Abstract
OBJECTIVE: To evaluate leptin level and its association with BMI and genetic predisposition in cases of early onset obesity. METHODS: 76 children (15.3 ± 10 yrs, 47 females) with morbid obesity (BMI of 41.7 ± 5.7 kg/m2) and 2 fathers and 5 mothers of these patients with BMI 47.8 ± 8.7 kg/m2 underwent genetic testing at the Prevention Genetics after obtaining consent. Leptin, Lipid profile, Glucose, Insulin, ALT, AST were measured. RESULTS: From 83 cases heterozygous polymorphism was found in 65 and in 18 genetic analysis was negative. | Patients were divided into 3 groups according to the leptin level. | 13 patients had leptin level less than 12 ng/ml (7.9 ± 2.5) (Group 1) (5 patients - no mutation, 8 with different combination of the genes: 1 with (BBS14 (CEP290) and BBS10), 2 BBS5, 2 SH2B1, 1 PLXNA3, 1 with (PCSK1 and ALMS1), 1 with BBS 20 (IFT172). Leptin didn't correlate with BMI in this group. | 6 patients had leptin elevated more than 50 ng/ml (74.5 ± 17.7) (Group 2). (1 patient – no mutation, 1 with KSR2, 1 with MCR4, 1 with SEMA3G, 1 with a combination of MCR4 and 2 different POMC, 1 with PLXNA4 and BBS15 (WDPCP). Leptin didn't correlate with BMI in this group. | 64 patients had leptin level (24.6 ± 9.4 ng/ml) expected for their BMI (42.7 ± 8.5 kg/m2) (Group 3). Leptin level correlated with BMI (r=0.37, P=0. 002). In group 3, Genetic analysis was negative in 12 patients, 1 gene was in 19 cases (KSR2 in 3, PCSK1 in 4, POMC in 2, others in 1: BBS 17(KZTFL1), BBS9, BBS21 (C8orf37), BBC20(IFT172), MCR4, MRAP2, PLXNA4, POMC, INPP5E, UCP3. | 2 genes in 25 cases: (BBS1, NTRK2), (BBS4, RAI1), (BBS4, PLXNA3) (BBS7, NTRK2), (BBS2, BBS9), (BBS9, MCR4),(BBS9, ADCY3), (BBS9, ALMS1), (BBS10, ALMS1), (BBS10, BBS22 (IFT74)), (BBS13 (MKS1), PCKS1), (BBS14 (CEP290), PCSK1), (BBS15 (WDPCP), PCSK1), (BBS18, POMC), (BBS20(IFT172), PCSK1), (BBS 22 (IFT74), SH2B1), (ALMS1,PCSK1), (ALMS1, BDNF), (SH2B1, NCOA1), (SH2B1, PCSK1), (SEMA3G, NTRK2), (SEMA3D, UCP3), (SIM1, NROB2), (KSR2, NTRK2), (MRAP2, RPGRIP1L). | 3 genes in 5 cases (BBS16 (SDCCAG8), BBS14 (CEP290), KIDINS220), (KSR2, ALMS1, PCNT), (KSR2, SEMA3G, NTRK2), (ALMS1, PCSK1, NCOA1), (BBS9, ALMS1, TRIM32)4 genes in 2 cases (BBS9, BBS11(TRIM32), ALMS1, POMC) and (BBS19 (IFT27), BBS 20 (IFT27), SEMA3B, PLXNA3). | 5 genes in 1 case (BBS12, BBS20 (IFT172), ALMS1, RPGRIP1L, SEMA3G). There were no differences in age, BMI, Hb A1c, SBP, DBP, Glucose, Insulin HOMA. ALT, AST, TG, and HDL levels between groups. CONCLUSION: There is a high frequency of genes involved in cilia regulation like BBS and ALMS1 genes. Identifying patients with low leptin level for the degree of obesity can individualize treatment to decrease appetite and increase energy expenditure Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.