase chain reaction-restricted fragment length polymorphism method.</p></sec><sec><title>Results</title><p>Patients with T2DM or dyslipidemia had a higher frequency of AA, AT or AA + AT genotypes as well as A allele of <italic>FTO</italic> rs9939609 polymorphism than those free of T2DM or dyslipidemia (<italic>P</italic> ≤ 0.04 for all). Patients with T2DM or dyslipidemia had a higher frequency of GG, GT or GG + GT genotypes as well as G allele of <italic>FTO</italic> rs17817449 polymorphism than those free of T2DM or dyslipidemia (<italic>P</italic> ≤ 0.03 for all). Multivariate logistic regression analyses showed that <italic>FTO</italic> rs9939609 and rs17817449 polymorphisms were independently associated with T2DM as well as dyslipidemia after adjustment for age, sex, smoking and other metabolic diseases. <italic>FTO</italic> rs9939609 and rs17817449 polymorphisms were not associated with obesity, hyperhomocysteinemia, hyperuricemia, hypertension and CAD. Obese or T2DM carriers of the AA or AT genotype of the <italic>FTO</italic> rs9939609 polymorphism had a higher prevalence of dyslipidemia compared to non-obese or non-T2DM carriers of the AA or AT genotype (<italic>P</italic> = 0.03 for both). Among the carriers of GG or GT genotype of the <italic>FTO</italic> rs17817449 polymorphism, the prevalence of dyslipidemia in obese patients was higher than that in non-obese subjects (<italic>P</italic> &lt; 0.01). <italic>PPARD</italic> rs2016520 and rs2267668 polymorphisms were not correlated with any of the metabolic-related diseases in the study population.</p></sec><sec><title>Conclusion</title><p>Minor alleles of <italic>FTO</italic> rs9939609 and rs17817449 polymorphisms confer a higher risk of T2DM and dyslipidemia, and the risk is further increased among obese individuals. <italic>PPARD</italic> rs2016520 and rs2267668 polymorphisms are not associated with metabolic-related diseases.</p></sec>