Polymorphisms in PDLIM5 gene are associated with alcohol dependence, type 2 diabetes, and hypertension. (January 2017)

• Record Type: Journal Article
• Authors: Owusu, Daniel; Pan, Yue; Xie, Changchun; Harirforoosh, Sam; Wang, Ke-Sheng
• Is Part Of: Journal of psychiatric research. Volume 84(2017)
• Page Start: 27
• Page End: 34
• Publication Date: 2017-01
• Subjects: Alcohol dependence -- Type 2 diabetes -- Hypertension -- PDLIM5 -- Single nucleotide polymorphism -- Interaction -- Pleotropic effect; Psychiatry -- Periodicals; Mental Disorders -- Periodicals; Maladies mentales -- Périodiques; Psychiatry; Electronic journals; Periodicals; 616.89005
• DOI: 10.1016/j.jpsychires.2016.09.015
• Languages: English
• ISSNs: 0022-3956

Abstract

Abstract: 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 −3 for 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. Highlights: 25 SNPs in PDLIM5 associated with alcohol dependence. Of the 25 SNPs, 5 and 6 SNPs associated with type 2 diabetes and hypertension, respectively. The most significant SNP associated with alcohol dependence was rs1048627 with p = 5.53 × 10 −4 . The most significant SNP associated with type 2 diabetes was rs11097432 with p = 1.07 × 10 −3 . Pleotropic effect of PDLIM5 gene on alcohol dependence, type 2 diabetes and hypertension.