Association of Single Nucleotide Polymorphisms in LEP, LEPR, and PPARG With Humoral Immune Response to Influenza Vaccine

Background: Although previous studies have proposed leptin plays an important role in energy metabolism as well as in immune response, the effects of leptin-related genes on influenza vaccine-induced immune response remain unexplored. In this study, we aimed to investigate the potential association...

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Main Authors: Mao Li, Hejiang Wei, Shuyi Zhong, Yanhui Cheng, Simin Wen, Dayan Wang, Yuelong Shu
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-10-01
Series:Frontiers in Genetics
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fgene.2021.725538/full
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author Mao Li
Hejiang Wei
Shuyi Zhong
Yanhui Cheng
Simin Wen
Dayan Wang
Yuelong Shu
author_facet Mao Li
Hejiang Wei
Shuyi Zhong
Yanhui Cheng
Simin Wen
Dayan Wang
Yuelong Shu
author_sort Mao Li
collection DOAJ
description Background: Although previous studies have proposed leptin plays an important role in energy metabolism as well as in immune response, the effects of leptin-related genes on influenza vaccine-induced immune response remain unexplored. In this study, we aimed to investigate the potential association of leptin gene (LEP), leptin receptor gene (LEPR), and peroxisome proliferator activated receptor gamma gene (PPARG) polymorphisms with humoral immune response to influenza vaccine.Methods: Based on the seroconversion to influenza vaccine, 227 low-responders and 365 responders were selected in this study, and 11 candidate single nucleotide polymorphisms (SNPs) were genotyped using the MassARRAY technology platform. Univariate and multivariate logistic regression analyses were used to explore the association of SNPs in LEP, LEPR, and PPARG with humoral immune response to influenza vaccine. We also conducted a stratified analysis by gender to further clarify this association. The haplotypes analysis was performed using SNPStats.Results: Significant differences were observed in the genotypic distribution of PPARG rs17793951 between the two groups (p = 0.001), and the PPARG rs17793951 AG + GG genotype was associated with a higher risk of low responsiveness to influenza vaccine adjusted for gender and age (additive genetic model: OR = 2.94, 95% CI = 1.67–5.19, dominant genetic model: OR = 2.81, 95% CI = 1.61–4.92). No significant association of other SNPs in LEP and LEPR with immune response to influenza vaccine was found. The stratified analysis found the gender difference in the association of LEPR and PPARG variants with immune response to influenza vaccine. We found that LEPR rs6673591 GA + AA genotype was correlated with low responsiveness to influenza vaccine only in males (OR = 1.96, 95% CI = 1.05–3.67), and PPARG rs17793951 AG + GG genotype was associated with low responsiveness to influenza vaccine in females (OR = 3.28, 95% CI = 1.61–6.67). Compared with the CGGAGGC haplotype composed of LEPR rs1327118, rs7602, rs1137101, rs1938489, rs6673591, rs1137100, and rs13306523, the CAAAAAC haplotype was positively correlated with immune response of influenza vaccine (OR = 0.34, 95% CI = 0.15–0.77). Haplotype TG comprised of PPARG rs796313 and rs17793951 was associated with a 2.85-fold increased risk of low responsiveness to influenza vaccine.Conclusion: Our study identified that PPARG rs17793951 variants were significantly associated with the immune response to influenza vaccine.
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spelling doaj.art-655b5eaff069466284824ca2b01d8c1a2022-12-21T21:56:48ZengFrontiers Media S.A.Frontiers in Genetics1664-80212021-10-011210.3389/fgene.2021.725538725538Association of Single Nucleotide Polymorphisms in LEP, LEPR, and PPARG With Humoral Immune Response to Influenza VaccineMao Li0Hejiang Wei1Shuyi Zhong2Yanhui Cheng3Simin Wen4Dayan Wang5Yuelong Shu6School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Guangzhou, ChinaNational Institute for Viral Disease Control and Prevention, Chinese Center for Disease Prevention and Control, Beijing, ChinaSchool of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Guangzhou, ChinaNational Institute for Viral Disease Control and Prevention, Chinese Center for Disease Prevention and Control, Beijing, ChinaSchool of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Guangzhou, ChinaNational Institute for Viral Disease Control and Prevention, Chinese Center for Disease Prevention and Control, Beijing, ChinaSchool of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Guangzhou, ChinaBackground: Although previous studies have proposed leptin plays an important role in energy metabolism as well as in immune response, the effects of leptin-related genes on influenza vaccine-induced immune response remain unexplored. In this study, we aimed to investigate the potential association of leptin gene (LEP), leptin receptor gene (LEPR), and peroxisome proliferator activated receptor gamma gene (PPARG) polymorphisms with humoral immune response to influenza vaccine.Methods: Based on the seroconversion to influenza vaccine, 227 low-responders and 365 responders were selected in this study, and 11 candidate single nucleotide polymorphisms (SNPs) were genotyped using the MassARRAY technology platform. Univariate and multivariate logistic regression analyses were used to explore the association of SNPs in LEP, LEPR, and PPARG with humoral immune response to influenza vaccine. We also conducted a stratified analysis by gender to further clarify this association. The haplotypes analysis was performed using SNPStats.Results: Significant differences were observed in the genotypic distribution of PPARG rs17793951 between the two groups (p = 0.001), and the PPARG rs17793951 AG + GG genotype was associated with a higher risk of low responsiveness to influenza vaccine adjusted for gender and age (additive genetic model: OR = 2.94, 95% CI = 1.67–5.19, dominant genetic model: OR = 2.81, 95% CI = 1.61–4.92). No significant association of other SNPs in LEP and LEPR with immune response to influenza vaccine was found. The stratified analysis found the gender difference in the association of LEPR and PPARG variants with immune response to influenza vaccine. We found that LEPR rs6673591 GA + AA genotype was correlated with low responsiveness to influenza vaccine only in males (OR = 1.96, 95% CI = 1.05–3.67), and PPARG rs17793951 AG + GG genotype was associated with low responsiveness to influenza vaccine in females (OR = 3.28, 95% CI = 1.61–6.67). Compared with the CGGAGGC haplotype composed of LEPR rs1327118, rs7602, rs1137101, rs1938489, rs6673591, rs1137100, and rs13306523, the CAAAAAC haplotype was positively correlated with immune response of influenza vaccine (OR = 0.34, 95% CI = 0.15–0.77). Haplotype TG comprised of PPARG rs796313 and rs17793951 was associated with a 2.85-fold increased risk of low responsiveness to influenza vaccine.Conclusion: Our study identified that PPARG rs17793951 variants were significantly associated with the immune response to influenza vaccine.https://www.frontiersin.org/articles/10.3389/fgene.2021.725538/fullinfluenza vaccinesingle nucleotide polymorphism (SNP)LEPLEPRPPARGimmune response
spellingShingle Mao Li
Hejiang Wei
Shuyi Zhong
Yanhui Cheng
Simin Wen
Dayan Wang
Yuelong Shu
Association of Single Nucleotide Polymorphisms in LEP, LEPR, and PPARG With Humoral Immune Response to Influenza Vaccine
Frontiers in Genetics
influenza vaccine
single nucleotide polymorphism (SNP)
LEP
LEPR
PPARG
immune response
title Association of Single Nucleotide Polymorphisms in LEP, LEPR, and PPARG With Humoral Immune Response to Influenza Vaccine
title_full Association of Single Nucleotide Polymorphisms in LEP, LEPR, and PPARG With Humoral Immune Response to Influenza Vaccine
title_fullStr Association of Single Nucleotide Polymorphisms in LEP, LEPR, and PPARG With Humoral Immune Response to Influenza Vaccine
title_full_unstemmed Association of Single Nucleotide Polymorphisms in LEP, LEPR, and PPARG With Humoral Immune Response to Influenza Vaccine
title_short Association of Single Nucleotide Polymorphisms in LEP, LEPR, and PPARG With Humoral Immune Response to Influenza Vaccine
title_sort association of single nucleotide polymorphisms in lep lepr and pparg with humoral immune response to influenza vaccine
topic influenza vaccine
single nucleotide polymorphism (SNP)
LEP
LEPR
PPARG
immune response
url https://www.frontiersin.org/articles/10.3389/fgene.2021.725538/full
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