Strong Gender-Specific Additive Effects of the NYD-SP18 and FTO Variants on BMI Values

Abstract

The role of the FTO gene in obesity development is well established in populations around the world. The NYD-SP18 variant has been suggested to have a similar effect on BMI, but the role of this gene in determining BMI has not yet been verified. The objective of our study was to confirm the association between NYD-SP18 rs6971019 SNP and BMI in the Slavic population and to analyze i) the gender-specific effects of NYD-SP18 on BMI and ii) the simultaneous effect of FTO rs17817449 and NYD-SP18 on BMI. We analyzed a sample of a large adult population based on the post-MONICA study (1,191 males and 1,368 females). Individuals were analyzed three times over 9 years. NYD-SP18 rs6971019 SNP is related to BMI in males (2000/1 GG 28.3±3.7 kg/m 2 vs. +A 27.5±3.7 kg/m 2 P<0.0005; in other examinations P<0.05 and <0.005), but not in females (all P values over 0.48 in all three examinations). Further analysis revealed the significant additive effect (but not the interaction) of FTO and NYD-SP18 SNPs on BMI in males (all P<0.01). These results suggest that association between NYD-SP18 rs6971019 SNP and BMI may be restricted to males.Furthermore, variants within NYD-SP18 and FTO genes revealed a significant additive effect on BMI values in males.

Lack of Association between <b><i>NYD-SP18</i></b> Variant and Obesity. The Health Alcohol and Psychosocial Factors in Eastern Europe Study

“…For instance, Lithuanians had the highest mean age and the highest mean BMI (both p values <0.001). The genotype (allele) distributions were similar across the countries; the overall allele distribution (with minor A allele frequency of 26%) were also similar to the distribution reported previously (frequency of the minor allele 23%) [ 5 , 7 ]. In our study, both overall and within each cohort, the rs6971091 polymorphism was not associated with BMI values; all p values were >0.45 in codominant models (table 1 ).…”

“…The primary report [ 5 ] found the association with obesity in two independent population samples; however, the relatively small sample size in these studies (several hundred individuals in each sample) makes them prone to false positive results. More recently, the association has been detected in males, but not in females, in the Czech post-MONICA study [ 7 ]. The possible role of the NYD-SP18 in the determination of BMI has been further suggested in a small intervention study [ 8 ] of overweight non-diabetic females; the results suggest that common homozygotes profit more from the intensive life style intervention than carriers of the minor A allele.…”

“…The authors reported an effect of the NYD-SP18 variants on obesity that was even larger than the effect of the FTO polymorphism [ 5 ]. More recently, the association between the rs697109 SNP and BMI was confirmed in males, but not in females [ 7 ]. In addition, the additive effect between this SNP and 1st intron polymorphism of the FTO gene on BMI values has been detected [ 7 ].…”

“…More recently, the association between the rs697109 SNP and BMI was confirmed in males, but not in females [ 7 ]. In addition, the additive effect between this SNP and 1st intron polymorphism of the FTO gene on BMI values has been detected [ 7 ]. Finally, a small intervention study in females suggested that NYD-SP18 polymorphism could be a significant predictor of positive body composition changes after a short-term intensive life style intervention [ 8 ].…”

Polygenic Hypercholesterolemia: Examples of GWAS Results and Their Replication in the Czech-Slavonic Population

“…We examined one group of adults (1,191 males and 1,368 females, aged 25-64 years; mean age of 49.0±10.7 years) (Hubacek et al 2009, Hubacek et al 2015a. The individuals had participated in the post-MONICA study (Cifkova et al 2010) and were selected according to the WHO MONICA project protocol (Tunstall-Pedoe et al 2003), which was designed to examine the risk factors of cardiovascular disease development, including plasma lipids.…”