BACKGROUND: The genetic basis of major depressive disorder (MDD) has been explored extensively, but the mode of transmission of the disease has yet to be established. To better understand the mechanism by which the monoamine oxidase A (MAOA) gene may play a role in developing MDD, the present work examined the cis-phase interaction between genetic variants within the MAOA gene for the pathogenesis of MDD. METHODS: A variable number tandem repeat (VNTR) and 19 single nucleotide polymorphisms (SNPs) within the gene were genotyped in 512 unrelated patients with MDD and 567 unrelated control subjects among a Chinese population. Quantitative real-time polymerase chain reaction analysis was applied to test the effect of genetic variants on expression of the MAOA gene in MDD. RESULTS: Neither the VNTR polymorphism nor seven informative SNPs showed allelic association with MDD, but the cis-acting interactions between the VNTR polymorphism and four individual SNPs were strongly associated with MDD risk, of which the VNTR-rs1465107 combination showed the strongest association (p = .000011). Quantitative real-time polymerase chain reaction analysis showed that overall relative quantity of MAOA messenger RNA was significantly higher in patients with MDD than in control subjects (fold change = 5.28, p = 1.7 × 10⁻⁷) and that in the male subjects carrying the VNTR-L, rs1465107-A, rs6323-G, rs2072743-A, or rs1137070-T alleles, expression of MAOA messenger RNA was significantly higher in the patient group than in the control group. CONCLUSIONS: The cis-phase interaction between the VNTR polymorphism and functional SNPs may contribute to the etiology of MDD.
BACKGROUND: The genetic basis of major depressive disorder (MDD) has been explored extensively, but the mode of transmission of the disease has yet to be established. To better understand the mechanism by which the monoamine oxidase A (MAOA) gene may play a role in developing MDD, the present work examined the cis-phase interaction between genetic variants within the MAOA gene for the pathogenesis of MDD. METHODS: A variable number tandem repeat (VNTR) and 19 single nucleotide polymorphisms (SNPs) within the gene were genotyped in 512 unrelated patients with MDD and 567 unrelated control subjects among a Chinese population. Quantitative real-time polymerase chain reaction analysis was applied to test the effect of genetic variants on expression of the MAOA gene in MDD. RESULTS: Neither the VNTR polymorphism nor seven informative SNPs showed allelic association with MDD, but the cis-acting interactions between the VNTR polymorphism and four individual SNPs were strongly associated with MDD risk, of which the VNTR-rs1465107 combination showed the strongest association (p = .000011). Quantitative real-time polymerase chain reaction analysis showed that overall relative quantity of MAOA messenger RNA was significantly higher in patients with MDD than in control subjects (fold change = 5.28, p = 1.7 × 10⁻⁷) and that in the male subjects carrying the VNTR-L, rs1465107-A, rs6323-G, rs2072743-A, or rs1137070-T alleles, expression of MAOA messenger RNA was significantly higher in the patient group than in the control group. CONCLUSIONS: The cis-phase interaction between the VNTR polymorphism and functional SNPs may contribute to the etiology of MDD.
Authors: Ming Li; Andrew E Jaffe; Richard E Straub; Ran Tao; Joo Heon Shin; Yanhong Wang; Qiang Chen; Chao Li; Yankai Jia; Kazutaka Ohi; Brady J Maher; Nicholas J Brandon; Alan Cross; Joshua G Chenoweth; Daniel J Hoeppner; Huijun Wei; Thomas M Hyde; Ronald McKay; Joel E Kleinman; Daniel R Weinberger Journal: Nat Med Date: 2016-05-09 Impact factor: 53.440
Authors: Karin Hek; Ayse Demirkan; Jari Lahti; Antonio Terracciano; Alexander Teumer; Cornelia M van Duijn; Hans J Grabe; Lenore J Launer; Kathryn L Lunetta; Thomas H Mosley; Anne B Newman; Henning Tiemeier; Joanne Murabito; Marilyn C Cornelis; Najaf Amin; Erin Bakshis; Jens Baumert; Jingzhong Ding; Yongmei Liu; Kristin Marciante; Osorio Meirelles; Michael A Nalls; Yan V Sun; Nicole Vogelzangs; Lei Yu; Stefania Bandinelli; Emelia J Benjamin; David A Bennett; Dorret Boomsma; Alessandra Cannas; Laura H Coker; Eco de Geus; Philip L De Jager; Ana V Diez-Roux; Shaun Purcell; Frank B Hu; Eric B Rimma; David J Hunter; Majken K Jensen; Gary Curhan; Kenneth Rice; Alan D Penman; Jerome I Rotter; Nona Sotoodehnia; Rebecca Emeny; Johan G Eriksson; Denis A Evans; Luigi Ferrucci; Myriam Fornage; Vilmundur Gudnason; Albert Hofman; Thomas Illig; Sharon Kardia; Margaret Kelly-Hayes; Karestan Koenen; Peter Kraft; Maris Kuningas; Joseph M Massaro; David Melzer; Antonella Mulas; Cornelis L Mulder; Anna Murray; Ben A Oostra; Aarno Palotie; Brenda Penninx; Astrid Petersmann; Luke C Pilling; Bruce Psaty; Rajesh Rawal; Eric M Reiman; Andrea Schulz; Joshua M Shulman; Andrew B Singleton; Albert V Smith; Angelina R Sutin; André G Uitterlinden; Henry Völzke; Elisabeth Widen; Kristine Yaffe; Alan B Zonderman; Francesco Cucca; Tamara Harris; Karl-Heinz Ladwig; David J Llewellyn; Katri Räikkönen; Toshiko Tanaka Journal: Biol Psychiatry Date: 2013-01-03 Impact factor: 13.382
Authors: Daniel F Kripke; Caroline M Nievergelt; Greg J Tranah; Sarah S Murray; Michael J McCarthy; Katharine M Rex; Neeta Parimi; John R Kelsoe Journal: J Circadian Rhythms Date: 2011-08-09
Authors: Su Kang Kim; Hae Jeong Park; Hosik Seok; Hye Sook Jeon; Joo-Ho Chung; Won Sub Kang; Jong Woo Kim; Gyeong Im Yu; Dong Hoon Shin Journal: Mol Biol Rep Date: 2014-02-09 Impact factor: 2.316