INTRODUCTION: Leptin (LEP) gene is one of the most promising candidate genes for obesity. Previous studies have tested the association of polymorphisms in LEP gene with obesity and obesity-related metabolic biomarkers (anthropometric variables, glucose, insulin level, leptin level and lipid profile). However, the results of these studies were still controversial. To determine whether LEP gene is associated with obesity in Tunisian population, we performed a family-based association study between LEP polymorphisms and obesity and obesity-related metabolic biomarkers. METHODS: Seven single nucleotide polymorphisms (SNPs) in 5' region of LEP gene were genotyped in three consanguineous families including 33 individuals. The previously reported LEP SNPs (H1328084, H1328082, rs10487506, H1328081, H1328080, G-2548A and A19G) were evaluated by PCR-RFLP and direct sequencing methods. Single SNP association and haplotype association analyses were performed using the family-based association test (FBAT). To determine allele frequencies of these SNPs in general population, 52 unrelated individuals from the general Tunisian population were also analyzed. RESULTS: Two SNPs showed significant associations with plasma leptin level (H1328084: A>G, Z=2.058, p=0.039; A19G: G>A, Z=2.058, p=0.039). When haplotypes were constructed with these two-markers, the risk AA haplotype (frequency 57.1%) was positively associated with plasma leptin level (Z=2.058, p=0.039). Moreover, SNPs H1328084 and A19G are predicted to modify transcription-factor binding sites. CONCLUSIONS: Our study provided that two functional variants in 5' regulatory region of LEP gene are associated with plasma leptin level as a quantitative trait. It suggested that H1328084 and A19G have an important role in regulating plasma leptin level.
INTRODUCTION:Leptin (LEP) gene is one of the most promising candidate genes for obesity. Previous studies have tested the association of polymorphisms in LEP gene with obesity and obesity-related metabolic biomarkers (anthropometric variables, glucose, insulin level, leptin level and lipid profile). However, the results of these studies were still controversial. To determine whether LEP gene is associated with obesity in Tunisian population, we performed a family-based association study between LEP polymorphisms and obesity and obesity-related metabolic biomarkers. METHODS: Seven single nucleotide polymorphisms (SNPs) in 5' region of LEP gene were genotyped in three consanguineous families including 33 individuals. The previously reported LEP SNPs (H1328084, H1328082, rs10487506, H1328081, H1328080, G-2548A and A19G) were evaluated by PCR-RFLP and direct sequencing methods. Single SNP association and haplotype association analyses were performed using the family-based association test (FBAT). To determine allele frequencies of these SNPs in general population, 52 unrelated individuals from the general Tunisian population were also analyzed. RESULTS: Two SNPs showed significant associations with plasma leptin level (H1328084: A>G, Z=2.058, p=0.039; A19G: G>A, Z=2.058, p=0.039). When haplotypes were constructed with these two-markers, the risk AA haplotype (frequency 57.1%) was positively associated with plasma leptin level (Z=2.058, p=0.039). Moreover, SNPs H1328084 and A19G are predicted to modify transcription-factor binding sites. CONCLUSIONS: Our study provided that two functional variants in 5' regulatory region of LEP gene are associated with plasma leptin level as a quantitative trait. It suggested that H1328084 and A19G have an important role in regulating plasma leptin level.
Authors: Shruti Dasgupta; Mohammed Salman; Lokesh B Siddalingaiah; G L Lakshmi; D Xaviour; Jwalapuram Sreenath Journal: Adipocyte Date: 2014-12-20 Impact factor: 4.534
Authors: Tuomas O Kilpeläinen; Jayne F Martin Carli; Alicja A Skowronski; Qi Sun; Jennifer Kriebel; Mary F Feitosa; Åsa K Hedman; Alexander W Drong; James E Hayes; Jinghua Zhao; Tune H Pers; Ursula Schick; Niels Grarup; Zoltán Kutalik; Stella Trompet; Massimo Mangino; Kati Kristiansson; Marian Beekman; Leo-Pekka Lyytikäinen; Joel Eriksson; Peter Henneman; Jari Lahti; Toshiko Tanaka; Jian'an Luan; Fabiola Del Greco M; Dorota Pasko; Frida Renström; Sara M Willems; Anubha Mahajan; Lynda M Rose; Xiuqing Guo; Yongmei Liu; Marcus E Kleber; Louis Pérusse; Tom Gaunt; Tarunveer S Ahluwalia; Yun Ju Sung; Yolande F Ramos; Najaf Amin; Antoinette Amuzu; Inês Barroso; Claire Bellis; John Blangero; Brendan M Buckley; Stefan Böhringer; Yii-Der I Chen; Anton J N de Craen; David R Crosslin; Caroline E Dale; Zari Dastani; Felix R Day; Joris Deelen; Graciela E Delgado; Ayse Demirkan; Francis M Finucane; Ian Ford; Melissa E Garcia; Christian Gieger; Stefan Gustafsson; Göran Hallmans; Susan E Hankinson; Aki S Havulinna; Christian Herder; Dena Hernandez; Andrew A Hicks; David J Hunter; Thomas Illig; Erik Ingelsson; Andreea Ioan-Facsinay; John-Olov Jansson; Nancy S Jenny; Marit E Jørgensen; Torben Jørgensen; Magnus Karlsson; Wolfgang Koenig; Peter Kraft; Joanneke Kwekkeboom; Tiina Laatikainen; Karl-Heinz Ladwig; Charles A LeDuc; Gordon Lowe; Yingchang Lu; Pedro Marques-Vidal; Christa Meisinger; Cristina Menni; Andrew P Morris; Richard H Myers; Satu Männistö; Mike A Nalls; Lavinia Paternoster; Annette Peters; Aruna D Pradhan; Tuomo Rankinen; Laura J Rasmussen-Torvik; Wolfgang Rathmann; Treva K Rice; J Brent Richards; Paul M Ridker; Naveed Sattar; David B Savage; Stefan Söderberg; Nicholas J Timpson; Liesbeth Vandenput; Diana van Heemst; Hae-Won Uh; Marie-Claude Vohl; Mark Walker; Heinz-Erich Wichmann; Elisabeth Widén; Andrew R Wood; Jie Yao; Tanja Zeller; Yiying Zhang; Ingrid Meulenbelt; Margreet Kloppenburg; Arne Astrup; Thorkild I A Sørensen; Mark A Sarzynski; D C Rao; Pekka Jousilahti; Erkki Vartiainen; Albert Hofman; Fernando Rivadeneira; André G Uitterlinden; Eero Kajantie; Clive Osmond; Aarno Palotie; Johan G Eriksson; Markku Heliövaara; Paul B Knekt; Seppo Koskinen; Antti Jula; Markus Perola; Risto K Huupponen; Jorma S Viikari; Mika Kähönen; Terho Lehtimäki; Olli T Raitakari; Dan Mellström; Mattias Lorentzon; Juan P Casas; Stefanie Bandinelli; Winfried März; Aaron Isaacs; Ko W van Dijk; Cornelia M van Duijn; Tamara B Harris; Claude Bouchard; Matthew A Allison; Daniel I Chasman; Claes Ohlsson; Lars Lind; Robert A Scott; Claudia Langenberg; Nicholas J Wareham; Luigi Ferrucci; Timothy M Frayling; Peter P Pramstaller; Ingrid B Borecki; Dawn M Waterworth; Sven Bergmann; Gérard Waeber; Peter Vollenweider; Henrik Vestergaard; Torben Hansen; Oluf Pedersen; Frank B Hu; P Eline Slagboom; Harald Grallert; Tim D Spector; J W Jukema; Robert J Klein; Erik E Schadt; Paul W Franks; Cecilia M Lindgren; Rudolph L Leibel; Ruth J F Loos Journal: Nat Commun Date: 2016-02-01 Impact factor: 14.919