Association of the Val66met polymorphism and risk of obesity, systematic review and meta-analysis

s from each of the records, we excluded 31 articles that were unrelated to val66met gene and 27 reports on disorders other than obesity. Another 20 reports were excluded as they were either reviews, meta-analyses, animal studies, and abstracts or being written in a language other than English. The total number of full-text articles, which were eligible for data extraction, was 30. Out of the 30 studies, 16 studies were excluded as they did not include reports on the association between Val66Met polymorphism (including genotype/allele frequency) and obesity. Further exclusion included studies in which the measure of association was either ambiguous (León-Mimila et al., 2013) or rejected by the software due to problematic confidence interval of the odds ratio (Timpano et al., 2011; Wu et al., 2010) or where the authors did not reply to our queries, leaving 11 eligible studies for the meta-analysis (Fig. 1). Characteristics of the participating studies The characteristics of individual studies are shown in Table 1. Most of the studies were conducted on adults except for four studies (Friedel et al., 2005; Ja’afaruSani et al., 2012; Skledar et al., 2012; Xi et al., 2011), which were conducted on adolescents. Participants in three of the studies were Asians (Hotta et al., 2009; Ja’afaruSani et al., 2012; Wang et al., 2011) and the rest were Caucasians and or Americans. Perkovic et al. (2013) reported data from three different time periods and were considered individually, while Beckers et al. (2008) reported data from a sample of female subjects. All studies had reported in frequency tables that allowed for computation of OR except (Thorleifsson et al., 2009) who only reported an adjusted OR. In total, 11 studies involving 13,153 individuals with obesity and 18,689 non-obese individuals were included in this analysis. Association of val66met and obesity The odds ratio of obesity for Val/Val versus Met carriers of the individual studies showed a wide variation. The overall pooled estimate (OR 0.9, 95%CI 0.793, 1.136) showed no significant association between Val66Met genotype and obesity. However, when studies were stratified according to age group, Val/Val genotype appeared as a risk factor for obesity among adults (OR 1.135, 95% CI =1.001, 1.286), while it was protective among adolescents (OR 0.61, 95% CI = 0.376, 0.984) (Figs. 2–4). Daher et al. / Journal of Applied Pharmaceutical Science 10 (1); 2020: 108-115 110 Figure 1. Flow diagram of study selection. Table 1. Characteristics of individual studies. Study name Year Country Study design n Mean age and SD BMI cut off value Hardy Weinberg equation IS indexed Obese Non-obese Obese Non-Obese 1 Ja’afaru Sani et al. 2012 Malaysia Cross sectional 132 432 14.85 ± 1.27 30 No deviation No 2 Marti et al. 2009 Spain Case control 159 154 42.4 ±10.5 38.6 ± 9.0 30 No deviation Yes Nikolac et al. 2013 Croatia Cohort 30 No deviation Yes 3 Nikolac et al. 1972 229 110 43.4 ± 4.4 4 Nikolac et al. 1982 275 64 53.4 ± 4.5 5 Nikolac et al. 2006 282 57 77.2 ± 4.5 6 Sustar et al. 2016 Croatia Case control 360 138 30 No deviation Yes 7 Morales-Marin et al. 2016 USA Cross sectional 79 60 36.29 ±14.37 30 Yes 8 Skeledar 2012 Croatia Cross sectional 74 226 10.78 ± 4.06 None No deviation yes 9 Friedel et al. 2004 Germany Case control 183 96 99th % No deviation yes 10 Hotta et al. 2009 Japan Case control 1127 1733 49.1±13.6 48.8±15.8 30 No deviation yes 11 Becker et al. 2008 Belgium Case control 532 197 37.5 ± 0.4 35.0 ± 0.6 30 No deviation yes 12 Thorleifsson et al. 2009 Iceland Genome wide association 5996 9255 51.47 (17.43) 30 No deviation Yes Netherlands 331 1432 58.43 (10.28) Denmark 949 2413 47.17 (8.73) European American 591 472 47.13 (12.52) African American 625 231 45.28 (11.75) 13 Xi et al. 2011 Chinese Cross sectional 1229 1619 11.8 (2.9) 12.5 (3.2) 95th % No deviation Yes Daher et al. / Journal of Applied Pharmaceutical Science 10 (1); 2020: 108-115 111 Heterogeneity and sensitivity analysis Table 2 shows heterogeneity statistics. The variance (Tau-squared) and the proportion of variation of true effect not attributed to random error (I2statistic) were higher for combined analysis. Nonetheless, the variance and I2 were reduced after stratification and were the lowest among studies on the adults. Moreover, omission of the study by Ja’afaruSani et al. (2012) substantially reduced heterogeneity and variance among adolescent studies. With respect to sensitivity analysis, although the 95% CI and p value have only minimally changed with the exclusion of some studies, the magnitude of OR was not appreciably affected (Table 3). Publication bias Funnel plot shows some asymmetry (Figs. 5–7) indicating some degree of publication bias. However, Begg’s and Egger’s p values were greater than 0.05.