Effects of FTO RS9939906 and MC4R RS17782313 on obesity, type 2 diabetes mellitus and blood pressure in patients with hypertension

Abstract

BackgroundGenetic variants of the FTO gene rs9939609 A/T and the MC4R gene rs17782313 C/T have been associated with obesity. Individuals with mutations in MC4R gene have lower blood pressure (BP), independently of obesity. This study aimed to investigate the association of FTO rs9939609 and MC4R rs17782313 with anthropometric indexes, BP, and type 2 diabetes mellitus among hypertensive patients.MethodsWe genotyped 217 individuals (86 men and 131 women) with hypertension (systolic or diastolic BP ≥ 140/90 mmHg or using antihypertensive drugs). Diabetes mellitus was diagnosed according to the American Diabetes Association criteria. Waist and neck circumferences (cm), Body Adiposity Index (BAI,%), Lipid Accumulation Product Index (LAP, cm.mmol.l) and body mass index (BMI, kg/m2) were analyzed using analysis of covariance or modified Poisson’s regression.ResultsRare allele frequencies were 0.40 for A for FTO rs9939609 and 0.18 for C for MC4R rs17782313. A positive association of FTO rs9939609 and MC4R rs17782313 with BMI was observed in the overall sample. Among men and women, neck circumference was associated with the FTO genotype and, for women, MC4R genotype. In contrast, in men we found a negative association of MC4R rs17782313 with diastolic BP (TT 90.1 ±12.2, TC/CC 83.2 ±12.1; P = 0.03) and borderline association for systolic BP after controlling for age and BMI.ConclusionsCommon genetic variants of FTO rs9939609 have positive associations with BMI and neck circumference and MC4R rs17782313 in women, but a negative association with diastolic and mean blood pressure in men with hypertension.

Relationships between <em>FTO</em> rs9939609, <em>MC4R</em> rs17782313, and <em>PPAR&gamma;</em> rs1801282 polymorphisms and the occurrence of selected metabolic and hormonal disorders in middle-aged and elderly men &ndash; a preliminary study

“…With regard to MetS, the studied association with the MC4R rs17782313 polymorphism disappears after adjusting for WC, indicating that the association with MetS is driven by the association with this factor 22. Moreover, studies on males proved that the rs17782313 polymorphism is associated with lower HDL concentration23 and elevated DBP 14,24…”

Association of melanocortin 4 receptor gene variation with satiation and gastric emptying in overweight and obese adults

“…Conversely, the MC4R V103I and I251L polymorphisms are associated with reduced risk of obesity. The polymorphism rs17782313, mapped 188 kb downstream from MC4R, is strongly associated with obesity and higher body mass index (BMI) (Frayling et al 2007;Loos et al 2008;Vogel et al 2011) alone or in association with other obesity-related genes, such as FTO (Marcadenti et al 2013). A GWAS study of 60,000 adults indicated that rs17782313(C) alleles are associated with higher BMI, with even greater effect in children.…”

Association of KALRN, ADIPOQ, and FTO gene polymorphism in type 2 diabetic patients with coronary artery disease

“…FTO rs9939609 are strongly associated with obesity and T2D [29]. T2D, insulin resistance, and hypertension as cardiovascular risk factors were associated with the risk allele A for FTO rs9939609 [13].…”

“…Li et al [29] reported that FTO is associated with an increased risk of obesity and T2D, and FTO association with T2D is independent of BMI. Finally, Marcadenti et al [13] reported that common genetic variants of FTO rs9939609 have positive associations with BMI in women, but a negative association with diastolic and mean blood pressure in men with hypertension.…”

“…The FTO gene was identified in chromosome 16q12.2 and is strongly expressed in the hypothalamus, which is involved in the control of energy homeostasis and regulation of blood pressure [13,14].…”