Relation of resistin gene variants to resistin plasma levels and altered susceptibility to polycystic ovary syndrome: A case control study

Background A role for resistin in the pathogenesis of polycystic ovarian syndrome (PCOS) and related features were described for various ethnicities. As its expression is partly inherited, a role for RETN polymorphisms in regulating resistin levels and PCOS risk was shown, but with varied results. A...

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Veröffentlicht in:American journal of reproductive immunology (1989) 2023-07, Vol.90 (1), p.e13731-n/a
Hauptverfasser: Al‐Awadi, Aminah M., Saldhana, Fabiola Lisa, Bauyrzhanova, Zhansaya, Nemr, Rita, Mahmood, Naeema A., Almawi, Wassim Y.
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container_issue 1
container_start_page e13731
container_title American journal of reproductive immunology (1989)
container_volume 90
creator Al‐Awadi, Aminah M.
Saldhana, Fabiola Lisa
Bauyrzhanova, Zhansaya
Nemr, Rita
Mahmood, Naeema A.
Almawi, Wassim Y.
description Background A role for resistin in the pathogenesis of polycystic ovarian syndrome (PCOS) and related features were described for various ethnicities. As its expression is partly inherited, a role for RETN polymorphisms in regulating resistin levels and PCOS risk was shown, but with varied results. Aim To investigate the association of rs34124816 (–537A>C), rs1862513 (–420C>G), rs3219175 (–358G>A), rs3745367 (+299G>A), rs3745369 (+1263G>C), and rs1423096 (+4965C>T) RETN SNPs with PCOS. Methods Study subjects included 583 women with PCOS, and 713 eumenorrheic women serving as controls. Genotyping was done by real‐time PCR. Results Higher minor allele frequency (MAF) of rs34124816, rs3219175, and rs3745369, and lower MAF of rs1862513 and rs1423096 were seen in PCOS cases. Reduced PCOS risk was found with rs3745367 minor‐allele homozygotes and rs1423096 minor‐allele homozygotes, while increased risk was linked with rs3745367 heterozygotes, and with rs3745369 heterozygotes and minor‐allele homozygotes. While it did not reach statistical significance, serum resistin levels were elevated in PCOS cases than in control women and major‐allele homozygotes of rs34124816 and rs1862513, and in rs1423096 minor‐allele‐containing carriers. Carriage of rs34124816 correlated positively with age and LH, whereas rs1862513 positively and rs3745367 negatively correlated with fasting glucose. Six‐locus (rs34124816‐rs1862513‐rs3219175‐rs3745367‐rs3745369‐rs1423096) haplotype analysis demonstrated a significant reduction in AGGGGG and a marked increase in AGGGCG haplotypes between cases and controls, thus assigning PCOS protective and susceptible nature to these haplotypes, respectively. Conclusions This study is the first to document the contribution of rs34124816 and rs1423096 RETN variants to the risk of PCOS. The varied association of RETN gene variants with PCOS suggests an ethnic contribution of RETN association with PCOS.
doi_str_mv 10.1111/aji.13731
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As its expression is partly inherited, a role for RETN polymorphisms in regulating resistin levels and PCOS risk was shown, but with varied results. Aim To investigate the association of rs34124816 (–537A&gt;C), rs1862513 (–420C&gt;G), rs3219175 (–358G&gt;A), rs3745367 (+299G&gt;A), rs3745369 (+1263G&gt;C), and rs1423096 (+4965C&gt;T) RETN SNPs with PCOS. Methods Study subjects included 583 women with PCOS, and 713 eumenorrheic women serving as controls. Genotyping was done by real‐time PCR. Results Higher minor allele frequency (MAF) of rs34124816, rs3219175, and rs3745369, and lower MAF of rs1862513 and rs1423096 were seen in PCOS cases. Reduced PCOS risk was found with rs3745367 minor‐allele homozygotes and rs1423096 minor‐allele homozygotes, while increased risk was linked with rs3745367 heterozygotes, and with rs3745369 heterozygotes and minor‐allele homozygotes. While it did not reach statistical significance, serum resistin levels were elevated in PCOS cases than in control women and major‐allele homozygotes of rs34124816 and rs1862513, and in rs1423096 minor‐allele‐containing carriers. Carriage of rs34124816 correlated positively with age and LH, whereas rs1862513 positively and rs3745367 negatively correlated with fasting glucose. Six‐locus (rs34124816‐rs1862513‐rs3219175‐rs3745367‐rs3745369‐rs1423096) haplotype analysis demonstrated a significant reduction in AGGGGG and a marked increase in AGGGCG haplotypes between cases and controls, thus assigning PCOS protective and susceptible nature to these haplotypes, respectively. Conclusions This study is the first to document the contribution of rs34124816 and rs1423096 RETN variants to the risk of PCOS. The varied association of RETN gene variants with PCOS suggests an ethnic contribution of RETN association with PCOS.</description><identifier>ISSN: 1046-7408</identifier><identifier>EISSN: 1600-0897</identifier><identifier>DOI: 10.1111/aji.13731</identifier><identifier>PMID: 37382171</identifier><language>eng</language><publisher>Denmark: Wiley Subscription Services, Inc</publisher><subject>Alleles ; Case-Control Studies ; Female ; Gene frequency ; genotypes ; Genotyping ; Haplotypes ; Heterozygotes ; Homozygotes ; Humans ; insulin resistance ; Plasma levels ; Polycystic ovary syndrome ; Polycystic Ovary Syndrome - genetics ; Polymorphism, Single Nucleotide ; resistin ; Resistin - genetics ; Single-nucleotide polymorphism</subject><ispartof>American journal of reproductive immunology (1989), 2023-07, Vol.90 (1), p.e13731-n/a</ispartof><rights>2023 John Wiley &amp; Sons A/S. 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As its expression is partly inherited, a role for RETN polymorphisms in regulating resistin levels and PCOS risk was shown, but with varied results. Aim To investigate the association of rs34124816 (–537A&gt;C), rs1862513 (–420C&gt;G), rs3219175 (–358G&gt;A), rs3745367 (+299G&gt;A), rs3745369 (+1263G&gt;C), and rs1423096 (+4965C&gt;T) RETN SNPs with PCOS. Methods Study subjects included 583 women with PCOS, and 713 eumenorrheic women serving as controls. Genotyping was done by real‐time PCR. Results Higher minor allele frequency (MAF) of rs34124816, rs3219175, and rs3745369, and lower MAF of rs1862513 and rs1423096 were seen in PCOS cases. Reduced PCOS risk was found with rs3745367 minor‐allele homozygotes and rs1423096 minor‐allele homozygotes, while increased risk was linked with rs3745367 heterozygotes, and with rs3745369 heterozygotes and minor‐allele homozygotes. While it did not reach statistical significance, serum resistin levels were elevated in PCOS cases than in control women and major‐allele homozygotes of rs34124816 and rs1862513, and in rs1423096 minor‐allele‐containing carriers. Carriage of rs34124816 correlated positively with age and LH, whereas rs1862513 positively and rs3745367 negatively correlated with fasting glucose. Six‐locus (rs34124816‐rs1862513‐rs3219175‐rs3745367‐rs3745369‐rs1423096) haplotype analysis demonstrated a significant reduction in AGGGGG and a marked increase in AGGGCG haplotypes between cases and controls, thus assigning PCOS protective and susceptible nature to these haplotypes, respectively. Conclusions This study is the first to document the contribution of rs34124816 and rs1423096 RETN variants to the risk of PCOS. 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Saldhana, Fabiola Lisa ; Bauyrzhanova, Zhansaya ; Nemr, Rita ; Mahmood, Naeema A. ; Almawi, Wassim Y.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3531-18081907778ff289b048a0ddbdc9b13113bd9571566f0a917c4d2e4efe586453</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Alleles</topic><topic>Case-Control Studies</topic><topic>Female</topic><topic>Gene frequency</topic><topic>genotypes</topic><topic>Genotyping</topic><topic>Haplotypes</topic><topic>Heterozygotes</topic><topic>Homozygotes</topic><topic>Humans</topic><topic>insulin resistance</topic><topic>Plasma levels</topic><topic>Polycystic ovary syndrome</topic><topic>Polycystic Ovary Syndrome - genetics</topic><topic>Polymorphism, Single Nucleotide</topic><topic>resistin</topic><topic>Resistin - genetics</topic><topic>Single-nucleotide polymorphism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Al‐Awadi, Aminah M.</creatorcontrib><creatorcontrib>Saldhana, Fabiola Lisa</creatorcontrib><creatorcontrib>Bauyrzhanova, Zhansaya</creatorcontrib><creatorcontrib>Nemr, Rita</creatorcontrib><creatorcontrib>Mahmood, Naeema A.</creatorcontrib><creatorcontrib>Almawi, Wassim Y.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>American journal of reproductive immunology (1989)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Al‐Awadi, Aminah M.</au><au>Saldhana, Fabiola Lisa</au><au>Bauyrzhanova, Zhansaya</au><au>Nemr, Rita</au><au>Mahmood, Naeema A.</au><au>Almawi, Wassim Y.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Relation of resistin gene variants to resistin plasma levels and altered susceptibility to polycystic ovary syndrome: A case control study</atitle><jtitle>American journal of reproductive immunology (1989)</jtitle><addtitle>Am J Reprod Immunol</addtitle><date>2023-07</date><risdate>2023</risdate><volume>90</volume><issue>1</issue><spage>e13731</spage><epage>n/a</epage><pages>e13731-n/a</pages><issn>1046-7408</issn><eissn>1600-0897</eissn><abstract>Background A role for resistin in the pathogenesis of polycystic ovarian syndrome (PCOS) and related features were described for various ethnicities. As its expression is partly inherited, a role for RETN polymorphisms in regulating resistin levels and PCOS risk was shown, but with varied results. Aim To investigate the association of rs34124816 (–537A&gt;C), rs1862513 (–420C&gt;G), rs3219175 (–358G&gt;A), rs3745367 (+299G&gt;A), rs3745369 (+1263G&gt;C), and rs1423096 (+4965C&gt;T) RETN SNPs with PCOS. Methods Study subjects included 583 women with PCOS, and 713 eumenorrheic women serving as controls. Genotyping was done by real‐time PCR. Results Higher minor allele frequency (MAF) of rs34124816, rs3219175, and rs3745369, and lower MAF of rs1862513 and rs1423096 were seen in PCOS cases. Reduced PCOS risk was found with rs3745367 minor‐allele homozygotes and rs1423096 minor‐allele homozygotes, while increased risk was linked with rs3745367 heterozygotes, and with rs3745369 heterozygotes and minor‐allele homozygotes. While it did not reach statistical significance, serum resistin levels were elevated in PCOS cases than in control women and major‐allele homozygotes of rs34124816 and rs1862513, and in rs1423096 minor‐allele‐containing carriers. Carriage of rs34124816 correlated positively with age and LH, whereas rs1862513 positively and rs3745367 negatively correlated with fasting glucose. Six‐locus (rs34124816‐rs1862513‐rs3219175‐rs3745367‐rs3745369‐rs1423096) haplotype analysis demonstrated a significant reduction in AGGGGG and a marked increase in AGGGCG haplotypes between cases and controls, thus assigning PCOS protective and susceptible nature to these haplotypes, respectively. Conclusions This study is the first to document the contribution of rs34124816 and rs1423096 RETN variants to the risk of PCOS. The varied association of RETN gene variants with PCOS suggests an ethnic contribution of RETN association with PCOS.</abstract><cop>Denmark</cop><pub>Wiley Subscription Services, Inc</pub><pmid>37382171</pmid><doi>10.1111/aji.13731</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0003-3772-0813</orcidid><orcidid>https://orcid.org/0000-0003-0932-7504</orcidid><orcidid>https://orcid.org/0000-0003-1633-9757</orcidid><orcidid>https://orcid.org/0000-0002-0859-198X</orcidid></addata></record>
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subjects Alleles
Case-Control Studies
Female
Gene frequency
genotypes
Genotyping
Haplotypes
Heterozygotes
Homozygotes
Humans
insulin resistance
Plasma levels
Polycystic ovary syndrome
Polycystic Ovary Syndrome - genetics
Polymorphism, Single Nucleotide
resistin
Resistin - genetics
Single-nucleotide polymorphism
title Relation of resistin gene variants to resistin plasma levels and altered susceptibility to polycystic ovary syndrome: A case control study
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