Polymorphisms in PDLIM5 gene are associated with alcohol dependence, type 2 diabetes, and hypertension.
The PDZ and LIM domain 5 (PDLIM5) gene may play a role in alcohol dependence (AD), bipolar disorder, and major depressive disorder; however, no study has identified shared genetic variants within PDLIM5 gene among AD, type 2 diabetes (T2D), and hypertension. This study investigated the association of 72 single nucleotide polymorphism (SNPs) with AD (1066 AD cases and 1278 controls) in the Study of Addiction - Genetics and Environment (SAGE) sample and 47 SNPs with T2D (878 cases and 2686 non-diabetic) and hypertension (825 cases and 2739 non-hypertensive) in the Marshfield sample. Multiple logistic regression models in PLINK software were used to examine the associations of genetic variants with AD, T2D, and hypertension and SNP x alcohol consumption interactions for T2D and hypertension. Twenty-five SNPs were associated with AD in the SAGE sample (p < 0.05); rs1048627 showed the strongest association with AD (p = 5.53 × 10-4). Of the 25 SNPs, 5 SNPs showed associations with both AD in the SAGE sample and T2D in the Marshfield sample (top SNP rs11097432 with p = 0.00107 for T2D and p = 0.0483 for AD) while 6 SNPs showed associations with both AD in the SAGE sample and hypertension in the Marshfield sample (top SNP rs12500426 with p = 0.0119 for hypertension and p = 1.51 × 10-3for AD). SNP (rs6532496) showed significant interaction with alcohol consumption for hypertension. Our results showed that several genetic variants in PDLIM5 gene influence AD, T2D and hypertension. These findings offer the potential for new insights into the pathogenesis of AD, T2D, and hypertension.
Department of Biostatistics and Epidemiology, College of Public Health, East Tennessee State University, Johnson City, TN 37614, USA.
Daniel
D
Owusu
Department of Public Health Sciences, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
Yue
Y
Pan
Division of Biostatistics and Bioinformatics, Department of Environmental Health, University of Cincinnati, Cincinnati, OH 45267, USA.
Changchun
C
Xie
Department of Pharmaceutical Sciences, Gatton College of Pharmacy, East Tennessee State University, Johnson City, TN 37614, USA.
Sam
S
Harirforoosh
Department of Biostatistics and Epidemiology, College of Public Health, East Tennessee State University, Johnson City, TN 37614, USA. Electronic address: wangk@etsu.edu.
Ke-Sheng
KS
Wang
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000437:Alcoholism / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006239:Haplotypes; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D060588:LIM Domain Proteins / Q000235:genetics*; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
D048868:Adaptor Proteins, Signal Transducing; D060588:LIM Domain Proteins; C512485:PDLIM5 protein, human
Alcohol dependence; Hypertension; Interaction; PDLIM5; Pleotropic effect; Single nucleotide polymorphism; Type 2 diabetes