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PNPLA3 variation prevalent in alcoholic liver disease
VIENNA — In a genome-wide association study, researchers found the PNPLA3 variation to be very prominent in alcoholic liver disease, and TM6SF2 and MBOAT7 variations as risk loci for alcoholic cirrhosis, according to data presented in the Late Breakers session at the 2015 International Liver Congress.
“This is the first [genome-wide association study] in alcoholic liver disease” or ALD, Felix Stickel, MD, department of gastroenterology and hepatology, University Hospital of Zürich, Switzerland, said during his presentation. “This confirms the pivotal role of PNPLA3 variation in the susceptibility towards ALD.”
Stickel and colleagues performed a two-stage genome-wide association study comparing patients with alcohol cirrhosis to alcohol dependent controls in Germany and the United Kingdom. In the first stage, patients recruited from Germany (410 with cirrhosis vs. 1,119 controls) and the United Kingdom (302 with cirrhosis vs. 347 controls) underwent separate genome-wide association analysis followed by meta-analysis. In the second stage, patients from Germany (521 with cirrhosis vs. 761 controls) and the United Kingdom (619 with cirrhosis vs. 160 controls). The validation cohort was predominantly male and all patients were similar in BMI and age, according to the presentation.
Researchers used Illumina BeadChips (Illumina Inc.) for genotyping and used Taqman chemistry (Applied Biosystems) for single nucleotide polymorphism replication.
According to the results, the strongest association signal in the initial meta-analysis was observed between the rs738409 variant in PNPLA3 (Pmeta=1.17×10-28. OR=2.38 [2.08-2.69]); 102 separate variants at the PNPLA3 locus associated with genome-wide significance (Pthreshold < 5×10−8).
Also, nine other independent loci provided borderline association signals (Pthreshold ≤ 1.1×10-5). Validation genotyping for rs738409 in PNPLA3 and lead markers for the top 10 associated regions confirmed disease association for rs738409 in PNPLA3, and for (MBOAT7: rs641738 Preplication = 1.35×10−4; Pcombined = 9.25×10−10; OR = 1.63 [1.46-1.80] and TM6SF2: rs10401969 Preplication = 3.29×10−5; Pcombined = 1.73×10−8; OR = 1.35 [1.25-1.44]), according to the research.
“[This study also] identifies for the first time variations TM6SF2 and MBOAT7 as risk loci for alcoholic cirrhosis,” Stickel said. – by Melinda Stevens
For More Information:
Buch S. Abstract L06. Presented at: International Liver Congress; April 22-26, 2015; Vienna.
Disclosure: The researchers report no relevant financial disclosures.