Limits...
Fine mapping of the uterine leiomyoma locus on 1q43 close to a lncRNA in the RGS7-FH interval.

Aissani B, Zhang K, Mensenkamp AR, Menko FH, Wiener HW - Endocr. Relat. Cancer (2015)

Bottom Line: In race-combined analyses and in meta-analyses (n=916), we identified promising associations with risk peaking upstream of a non-protein coding RNA (lncRNA) locus located in the RGS7-FH interval closer to RGS7, and associations with tumor size peaking in the distal phospholipase D family, member 5 (PLD5) gene at rs2654879 (P=1.7×10(-4)).We corroborated previously reported FH mutations in nine out of the 18 HLRCC-associated UL cases and identified two missense mutations in FH in only two nonsyndromic UL cases and one control.While the identified variations at 1q43 represent a potential risk locus for UL, future replication analyses are required to substantiate our observation.

View Article: PubMed Central - PubMed

Affiliation: Department of EpidemiologyR217JDepartment of BiostatisticsSchool of Public Health, University of Alabama at Birmingham, 1665 University Boulevard, Birmingham, Alabama 35294-0022, USADepartment of Human GeneticsRadboud University Medical Center Nijmegen, Nijmegen, The NetherlandsNetherlands Cancer InstituteAmsterdam, The Netherlands baissani@uab.edu.

No MeSH data available.


Related in: MedlinePlus

Genomic annotation of the candidate uterine leiomyoma locus on human chromosome 1q43. The genomic map shows the location of the single nucleotide polymorphism (SNP) sites at which the association with risk of uterine leiomyoma (UL) peaked in the pooled analysis (rs2341938) and meta-analysis (rs78220092) between centromeric (cen) regulator of G-protein signaling 7 (RGS7) and telomeric (tel) fumarate hydratase (FH). The map shows also the relative location of lnc-RNA TCONS_l2_00000923 containing the SNP (rs1891129) associated with UL and with FH expression in peripheral blood mononuclear cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4526794&req=5

fig2: Genomic annotation of the candidate uterine leiomyoma locus on human chromosome 1q43. The genomic map shows the location of the single nucleotide polymorphism (SNP) sites at which the association with risk of uterine leiomyoma (UL) peaked in the pooled analysis (rs2341938) and meta-analysis (rs78220092) between centromeric (cen) regulator of G-protein signaling 7 (RGS7) and telomeric (tel) fumarate hydratase (FH). The map shows also the relative location of lnc-RNA TCONS_l2_00000923 containing the SNP (rs1891129) associated with UL and with FH expression in peripheral blood mononuclear cells.

Mentions: No reference gene sequence maps to this genomic interval in the human genome assembly 19 (GRCh37/hg19). However, expressed sequence annotations from different sources indicate the presence of a large intergenic non-coding RNA (lncRNA) gene located about 30 kb telomeric to the peak of association (Fig. 2). Several SNPs located in the lncRNA locus showed moderate associations (P≤0.01) with either risk or tumor size (Supplementary Table S1). In particular, a common SNP (rs1891129 C>T at position 241 586 687) in the lncRNA that showed moderate associations with risk (P=0.017) and tumor size (P=0.037 in case only-design and P=0.0027 in the four-level design) (Table 2) is an expression quantitative trait locus (eQTL) significantly associated (β coefficient=23.9, P=0.003) with FH but not with RGS7 (β=−2.26, P=0.31) expression (Supplementary Figures S4 and S5, see section on supplementary data given at the end of this article) in blood (Heinzen et al. 2008). No eQTL information was available in the SNPexpress database for the other candidate SNPs listed in Table 2 except for rs4660080, which showed no significant association with either RGS7 or FH, and for the distal SNPs rs2654879 and rs6429360, which were not associated with PLD5 expression.


Fine mapping of the uterine leiomyoma locus on 1q43 close to a lncRNA in the RGS7-FH interval.

Aissani B, Zhang K, Mensenkamp AR, Menko FH, Wiener HW - Endocr. Relat. Cancer (2015)

Genomic annotation of the candidate uterine leiomyoma locus on human chromosome 1q43. The genomic map shows the location of the single nucleotide polymorphism (SNP) sites at which the association with risk of uterine leiomyoma (UL) peaked in the pooled analysis (rs2341938) and meta-analysis (rs78220092) between centromeric (cen) regulator of G-protein signaling 7 (RGS7) and telomeric (tel) fumarate hydratase (FH). The map shows also the relative location of lnc-RNA TCONS_l2_00000923 containing the SNP (rs1891129) associated with UL and with FH expression in peripheral blood mononuclear cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4526794&req=5

fig2: Genomic annotation of the candidate uterine leiomyoma locus on human chromosome 1q43. The genomic map shows the location of the single nucleotide polymorphism (SNP) sites at which the association with risk of uterine leiomyoma (UL) peaked in the pooled analysis (rs2341938) and meta-analysis (rs78220092) between centromeric (cen) regulator of G-protein signaling 7 (RGS7) and telomeric (tel) fumarate hydratase (FH). The map shows also the relative location of lnc-RNA TCONS_l2_00000923 containing the SNP (rs1891129) associated with UL and with FH expression in peripheral blood mononuclear cells.
Mentions: No reference gene sequence maps to this genomic interval in the human genome assembly 19 (GRCh37/hg19). However, expressed sequence annotations from different sources indicate the presence of a large intergenic non-coding RNA (lncRNA) gene located about 30 kb telomeric to the peak of association (Fig. 2). Several SNPs located in the lncRNA locus showed moderate associations (P≤0.01) with either risk or tumor size (Supplementary Table S1). In particular, a common SNP (rs1891129 C>T at position 241 586 687) in the lncRNA that showed moderate associations with risk (P=0.017) and tumor size (P=0.037 in case only-design and P=0.0027 in the four-level design) (Table 2) is an expression quantitative trait locus (eQTL) significantly associated (β coefficient=23.9, P=0.003) with FH but not with RGS7 (β=−2.26, P=0.31) expression (Supplementary Figures S4 and S5, see section on supplementary data given at the end of this article) in blood (Heinzen et al. 2008). No eQTL information was available in the SNPexpress database for the other candidate SNPs listed in Table 2 except for rs4660080, which showed no significant association with either RGS7 or FH, and for the distal SNPs rs2654879 and rs6429360, which were not associated with PLD5 expression.

Bottom Line: In race-combined analyses and in meta-analyses (n=916), we identified promising associations with risk peaking upstream of a non-protein coding RNA (lncRNA) locus located in the RGS7-FH interval closer to RGS7, and associations with tumor size peaking in the distal phospholipase D family, member 5 (PLD5) gene at rs2654879 (P=1.7×10(-4)).We corroborated previously reported FH mutations in nine out of the 18 HLRCC-associated UL cases and identified two missense mutations in FH in only two nonsyndromic UL cases and one control.While the identified variations at 1q43 represent a potential risk locus for UL, future replication analyses are required to substantiate our observation.

View Article: PubMed Central - PubMed

Affiliation: Department of EpidemiologyR217JDepartment of BiostatisticsSchool of Public Health, University of Alabama at Birmingham, 1665 University Boulevard, Birmingham, Alabama 35294-0022, USADepartment of Human GeneticsRadboud University Medical Center Nijmegen, Nijmegen, The NetherlandsNetherlands Cancer InstituteAmsterdam, The Netherlands baissani@uab.edu.

No MeSH data available.


Related in: MedlinePlus