The SLC6A14 Gene Shows Evidence of Association with Obesity

Overview

Journal J Clin Invest

Specialty General Medicine

Date 2003 Dec 9

PMID 14660752

Citations 52

Authors

Elina Suviolahti

Laura J Oksanen

Miina Ohman

Rita M Cantor

Martin Ridderstrale

Tiinamaija Tuomi

Jaakko Kaprio

Aila Rissanen

Pertti Mustajoki

Pekka Jousilahti

Erkki Vartiainen

Kaisa Silander

Riika Kilpikari

Veikko Salomaa

Leif Groop

Kimmo Kontula

Leena Peltonen

Paivi Pajukanta

Affiliations

Soon will be listed here.

Abstract

In our previous genome-wide scan of Finnish nuclear families, obesity was linked to chromosome Xq24. Here we analyzed this 15-Mb region by genotyping 9 microsatellite markers and 36 single nucleotide polymorphisms (SNPs) for 11 positional and functional candidate genes in an extended sample of 218 obese Finnish sibling pairs (sibpairs) (BMI > 30 kg/m2). Evidence of linkage emerged mainly from the obese male sibpairs, suggesting a gender-specific effect for the underlying gene. By constructing haplotypes among the obese male sibpairs, we restricted the region from 15 Mb to 4 Mb, between markers DXS8088 and DXS8067. Regional functional candidate genes were tested for association in an initial sample of 117 cases and 182 controls. Significant evidence was observed for association for an SNP in the 3'-untranslated region of the solute carrier family 6 member 14 (SLC6A14) gene (P = 0.0002) and for SNP haplotypes of the SLC6A14 gene (P = 0.0007-0.006). Furthermore, an independent replication study sample of 837 cases and 968 controls from Finland and Sweden also showed significant differences in allele frequencies between obese and non-obese individuals (P = 0.003). The SLC6A14 gene is an interesting novel candidate for obesity because it encodes an amino acid transporter, which potentially regulates tryptophan availability for serotonin synthesis and thus possibly affects appetite control.

Citing Articles

Immunogenetic Aspects of Sarcopenic Obesity.

Mazurkiewicz L, Czernikiewicz K, Grygiel-Gorniak B Genes (Basel). 2024; 15(2).

PMID: 38397196 PMC: 10888391. DOI: 10.3390/genes15020206.

Precision formulation, a new concept to improve dietary amino acid absorption based on the study of cationic amino acid transporters.

Morin G, Pinel K, Heraud C, Le-Garrec S, Wayman C, Dias K iScience. 2024; 27(2):108894.

PMID: 38318367 PMC: 10839688. DOI: 10.1016/j.isci.2024.108894.

Multi-tissue transcriptome analysis to identify candidate genes associated with weight regulation in Hanwoo cattle.

Jang S, Jang S, Kim J, Park W Front Genet. 2024; 14:1304638.

PMID: 38264212 PMC: 10803631. DOI: 10.3389/fgene.2023.1304638.

Flux coupling, not specificity, shapes the transport and phylogeny of SLC6 glycine transporters.

Le Guellec B, Rousseau F, Bied M, Supplisson S Proc Natl Acad Sci U S A. 2022; 119(41):e2205874119.

PMID: 36191186 PMC: 9564218. DOI: 10.1073/pnas.2205874119.

Factors Predisposing the Response to Lumacaftor/Ivacaftor in People with Cystic Fibrosis.

Mesinele J, Ruffin M, Guillot L, Boelle P, Corvol H, The French Cf Modifier Gene Study Investigators J Pers Med. 2022; 12(2).

PMID: 35207740 PMC: 8876860. DOI: 10.3390/jpm12020252.

References

Lahti-Koski M, Vartiainen E, Mannisto S, Pietinen P . Age, education and occupation as determinants of trends in body mass index in Finland from 1982 to 1997. Int J Obes Relat Metab Disord. 2000; 24(12):1669-76. DOI: 10.1038/sj.ijo.0801437. View

Pajukanta P, Cargill M, Viitanen L, Nuotio I, Kareinen A, Perola M . Two loci on chromosomes 2 and X for premature coronary heart disease identified in early- and late-settlement populations of Finland. Am J Hum Genet. 2000; 67(6):1481-93. PMC: 1287925. DOI: 10.1086/316902. View

Wauters M, Van Gaal L . Gender differences in leptin levels and physiology: a role for leptin in human reproduction. J Gend Specif Med. 2001; 2(5):46-51. View

Lahti-Koski M, Jousilahti P, Pietinen P . Secular trends in body mass index by birth cohort in eastern Finland from 1972 to 1997. Int J Obes Relat Metab Disord. 2001; 25(5):727-34. DOI: 10.1038/sj.ijo.0801588. View

Hugot J, Chamaillard M, Zouali H, Lesage S, Cezard J, Belaiche J . Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease. Nature. 2001; 411(6837):599-603. DOI: 10.1038/35079107. View

Rioux J, Daly M, Silverberg M, Lindblad K, Steinhart H, Cohen Z . Genetic variation in the 5q31 cytokine gene cluster confers susceptibility to Crohn disease. Nat Genet. 2001; 29(2):223-8. DOI: 10.1038/ng1001-223. View

Blaak E . Gender differences in fat metabolism. Curr Opin Clin Nutr Metab Care. 2001; 4(6):499-502. DOI: 10.1097/00075197-200111000-00006. View

Lindgren C, Mahtani M, Widen E, McCarthy M, Daly M, Kirby A . Genomewide search for type 2 diabetes mellitus susceptibility loci in Finnish families: the Botnia study. Am J Hum Genet. 2002; 70(2):509-16. PMC: 384923. DOI: 10.1086/338629. View

Soro A, Pajukanta P, Lilja H, Ylitalo K, Hiekkalinna T, Perola M . Genome scans provide evidence for low-HDL-C loci on chromosomes 8q23, 16q24.1-24.2, and 20q13.11 in Finnish families. Am J Hum Genet. 2002; 70(5):1333-40. PMC: 447608. DOI: 10.1086/339988. View

10.

Deng H, Deng H, Liu Y, Liu Y, Xu F, Shen H . A genomewide linkage scan for quantitative-trait loci for obesity phenotypes. Am J Hum Genet. 2002; 70(5):1138-51. PMC: 447591. DOI: 10.1086/339934. View

11.

Stone S, Abkevich V, Hunt S, Gutin A, Russell D, Neff C . A major predisposition locus for severe obesity, at 4p15-p14. Am J Hum Genet. 2002; 70(6):1459-68. PMC: 379132. DOI: 10.1086/340670. View

12.

Price R, Li W, Kilker R . An X-chromosome scan reveals a locus for fat distribution in chromosome region Xp21-22. Diabetes. 2002; 51(6):1989-91. DOI: 10.2337/diabetes.51.6.1989. View

13.

Benton D . Carbohydrate ingestion, blood glucose and mood. Neurosci Biobehav Rev. 2002; 26(3):293-308. DOI: 10.1016/s0149-7634(02)00004-0. View

14.

Chagnon Y, Rankinen T, Snyder E, Weisnagel S, Perusse L, Bouchard C . The human obesity gene map: the 2002 update. Obes Res. 2003; 11(3):313-67. DOI: 10.1038/oby.2003.47. View

15.

Stunkard A, Harris J, Pedersen N, McClearn G . The body-mass index of twins who have been reared apart. N Engl J Med. 1990; 322(21):1483-7. DOI: 10.1056/NEJM199005243222102. View

16.

Moll P, Burns T, Lauer R . The genetic and environmental sources of body mass index variability: the Muscatine Ponderosity Family Study. Am J Hum Genet. 1991; 49(6):1243-55. PMC: 1686453. View

17.

Terwilliger J . A powerful likelihood method for the analysis of linkage disequilibrium between trait loci and one or more polymorphic marker loci. Am J Hum Genet. 1995; 56(3):777-87. PMC: 1801166. View

18.

Korkeila M, Kaprio J, Rissanen A, Koskenvuo M . Consistency and change of body mass index and weight. A study on 5967 adult Finnish twin pairs. Int J Obes Relat Metab Disord. 1995; 19(5):310-7. View

19.

Kruglyak L, Lander E . Complete multipoint sib-pair analysis of qualitative and quantitative traits. Am J Hum Genet. 1995; 57(2):439-54. PMC: 1801561. View

20.

Harris J, Tambs K, Magnus P . Sex-specific effects for body mass index in the new Norwegian twin panel. Genet Epidemiol. 1995; 12(3):251-65. DOI: 10.1002/gepi.1370120303. View