Association of multiple nucleotide variations in the pituitary glutaminyl cyclase gene QPC with low radial BMD in adult women.

2020 ◽  
Author(s):  
Lungwani Muungo
Keyword(s):  
Linkage Disequilibrium ◽  
Multiple Regression ◽  
Genetic Variations ◽  
Strong Linkage Disequilibrium ◽  
Adult Women ◽  
Nucleotide Polymorphisms ◽  
Haplotype Estimation ◽  
Factors Affecting ◽  
Glutaminyl Cyclase ◽  
Strong Linkage

Correlation between 13 genetic variations of the glutaminyl-peptide cyclotransferase gene andadjusted aBMD was tested among 384 adult women. Among 13 variations with strong linkage disequilibrium,R54W showed a prominent association (p ? 0.0003), which was more striking when examined among 309 eldersubjects (>50 years; p ? 0.0001). Contribution for postmenopausal bone loss was suggested.Introduction: Alterations in homeostatic regulation of estrogen through the hypothalamus-pituitary-gonadal axis(HPG axis) importantly affect the pathogenesis of osteoporosis. Osteoporosis-susceptibility genes have beenproposed in this hormonal axis, such as estrogen receptor genes and the gonadotropin-releasing hormone gene(GnRH). Here we report another example of genes: glutaminyl-peptide cyclotransferase gene (QPCT), an essentialmodifier of pituitary peptide hormones, including GnRH.Materials and Methods: Analyses of association of 13 single nucleotide polymorphisms (SNPs) at the QPCT locuswith adjusted areal BMD (adj-aBMD) were carried out among 384 adult women. Linkage disequilibrium (LD) wasanalyzed by haplotype estimation and calculation of D? and r2. Multiple regression analysis was applied forevaluating the combined effects of the variations.Results and Conclusions: LD analysis indicated strong linkage disequilibrium within the entire 30-kb region of theQPCT gene. Significant correlations were observed between the genotypes of the six SNPs and the radial adj-aBMD,among which R54W (nt ? 160C?T) presented the most prominent association (p ? 0.0003). Striking associationwas observed for these SNPs among the 309 subjects ?50 years of age (R54W, p ? 0.0001; ?1095T?C, p ?0.0002; ?1844C?T, p ? 0.0002). Multiple regression analyses indicated that multiple SNPs in the gene might actin combination to determine the radial adj-aBMD. These results indicate that genetic variations in QPCT are theimportant factors affecting the BMD of adult women that contribute to susceptibility for osteoporosis. The datashould provide new insight into the etiology of the disease and may suggest a new target to be considered duringtreatment.J Bone Miner

scholarly journals Polymorphisms in the Sortilin-Related Receptor 1 Gene Are Associated with Cognitive Impairment in Filipinos

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Cristine R. Casingal ◽  
Maria Luisa G. Daroy ◽  
Cynthia A. Mapua ◽  
Dianne Jane A. Florendo ◽  
Filipinas F. Natividad ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Linkage Disequilibrium ◽  
Amyloid Plaques ◽  
Transport Processes ◽  
Strong Linkage Disequilibrium ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Strong Linkage ◽  
Neuronal Transport

Background/Aims. Sortilin-related receptor 1 (SORL1) is involved in the neuronal transport processes and plays a role in the formation of amyloid plaques. This study investigated the association of 6 SORL1 single nucleotide polymorphisms (SNPs 8, 9, 10, 13, 19, and 23) with cognitive impairment (CI) in Filipinos. Methods. DNA samples from 484 subjects (100 Alzheimer’s Disease (AD) cases, 109 mild cognitive impairment (MCI) cases, 18 other types of CI, and 257 no dementia controls (NDC)) were genotyped using TaqMan SNP Genotyping Assays. Data Analysis. Our study showed strong linkage disequilibrium in the SNPs 8, 9, and 10 block. Our results showed that CI was significantly associated with SNPs 13 and 23. None of the SORL1 SNPs studied was associated with AD while SNPs 8, 9, 10, and 23 were associated with MCI. Conclusion. The findings had provided evidence that SORL1 may predispose individuals to CI. Further studies are needed to clarify the role of SORL1 in Filipinos with AD.

Linkage and linkage disequilibrium analysis of the lipoprotein lipase gene with lipid profiles in Chinese hypertensive families

2005 ◽  
Vol 108 (2) ◽  
pp. 137-142 ◽  
Author(s):  
Wenjie YANG ◽  
Jianfeng HUANG ◽  
Cailiang YAO ◽  
Shaoyong SU ◽  
Donghai LIU ◽  
...  
Keyword(s):  
Linkage Disequilibrium ◽  
Lipoprotein Lipase ◽  
Lipid Profiles ◽  
Strong Linkage Disequilibrium ◽  
Nucleotide Polymorphisms ◽  
Linkage Disequilibrium Analysis ◽  
Lipid Levels ◽  
Lipase Gene ◽  
Significant Independent Risk Factor ◽  
Lpl Gene

Elevated TG [triacylglycerol (triglyceride)] is a significant independent risk factor for cardiovascular disease. LPL (lipoprotein lipase) is one of the key enzymes in the metabolism of the TG-rich lipoproteins which hydrolyses TG from the chylomicrons and very-LDL (low-density lipoprotein). To investigate the relationship between the LPL gene and lipid profiles, especially TG, in 148 hypertensive families, we have chosen seven flanking microsatellite markers and four internal markers of the LPL gene and conducted linkage analysis by SOLAR and S.A.G.E. (statistical analysis for genetic epidemiology)/SIBPAL 2 programs, and linkage disequilibrium analysis by QTDT (quantitative transmission/disequilibrium test) and GOLD (graphical overview of linkage disequilibrium). There were statistically significant differences in lipid levels between subjects without and with hypertension within families. A maximum LOD score of 1.3 with TG at the marker D8S261 was observed by SOLAR. Using S.A.G.E./SIBPAL 2, we identified a linkage with TG at the marker ‘ATTT’ located within intron 6 of the LPL gene (P=0.0095). Two SNPs (single nucleotide polymorphisms), HindIII and HinfI, were found in linkage disequilibrium with LDL-cholesterol levels (P=0.0178 and P=0.0088 respectively). A strong linkage disequilibrium was observed between the HindIII in intron 8 and HinfI in the exon 9 (P<0.00001, D′=0.895). Linkage disequilibrium was also found between the ‘ATTT’ polymorphism in intron 6 and two SNPs (P=0.0021 and D′=0.611 for HindIII; and P=0.00004, D′=0.459 for HinfI). The present study in the Chinese families with hypertension suggested that the LPL gene might influence lipid levels, especially TG metabolism. Replication studies both in Chinese and other populations are warranted to confirm these results.

Valine 11 and phenylalanine 13 have a greater impact on the T-cell response to citrullinated peptides than the 70–74 shared epitope of the DRB1 molecule in macaques

2019 ◽  
Vol 78 (7) ◽  
pp. 917-921 ◽  
Author(s):  
Samuel Bitoun ◽  
Pierre Roques ◽  
Bernard Maillere ◽  
Roger Le Grand ◽  
Xavier Mariette
Keyword(s):  
Rheumatoid Arthritis ◽  
Linkage Disequilibrium ◽  
T Cell ◽  
Cell Response ◽  
Shared Epitope ◽  
Interferon Γ ◽  
T Cell Response ◽  
Strong Linkage Disequilibrium ◽  
Strong Linkage

ObjectivesVarious rheumatoid arthritis (RA) HLA-DRB-1 risk haplotypes have been regrouped under the shared epitope (SE) in position 70–74. The presence of Valine in position 11 (Val11) and phenylalanine in position 13 (Phe13) are also associated with RA, but it is impossible to differentiate their role compared with the SE since they are in strong linkage disequilibrium (LD) in humans. Similar to humans, certain macaques express the SE (H6). We analysed the effect of various DRB1 haplotypes on T-cell response to citrullinated peptides (Cit-P) in macaques.MethodsSix H6 and six non-H6 macaques were immunized with four Cit-P. T-cell response was assessed using Interferon γ enzyme-linked immunospot.ResultsAnimals developed a specific anti-Cit-P T-cell response. Surprisingly, H6 animals had a significantly lower T-cell response than non-H6. In macaques, the 70–74 SE and the Val11 are on separate haplotypes. Presence of Val11 was strongly associated with the anti-Cit-P T-cell response, whatever the 70–74 sequence was. This response was amplified in case of presence of Phe13.ConclusionThe absence of LD between Val11 and SE in macaques allowed us to demonstrate that the most important HLA positions to induce a T-cell response against Cit-P were Val11 and Phe13 and not the 70–74 SE.

Strong linkage disequilibrium of HLA DPw11 with the HLA B44-DR7-DQw2 extended haplotype*

1992 ◽  
Vol 39 (1) ◽  
pp. 35-37 ◽  
Author(s):  
J. D. Bignon ◽  
M. L. Cheneau ◽  
P. Herry ◽  
F. Bonneville ◽  
A. Cesbron ◽  
...  
Keyword(s):  
Linkage Disequilibrium ◽  
Strong Linkage Disequilibrium ◽  
Extended Haplotype ◽  
Strong Linkage

scholarly journals Association ofPTPN22Haplotypes (−1123G>C/+1858C>T) with Rheumatoid Arthritis in Western Mexican Population

2017 ◽  
Vol 2017 ◽  
pp. 1-5 ◽  
Author(s):  
Yeniley Ruiz-Noa ◽  
Jorge Ramón Padilla-Gutiérrez ◽  
Jorge Hernández-Bello ◽  
Claudia Azucena Palafox-Sánchez ◽  
Yeminia Valle ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Linkage Disequilibrium ◽  
Immune Tolerance ◽  
Tyrosine Phosphatase ◽  
Mexican Population ◽  
Strong Linkage Disequilibrium ◽  
Strong Linkage ◽  
Western Mexico ◽  
Pcr Rflp ◽  
Polymorphic Variants

Rheumatoid arthritis (RA) is an autoimmune disease characterized by the presence of antibodies against cyclic citrullinated peptide (anti-CCP), a consequence of the breakdown of immune tolerance. The lymphoid tyrosine phosphatase (Lyp) protein has significant effects on maintenance of peripheral immune tolerance. Two polymorphic variants (−1123G>C and +1858C>T) atPTPN22gene that encodes this protein have been associated with autoimmune disorders and found in strong linkage disequilibrium in Caucasian population. We evaluated whetherPTPN22haplotypes (−1123G>C/+1858C>T) are associated with anti-CCP antibodies, as well as susceptibility to RA in a Western Mexican population. A total of 315 RA patients and 315 control subjects (CS) were included. The polymorphisms were genotyped by PCR-RFLP and the anti-CCP antibodies were determined by ELISA. ThePTPN22polymorphisms were in strong linkage disequilibrium (D′ = 1.00 in CS). The susceptibility haplotype CT was significantly more frequent in RA patients than in CS (OR 2.18, 95% CI 1.15–4.16,p=0.01). No association between haplotypes and anti-CCP antibodies levels was observed. In conclusion, this study confirmed that −1123G>C and +1858C>TPTPN22polymorphisms are in strong linkage disequilibrium and the CT haplotype is a susceptibility marker to RA in Western Mexico. However, thePTPN22haplotypes are not associated with anti-CCP antibodies.

Strong linkage disequilibrium at the nucleotide analogue transporter ABCC5 gene locus

2005 ◽  
Vol 15 (2) ◽  
pp. 91-104 ◽  
Author(s):  
Pai Chung Gwee ◽  
Kun Tang ◽  
Pui Hoon Sew ◽  
Edmund J.D. Lee ◽  
Samuel S. Chong ◽  
...  
Keyword(s):  
Linkage Disequilibrium ◽  
Gene Locus ◽  
Strong Linkage Disequilibrium ◽  
Strong Linkage ◽  
Nucleotide Analogue

Does strong linkage disequilibrium guarantee redundant association results?

2008 ◽  
Vol 32 (6) ◽  
pp. 546-552 ◽  
Author(s):  
Dahlia M. Nielsen ◽  
Sunil Suchindran ◽  
Christopher P. Smith
Keyword(s):  
Linkage Disequilibrium ◽  
Strong Linkage Disequilibrium ◽  
Strong Linkage
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