Browsing by Author "Kamboh, M. Ilyas"
Now showing 1 - 3 of 3
- Results Per Page
- Sort Options
Publication Apolipoprotein E-C1-C4-C2 gene cluster region and inter-individual variation in plasma lipoprotein levels: A comprehensive genetic association study in two ethnic groups(Public Library Science, 2019-03-26) Pirim, Dilek; Radwan, Zaheda H.; Wang, Xingbin; Niemsiri, Vipavee; Hokanson, John E.; Hamman, Richard F.; Feingold, Eleanor; Bunker, Clareann H.; Demirci, F. Yesim; Kamboh, M. Ilyas; PİRİM, DİLEK; Bursa Uludağ Üniversitesi/Edebiyat Fakültesi/Moleküler Biyoloji ve Genetik Bölümü; 0000-0002-0522-9432; ABA-4957-2020; HTP-6233-2023The apolipoprotein E-C1-C4-C2 gene cluster at 19q13.32 encodes four amphipathic apolipo proteins. The influence of APOE common polymorphisms on plasma lipid/lipoprotein profile, especially on LDL-related traits, is well recognized; however, little is known about the role of other genes/variants in this gene cluster. In this study, we evaluated the role of common and uncommon/rare genetic variation in this gene region on inter-individual variation in plasma lipoprotein levels in non-Hispanic Whites (NHWs) and African blacks (ABs). In the variant discovery step, the APOE, APOC1, APOC4, APOC2 genes were sequenced along with their flanking and hepatic control regions (HCR1 and HCR2) in 190 subjects with extreme HDL-C/TG levels. The next step involved the genotyping of 623 NHWs and 788 ABs for the identified uncommon/rare variants and common tagSNPs along with additional relevant SNPs selected from public resources, followed by association analyses with lipid traits. A total of 230 sequence variants, including 15 indels were identified, of which 65 were novel. A total of 70 QC-passed variants in NHWs and 108 QC-passed variants in ABs were included in the final association analyses. Single-site association analysis of SNPs with MAF>1% revealed 20 variants in NHWs and 24 variants in ABs showing evidence of association with at least one lipid trait, including several variants exhibiting independent associations from the established APOE polymorphism even after multiple-testing correction. Overall, our study has confirmed known associations and also identified novel associations in this genomic region with various lipid traits. Our data also support the contribution of both common and uncommon/rare variation in this gene region in affecting plasma lipid profile in the general population.Publication Association study of coronary artery disease-associated genome-wide significant SNPS with coronary stenosis in Pakistani population(Hindawi, 2020-01-23) Cheema, Asma Naseer; Pirim, Dilek; Wang, Xingbin; Ali, Jabar; Bhatti, Attya; John, Peter; Feingold, Eleanor; Demirci, F. Yeşim; Kamboh, M. Ilyas; PİRİM, DİLEK; Bursa Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Moleküler Biyoloji ve Genetik Bölümü.; 0000-0002-0522-9432; ABA-4957-2020Genome-wide association studies (GWAS) of coronary artery disease (CAD) have revealed multiple genetic risk loci. We assessed the association of 47 genome-wide significant single-nucleotide polymorphisms (SNPs) at 43 CAD loci with coronary stenosis in a Pakistani sample comprising 663 clinically ascertained and angiographically confirmed cases. Genotypes were determined using the iPLEX Gold technology. All statistical analyses were performed using R software. Linkage disequilibrium (LD) between significant SNPs was determined using SNAP web portal, and functional annotation of SNPs was performed using the RegulomeDB and Genotype-Tissue Expression (GTEx) databases. Genotyping comparison was made between cases with severe stenosis (>= 70%) and mild/minimal stenosis (<30%). Five SNPs demonstrated significant associations: three with additive genetic modelsPLG/rs4252120 (p=0.0078),KIAA1462/rs2505083 (p=0.005), andSLC22A3/rs2048327 (p=0.045) and two with recessive modelsSORT1/rs602633 (p=0.005) andUBE2Z/rs46522 (p=0.03).PLG/rs4252120 was in LD with two functionalPLGvariants (rs4252126 and rs4252135), each with a RegulomeDB score of 1f. Likewise,KIAA1462/rs2505083 was in LD with a functional SNP,KIAA1462/rs3739998, having a RegulomeDB score of 2b. In the GTEx database,KIAA1462/rs2505083,SLC22A3/rs2048327,SORT1/rs602633, andUBE2Z/rs46522 SNPs were found to be expression quantitative trait loci (eQTLs) in CAD-associated tissues. In conclusion, five genome-wide significant SNPs previously reported in European GWAS were replicated in the Pakistani sample. Further association studies on larger non-European populations are needed to understand the worldwide genetic architecture of CAD.Publication Hepatic lipase (LIPC) sequencing in individuals with extremely high and low high-density lipoprotein cholesterol levels(Public Library Science, 2020-12-16) Bunker, Clareann H.; Hokanson, John E.; Hamman, Richard F.; Demirci, F. Yesim; Kamboh, M. Ilyas; Pirim, Dilek; PİRİM, DİLEK; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Moleküler Biyoloji ve Genetik.; 0000-0002-0522-9432; ABA-4957-2020; HTP-6233-2023Common variants in the hepatic lipase (LIPC) gene have been shown to be associated with plasma lipid levels; however, the distribution and functional features of rare and regulatory LIPC variants contributing to the extreme lipid phenotypes are not well known. This study was aimed to catalogue LIPC variants by resequencing the entire LIPC gene in 95 non-Hispanic Whites (NHWs) and 95 African blacks (ABs) with extreme HDL-C levels followed by in silico functional analyses. A total of 412 variants, including 43 novel variants were identified; 56 were unique to NHWs and 234 were unique to ABs. Seventy-eight variants in NHWs and 89 variants in ABs were present either in high HDL-C group or low HDL-C group. Two non-synonymous variants (p.S289F, p.T405M), found in NHWs with high HDL-C group were predicted to have damaging effect on LIPC protein by SIFT, MT2 and PP2. We also found several non-coding variants that possibly reside in the circRNA and lncRNA binding sites and may have regulatory potential, as identified in rSNPbase and RegulomeDB databases. Our results shed light on the regulatory nature of rare and non-coding LIPC variants as well as suggest their important contributions in affecting the extreme HDL-C phenotypes.