Interaction of GCKR, MLXIPL and FADS Genes Polymorphisms with Obesity in the Occurrence of Childhood Metabolic Syndrome

Sedaghati-khayat

et al. 2020

Preprint

Background: Some previous studies reported that common functional variants (rs780093, rs780094, and rs1260326) in the glucokinase regulator gene (GCKR) were associated with metabolic syndrome despite the simultaneous association with the favorable and unfavorable metabolic syndrome components. We decided to examine these findings, to our knowledge for the first time, in Iranian adults. We investigated the association of the GCKR variants with incident MetS in mean follow-up times for nearly ten years.Methods: Analysis of this retrospective cohort study was performed among 5666 participants of the Tehran Cardiometabolic Genetics Study (TCGS) at 19-88 years at baseline. Linear and logistic regression analyses were used to investigate the metabolic syndrome (JIS criteria) association and its components with rs780093, rs780094, and rs1260326 in an additive genetic model. Cox regression was carried out to peruse variants' association with the incidence of metabolic syndrome in the TCGS cohort study.Results: In the current study, we have consistently replicated the association between the T-allele of GCKR SNPs and higher triglyceride levels and lower fasting blood sugar levels (p<0.05) in the Iranian population. The CT genotype of all three variants was associated with lower HDL-C levels. The proportional Cox adjusted model regression resulted that TT carriers of rs780094, rs780093, and rs1260326 were associated with 20%, 23%, and 21% excess risk metabolic syndrome incidence, respectively (p<0.05).Conclusions: Elevated triglyceride levels had the strongest association with GCKR selected variants among the metabolic syndrome components. Despite the association of these variants with decreased fasting blood sugar levels, T alleles of the variants were associated with metabolic syndrome incidence; so whether individuals are T allele carriers of the common functional variants, they have a risk factor for the future incidence of metabolic syndrome.

Section: Discussioncontrasting

confidence: 92%

Section: Discussionsupporting

confidence: 87%

GCKR Common Functional Polymorphisms are Associated with Metabolic Syndrome and its Components: A 10-Year Retrospective Cohort Study in Iranian Adults

Sedaghati-khayat

et al. 2020

Preprint

“…We consistently replicated previous GWAS results that reported the T allele carriers of selected variants had signi cant associations with lower FBS and higher TG levels among MetS components [17,18,20,[34][35][36][37]. Among Iranian studies, two studies in children and adolescents (CASPIAN III) have previously demonstrated the association between the rs780094 risk allele and higher triglyceride levels [38,39]. The correlation of rs1260326 and rs780094 with these MetS components has also been con rmed in our previous cross-sectional study in adults [27].…”

Section: Discussionsupporting

confidence: 89%

“…Based on our knowledge, the present study evaluated for the rst time the association of GCKR rs780093 with MetS risk and its components in an Iranian population; previous studies had focused on rs780094. The minor allele frequency (MAF) of the selected GCKR SNPs was different from the other Iranian population study [38]. This difference could be Because of the current study's greater sample size.…”

Section: Discussioncontrasting

confidence: 61%

GCKR Common functional polymorphisms are associated with metabolic syndrome and its components: a 10-year retrospective cohort study in Iranian adults

Sedaghati-khayat

et al. 2021

Preprint

Background Previous studies reported that common functional variants (rs780093, rs780094, and rs1260326) in the glucokinase regulator gene (GCKR) were associated with metabolic syndrome despite the simultaneous association with the favorable and unfavorable metabolic syndrome components. We decided to evaluate these findings in a cohort study with a large sample size of Iranian adult subjects, to our knowledge for the first time. We investigated the association of the GCKR variants with incident MetS in mean follow-up times for nearly ten years. Methods Analysis of this retrospective cohort study was performed among 5666 participants of the Tehran Cardiometabolic Genetics Study (TCGS) at 19–88 years at baseline. Linear and logistic regression analyses were used to investigate the metabolic syndrome (JIS criteria) association and its components with rs780093, rs780094, and rs1260326 in an additive genetic model. Cox regression was carried out to peruse variants' association with the incidence of metabolic syndrome in the TCGS cohort study. Results In the current study, we have consistently replicated the association of the GCKR SNPs with higher triglyceride and lower fasting blood sugar levels (p < 0.05) in Iranian adults. The CT genotype of the variants was associated with lower HDL-C levels. The proportional Cox adjusted model regression resulted that TT carriers of rs780094, rs780093, and rs1260326 were associated with 20%, 23%, and 21% excess risk metabolic syndrome incidence, respectively (p < 0.05). Conclusions Elevated triglyceride levels had the strongest association with GCKR selected variants among the metabolic syndrome components. Despite the association of these variants with decreased fasting blood sugar levels, T alleles of the variants were associated with metabolic syndrome incidence; so whether individuals are T allele carriers of the common functional variants, they have a risk factor for the future incidence of metabolic syndrome.

“…We consistently replicated previous GWAS results that reported the T allele carriers of selected variants had significant associations with lower FBS and higher TG levels among MetS components [ 22 , 23 , 25 , 39 – 42 ]. Among Iranian studies, two studies in children and adolescents (CASPIAN III) have previously demonstrated the association between the rs780094 risk allele and higher triglyceride levels [ 43 , 44 ]. The correlation of rs1260326 and rs780094 with these MetS components has also been confirmed in our previous cross-sectional study in adults [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

GCKR common functional polymorphisms are associated with metabolic syndrome and its components: a 10-year retrospective cohort study in Iranian adults

Sedaghati-Khayat

et al. 2021

Diabetol Metab Syndr

Background Previous studies reported that common functional variants (rs780093, rs780094, and rs1260326) in the glucokinase regulator gene (GCKR) were associated with metabolic syndrome despite the simultaneous association with the favorable and unfavorable metabolic syndrome components. We decided to evaluate these findings in a cohort study with a large sample size of Iranian adult subjects, to our knowledge for the first time. We investigated the association of the GCKR variants with incident MetS in mean follow-up times for nearly 10 years. Methods Analysis of this retrospective cohort study was performed among 5666 participants of the Tehran Cardiometabolic Genetics Study (TCGS) at 19–88 years at baseline. Linear and logistic regression analyses were used to investigate the metabolic syndrome (JIS criteria) association and its components with rs780093, rs780094, and rs1260326 in an additive genetic model. Cox regression was carried out to peruse variants’ association with the incidence of metabolic syndrome in the TCGS cohort study. Results In the current study, we have consistently replicated the association of the GCKR SNPs with higher triglyceride and lower fasting blood sugar levels (p < 0.05) in Iranian adults. The CT genotype of the variants was associated with lower HDL-C levels. The proportional Cox adjusted model regression resulted that TT carriers of rs780094, rs780093, and rs1260326 were associated with 20%, 23%, and 21% excess risk metabolic syndrome incidence, respectively (p < 0.05). Conclusions Elevated triglyceride levels had the strongest association with GCKR selected variants among the metabolic syndrome components. Despite the association of these variants with decreased fasting blood sugar levels, T alleles of the variants were associated with metabolic syndrome incidence; so whether individuals are T allele carriers of the common functional variants, they have a risk factor for the future incidence of metabolic syndrome.